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Sample records for prognostic factors expressed

  1. Lipoprotein lipase expression is a novel prognostic factor in B-cell chronic lymphocytic leukemia.

    PubMed

    Nückel, Holger; Hüttmann, Andreas; Klein-Hitpass, Ludger; Schroers, Roland; Führer, Anja; Sellmann, Ludger; Dührsen, Ulrich; Dürig, Jan

    2006-06-01

    B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course. Recent studies have shown that expression of lipoprotein lipase (LPL) and ADAM29 may serve as novel prognostic markers in B-CLL. To investigate the prognostic value of these genes, we quantified their expression in peripheral blood mononuclear cells using quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) in a cohort of 133 B-CLL patients and correlated the results with clinical outcome, and other known prognostic factors. LPL, ADAM29, LPL and ADAM29 ratios, as well as CD38 and ZAP-70 protein expression determined by multiparameter flow cytometry, were predictive of treatment-free survival. Multivariate Cox regression analysis identified LPL, ADAM29 and CD38 as independent prognostic markers. Evaluation of several disease characteristics in association with the LPL expression status of the patients' B-CLL cells showed highly significant differences for CD38 and ZAP-70 expression, suggesting a correlation of LPL expression with these established adverse prognostic factors. Sequential RQ-PCR analyses in a subset of 22 patients revealed that LPL mRNA expression was relatively stable in the majority of patients, whereas ADAM29 expression levels varied substantially over time. Furthermore, in a subgroup analysis, LPL provided prognostic information in both early stage (Binet A) and patients with more advanced disease (Binet B and C). Conversely, high ADAM29 expression was predictive of a long treatment-free interval in Binet stage A but did not retain its prognostic significance in Binet B and C patients. The LPL/ADAM29 expression ratio was not found to be an independent prognostic factor and did not offer any advantages over the use of LPL alone. Collectively, our data confirm a role for LPL as a novel prognostic indicator in B-CLL. PMID:16840197

  2. Musashi-1 Expression is a Prognostic Factor in Ovarian Adenocarcinoma and Correlates with ALDH-1 Expression.

    PubMed

    Chen, Pu-xiang; Li, Qiao-yan; Yang, Zhulin

    2015-09-01

    The presence of cancer stem-like cells (CSCs) has been demonstrated to be associated with tumor metastasis, chemoresistance, and rapid recurrence of various tumors. The impact of CSC-related markers in the metastasis and prognosis of ovarian cancer has not been well established. In this study, the protein expression of musashi-1 and ALDH1 was measured using immunohistochemistry. Results demonstrated that the percentage of positive musashi-1 and ALDH1 expression were significantly higher in ovarian serous adenocarcinomas, mucinous adenocarcinomas and clear cell adenocarcinomas than in cystadenomas and normal tissues. The percentage of positive musashi-1 and ALDH1 expression were significantly lower in patients identified with clinical stage I or II ovarian adenocarcinomas without lymph node metastasis compared to patients with clinical stage III or IV tumors and lymph node metastasis. The expression of musashi-1 and ALDH1 was found to be highly consistent in ovarian adenocarcinomas. Univariate Kaplan-Meier analysis showed a negative correlation between musashi-1 or ALDH1 expression and overall survival. Multivariate Cox regression analysis showed that positive expression of musashi-1 or ALDH1 in ovarian adenocarcinoma was an independent predictor of poor prognosis. Our study suggested that musashi-1 and ALDH1 expression are closely related to metastasis of ovarian adenocarcinoma. The positive expression of musashi-1 and ALDH1 might be a poor-prognostic factor of ovarian adenocarcinoma. PMID:25971681

  3. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma

    PubMed Central

    Shen, G H; Ghazizadeh, M; Kawanami, O; Shimizu, H; Jin, E; Araki, T; Sugisaki, Y

    2000-01-01

    The influence of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) on prognosis and the relationship between VEGF expression and MVD in ovarian carcinoma are not well defined. We studied VEGF expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64 malignant, 13 borderline, and 17 benign) and correlated the results with the clinicopathologic prognostic factors of the disease to clarify their significance in this disease. Assessment of VEGF mRNA isoforms by RT-PCR was also performed. Of the malignant, borderline, and benign ovarian tumours respectively, two (3%), four (31%) and 16 (94%) were negative, 31 (48%), seven (54%) and one (6%) had low expressions, and 31 (48%), two (15%) and none (0%) had high expressions of VEGF. There were significant associations between the VEGF expression and disease stage (P = 0.002), histologic grade (P = 0.0004), and patient outcome (P = 0.0002). MVD did not correlate significantly with the clinicopathologic parameters. Likewise, no correlation was found between MVD and VEGF expression. The survival of patients with high VEGF expression was significantly worse than that of patients with low and negative VEGF expression (P = 0.0004). Multivariate analysis revealed that disease stage and VEGF expression were significant and independent prognostic indicators of overall survival time (P = 0.008 and P = 0.006 respectively). These findings suggest that in conjunction with the established clinicopathologic prognostic parameters of ovarian carcinoma, VEGF expression may enhance the predictability of patients at high risk for tumour progression who are potential candidates for further aggressive therapy. © 2000 Cancer Research Campaign PMID:10901370

  4. Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

    PubMed Central

    Loncaster, J A; Cooper, R A; Logue, J P; Davidson, S E; Hunter, R D; West, C M L

    2000-01-01

    The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy. © 2000 Cancer Research Campaign PMID:10944602

  5. Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma

    PubMed Central

    2016-01-01

    Store-operated calcium (Ca2+) entry (SOCE) is the principal Ca2+ entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients’ outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.

  6. Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma.

    PubMed

    Lkhagvadorj, Sayamaa; Kim, Ji-Hee; Oh, Sung-Soo; Lee, Mi-Ra; Jung, Jae Hung; Chung, Hyun Chul; Cha, Seung-Kuy; Eom, Minseob

    2016-06-01

    Store-operated calcium (Ca(2+)) entry (SOCE) is the principal Ca(2+) entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC. PMID:27247496

  7. GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas

    PubMed Central

    Haraguchi, Toshiaki; Miyoshi, Hiroaki; Hiraoka, Koji; Yokoyama, Shintaro; Ishibashi, Yukinao; Hashiguchi, Toshihiro; Matsuda, Koutaro; Hamada, Tetsuya; Okawa, Takahiro; Shiba, Naoto; Ohshima, Koichi

    2016-01-01

    Objective Recent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients. Methods We evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases. Result GATA3-positive expression was significantly associated with a higher mitotic count (P < 0.0001). Disease-free survival (DFS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0104). Overall survival (OS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0006). GATA3-positive expression was significantly associated with shorter DFS in both univariate analysis (hazard ratio [HR], 2.719; P = 0.012) and multivariate analysis (HR, 2.711; P = 0.014). GATA3-positive expression was also significantly associated with worse OS in both univariate analysis (HR, 5.730; P = 0.0007) and multivariate analysis (HR, 5.789; P = 0.0008). Conclusion These results indicate that GATA3 is an independent prognostic factor and suggest that evaluation of GATA3 expression might enable more effective clinical follow-up using prognostic stratification of STS patients. PMID:27249072

  8. Prognostic significance of inflammatory factors expression by stroma from breast carcinomas.

    PubMed

    Fernandez-Garcia, Belen; Eiro, Noemi; Miranda, Maria-Angeles; Cid, Sandra; González, Luis O; Domínguez, Francisco; Vizoso, Francisco J

    2016-08-01

    The aim of this work was to evaluate the expression and clinical relevance of some cytokines in breast carcinomas. An immunohistochemical study using tissue arrays and specific antibodies against interleukin 1β (IL-1β), IL-6, IL-10, IL-17, interferon β (IFNβ) and nuclear factor kappa B (NFκB) was performed in 108 breast carcinomas. Most studied cytokines were mainly expressed by cancer cells but also by stromal cells as cancer-associated fibroblasts (CAFs) or mononuclear inflammatory cells (MICs). Global expression (score) of IL-1β and IL-17 was positively associated with histological grade; human epidermal growth factor receptor 2-positive tumors showed a higher global expression of IFNβ but a lower global expression of NFκB; and node-negative tumors showed a higher global expression of IL-6. High score of IL-6 was significantly associated with both longer relapse free-survival (RFS) and overall survival (OS). Moreover, the expression of IL-1β by each stromal cells (CAFs and MICs) was significantly associated with both longer RFS and OS, whereas the expression of IL-10 by these cells was significantly associated with both shorter RFS and OS. However, the combination of IL-1β, IL-6 and IL-10 expression by MICs reached an important association with prognosis and improved our previously reported prognostic signification based on the matrix metalloprotease 11 status by MICs. The combination of IL-1β, IL-6 and IL-10 expression by MICs was significant and independently associated with distant RFS in a multivariate analysis. Therefore, the combination of the expression of IL-1β, IL-6 and IL-10 may serve as promising biomarkers of MICs with prognostic significance, contributing to a better characterization of breast carcinomas microenvironment. PMID:27207649

  9. FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target.

    PubMed

    Kuda, Masaaki; Kohashi, Kenichi; Yamada, Yuichi; Maekawa, Akira; Kinoshita, Yoshiaki; Nakatsura, Tetsuya; Iwamoto, Yukihide; Taguchi, Tomoaki; Oda, Yoshinao

    2016-04-01

    The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock-down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression. PMID:26553361

  10. ATPase inhibitory factor 1 expression is an independent prognostic factor in non-small cell lung cancer

    PubMed Central

    Gao, Yi-Xing; Chen, Lu; Hu, Xu-Gang; Wu, Hai-Bo; Cui, You-Hong; Zhang, Xia; Wang, Yan; Liu, Xin-Dong; Bian, Xiu-Wu

    2016-01-01

    ATPase inhibitory factor 1 (IF1), an inhibitor of the mitochondrial H+-adenosine triphosphate (ATP) synthase, is putatively involved in tumor progression. This study aimed to evaluate the expression levels of IF1 in non-small cell lung cancer (NSCLC) and the prognostic value for the patients. IF1 protein expression levels were detected in 149 cases of NSCLC by using immunohistochemistry. Kaplan-Meier analysis showed that NSCLC patients with high expression of IF1 possessed poorer outcome than those with low expression of IF1 (P=0.007). Moreover, IF1 was also prognostic in the patients with early stages (stage I/II) (P=0.042) and low grade (grade I/II) (P=0.002). Multivariable Cox-regression analysis showed that high expression of IF1 (HR=1.67, P=0.034), tumor size (HR=1.79, P=0.001), and lymph node metastasis (HR=2.66, P=0.000) were independent indicators for NSCLC patients. In conclusion, our study demonstrated that elevated expression of IF1 may associated with lymph node metastasis of NSCLC and served as an independent prognostic and recurrent indicator for the patients. PMID:27294006

  11. Expression of mitochondrial transcription factor A in endometrial carcinomas: clinicopathologic correlations and prognostic significance.

    PubMed

    Toki, Naoyuki; Kagami, Seiji; Kurita, Tomoko; Kawagoe, Toshinori; Matsuura, Yusuke; Hachisuga, Toru; Matsuyama, Atsuji; Hashimoto, Hiroshi; Izumi, Hiroto; Kohno, Kimitoshi

    2010-04-01

    Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA. This study was conducted to elucidate the clinicopathologic and prognostic significance of mtTFA in patients with endometrial carcinoma. This study investigated the relationship between the immunohistochemical expression of mtTFA and various clinicopathological variables in 276 endometrial carcinomas, including 245 endometrioid adenocarcinomas and 31 nonendometrioid carcinomas (21 serous carcinomas and 10 clear cell adenocarcinomas). Both uni- and multivariate regression analyses were performed. The mtTFA labeling index of endometrioid adenocarcinomas ranged from 0% to 98%, with a median value of 32%, which was selected as the cut-off point for mtTFA expression. The mtTFA expression in endometrioid adenocarcinomas was significantly associated with the surgical stage, myometrial invasion, lymphovascular space invasion, cervical invasion, and lymph node metastasis. In contrast, no correlation between clinicopathologic variables and mtTFA expression was found in nonendometrioid carcinomas. Correlation analysis between mtTFA and p53 expression by using the Pearson test showed significant correlation in endometrioid adenocarcinomas (P = 0.007), but no significant correlation in nonendometrioid carcinomas (P = 0.947). A univariate survival analysis showed that the 10-year overall survival rate of the patients with mtTFA-positive endometrioid adenocarcinoma was significantly worse than that of patients with mtTFA-negative endometrioid adenocarcinoma (80.8% vs. 93.8%, P = 0.012). However, the multivariate analysis revealed that mtTFA expression in endometrioid adenocarcinomas was no independent prognostic factor. The positive mtTFA expression is a useful maker for progression of the tumors and the poor prognosis of the patients in endometrioid adenocarcinomas. PMID:20232213

  12. CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer.

    PubMed

    Stanisavljević, Luka; Aßmus, Jörg; Storli, Kristian Eeg; Leh, Sabine Maria; Dahl, Olav; Myklebust, Mette Pernille

    2016-06-01

    The CXCL12-CXCR4 axis is proposed to mediate metastasis formation. In this study, we examined CXCL12, CXCR4 and the relative CXCL12-CXCR4 expression as prognostic factors in two cohorts of colon cancer patients. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to study CXCR4, CXCL12 and relative CXCL12-CXCR4 expression in tissue microarrays. Our study included totally 596 patients, 290 in cohort 1 and 306 in cohort 2. For tumour, node, metastasis (TNM) stage III, low nuclear expression of CXCR4 was a positive prognostic factor for 5-year disease-free survival (DFS) in cohort 1 (P = 0.007) and cohort 2 (P = 0.023). In multivariate analysis for stage III, nuclear expression of CXCR4 in cohort 1 was confirmed as a prognostic factor for DFS (hazard ratio (HR), 0.27; 95 % CI, 0.09 to 0.77). For TNM stage III, high cytoplasmic expression of CXCL12 was associated with better 5-year DFS in both cohorts (P = 0.006 and P = 0.006, respectively). We further validated the positive prognostic value of CXCL12 expression for 5-year DFS in stage III with ISH (P = 0.022). For TNM stage III, the relative CXCL12-CXCR4 expression (CXCL12 > CXCR4 vs CXCL12 = CXCR4 vs CXCL12 < CXCR4) was a prognostic factor for 5-year DFS in cohort 1 (92 % vs 46 % vs 31 %, respectively; P < 0.001) and cohort 2 (92 % vs 66 % vs 30 %, respectively; P = 0.006). In conclusion, CXCL12 and relative CXCL12-CXCR4 expression are independent prognostic factors for 5-year DFS in TNM stage III colon cancer. PMID:26678887

  13. Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

    PubMed

    Grange, Florent; Petrella, Tony; Beylot-Barry, Marie; Joly, Pascal; D'Incan, Michel; Delaunay, Michele; Machet, Laurent; Avril, Marie-Francoise; Dalac, Sophie; Bernard, Philippe; Carlotti, Agnes; Esteve, Eric; Vergier, Beatrice; Dechelotte, Pierre; Cassagnau, Elisabeth; Courville, Philippe; Saiag, Philippe; Laroche, Liliane; Bagot, Martine; Wechsler, Janine

    2004-05-15

    Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions. PMID:14726400

  14. Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

    PubMed Central

    Chang, Yuan; Niu, Wei; Lian, Pei-Long; Wang, Xian-Qiang; Meng, Zhi-Xin; Liu, Yi; Zhao, Rui

    2016-01-01

    AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor (VEGF) and prognosis in gastric cancer. METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density (MVD) (endocan-MVD), VEGF and vascular endothelial growth factor receptor 2 (VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student’s t-test or an analysis of variance test. Spearman’s rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. Long-term survival of these patients was analysed using univariate and multivariate analyses. RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues (108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type (P > 0.05), while endocan-MVD was associated with tumour size, Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage (P < 0.05). According to the Spearman’s rank correlation analysis, endocan-MVD had a positive correlation with VEGF (r = 0.167, P = 0.047) and VEGFR2 (r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD (17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor. CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer. PMID:27340359

  15. MUC1 Immunohistochemical Expression as a Prognostic Factor in Gastric Cancer: Meta-Analysis

    PubMed Central

    Wang, Xiao-Tong; Kong, Fan-Biao; Mai, Wei; Li, Lei; Pang, Li-Ming

    2016-01-01

    MUC1, a member of the mucin family, is expressed in tumors of various human organs and may function as an antiadhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis, and served as a potential biomarker of tumor progression in early gastric cancer. However, its prognostic significance in gastric cancer is still in dispute. We performed a meta-analysis to evaluate the relationship between MUC1 expression and prognosis of gastric cancer. A total of ten eligible studies with 834 cases and 548 controls were included. MUC1 positive cases were highly positive in intestinal-type carcinomas (OR = 1.76, 95% CI: 1.27–2.44, P = 0.0008 fixed-effect), higher rate of vascular invasion (OR = 1.64, 95% CI: 1.13–2.39, P = 0.009 fixed-effect), and lymph node metastasis (OR = 2.10, 95% CI: 1.20–3.67, P = 0.01 random-effect), as well as lower 5-year survival rate (HR = 0.27, 95% CI: 0.11–0.66, P = 0.004 random-effect). However, the presence of MUC1 was not associated with gender, tumor size, histologic differentiation, and clinical stage. In summary, MUC1 is a prognostic factor in gastric cancer, which acts as a marker of poor outcome in patients with gastric cancer. Further clinical studies are needed to confirm the role of MUC1 in clinical practice. PMID:27190429

  16. CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor.

    PubMed

    Roncella, Silvio; Laurent, Stefania; Fontana, Vincenzo; Ferro, Paola; Franceschini, Maria Cristiana; Salvi, Sandra; Varesano, Serena; Boccardo, Simona; Vigani, Antonella; Morabito, Anna; Canessa, Pier Aldo; Giannoni, Ugo; Rosenberg, Ilan; Valentino, Alessandro; Fedeli, Franco; Merlo, Domenico Franco; Ceppi, Marcello; Riggio, Salvatore; Romani, Massimo; Saverino, Daniele; Poggi, Alessandro; Pistillo, Maria Pia

    2016-08-01

    CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18-0.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients. PMID:27207606

  17. Prognostic Significance of Hypoxia-Inducible Factor Expression in Renal Cell Carcinoma

    PubMed Central

    Fan, Yang; Li, Hongzhao; Ma, Xin; Gao, Yu; Chen, Luyao; Li, Xintao; Bao, Xu; Du, Qingshan; Zhang, Yu; Zhang, Xu

    2015-01-01

    Abstract The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis. PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1α or HIF-2α detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed. A total of 14 studies composed of 1258 patients for HIF-1α evaluation and 619 patients for HIF-2α evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1α expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898–2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595–2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675–1.836, P = 0.674). Similarly, HIF-2α expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667–3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566–1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1α was significantly associated with poor OS (HR 2.014, 95% CI 1.206–3.363, P = 0.007) and the high cytoplasmic expression of HIF -2α was significantly associated with poor CSS (HR 2.356, 95% CI 1.629–3.407, P = 0.000). The increased nuclear expression of HIF-1α and cytoplasmic expression of HIF-2α indicate unfavorable prognosis in RCC patients, which

  18. Stromal Palladin Expression Is an Independent Prognostic Factor in Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Sato, Daisuke; Tsuchikawa, Takahiro; Mitsuhashi, Tomoko; Hatanaka, Yutaka; Marukawa, Katsuji; Morooka, Asami; Nakamura, Toru; Shichinohe, Toshiaki; Matsuno, Yoshihiro; Hirano, Satoshi

    2016-01-01

    It has been clear that cancer-associated fibroblasts (CAFs) in the tumor microenvironment play an important role in pancreatic ductal adenocarcinoma (PDAC) progression. However, how CAFs relate to the patients’ prognosis and the effects of chemoradiation therapy (CRT) has not been fully investigated. Tissue microarrays (TMAs) representing 167 resected PDACs without preoperative treatment were used for immunohistochemical studies (IHC) of palladin, α-smooth muscle actin (SMA), and podoplanin. Correlations between the expression levels of these markers and clinicopathological findings were analyzed statistically. Whole sections of surgical specimens from PDACs with and without preoperative CRT, designated as the chemotherapy-first group (CF, n = 19) and the surgery-first group (SF, n = 21), respectively, were also analyzed by IHC. In TMAs, the disease-specific survival rate (DSS) at 5 years for all 167 cases was 23.1%. Seventy cases (41.9%) were positive for palladin and had significantly lower DSS (p = 0.0430). α-SMA and podoplanin were positive in 167 cases (100%) and 131 cases (78.4%), respectively, and they were not significantly associated with DSS. On multivariable analysis, palladin expression was an independent poor prognostic factor (p = 0.0243, risk ratio 1.60). In the whole section study, palladin positivity was significantly lower (p = 0.0037) in the CF group (5/19) with a significantly better DSS (p = 0.0144) than in the SF group (16/22), suggesting that stromal palladin expression is a surrogate indicator of the treatment effect after chemoradiation therapy. PMID:27023252

  19. Positive cyclin T expression as a favorable prognostic factor in treating gastric gastrointestinal stromal tumors

    PubMed Central

    LIN, LIEN-FU; JIN, JONG-SHIAW; CHEN, JUI-CHANG; HUANG, CHIA-CHI; SHEU, JENG-HORNG; CHEN, WENLUNG; TSAO, TANG-YI; HSU, CHIH-WEI

    2016-01-01

    Positive transcriptional elongation factor b (P-TEFb) contains the catalytic subunit cyclin-dependent kinase 9 (Cdk9) and the regulatory subunit cyclin T. Cyclin T1 and Cdk9 are the key factors of the PTEFb pathways and are overexpressed in the human head and neck carcinoma cell line. However, there have been limited studies regarding the role of cyclin T1 and Cdk9 in gastric gastrointestinal stromal tumors (GISTs). The aim of the present study was to assess the association between cyclin T1 and Cdk9 and their clinical significance in gastric GISTs. A total of 30 gastric GIST patients who underwent either laparoscopic or laparotomic partial gastrectomy were enrolled in the study. The surgical tissue slides were stained with Cdk9 and cyclin T1 antibodies, and the immunohistochemistry scores and disease-free survival (DFS) were analyzed. Ten patients were cyclin T1-positive, and 20 were negative. All 11 patients with recurrent tumors or distant metastases were cyclin T1-negative patients. Old age, large tumor size, a high Ki67 IHC staining score, high mitotic count and negative cyclin T1 staining revealed a worse clinical outcome in univariate analysis. By contrast, the Cdk9 score was not associated with clinical parameters. The Kaplan-Meier survival curve illustrated that the DFS rate of the patients with negative cyclin T1 staining was significantly lower than that of the patients with positive cyclin T1 staining. Positive expression of cyclin T1 was a good prognostic factor in patients with gastric GISTs. PMID:27284431

  20. Clinicopathological Differences and Prognostic Value of Hypoxia-Inducible Factor-2α Expression for Gastric Cancer

    PubMed Central

    Zheng, Fangchao; Du, Feng; Zhao, Jiuda

    2016-01-01

    Abstract Published literatures have reported the relationship between hypoxic-inducible factor-2α (HIF-2α) expression and clinicopathological features in gastric cancer (GC), but the evaluated conclusions remain controversial. A meta-analysis was carried to examine the clinicopathological features and prognostic values of HIF-2α in patients with GC. Systematic detailed searches were performed to Pub Med, Cochrane Library, and EBSCO until to August 2015. Six studies (508 specimens) were included in this meta-analysis. HIF-2α-positive expression indicates an unfavorable prognosis value and advanced clinicopathological differences for the available patient dates with GC. Further multivariate meta-analysis revealed that HIF-2α-positive expression in gastric cancer associated with deeper tumor infiltration (OR = 3.08; 95%CI: 1.18–8.04), higher rates of lymphatic metastasis (OR = 3.26; 95%CI: 1.10–9.63), higher TNM stage (III+IV) (OR = 2.61; 95%CI: 1.40–4.84), and much lower 5-year overall survival (OR = 2.08; 95%CI: 1.21–3.58). Nevertheless, there is no association between HIF-2α-positive expression and worse tumor differentiation (OR = 2.03; 95%CI: 0.73–5.64). In addition, by this subgroup analysis, HIF-2α-positive expression associated with deeper tumor infiltration (OR = 3.81; 95%CI: 1.03–14.08), higher lymphatic metastasis (OR = 4.71; 95%CI: 1.08–20.50), higher TNM stage (OR = 3.21; 95%CI: 1.57–6.57), worse tumor differentiation (OR = 3.08; 95%CI: 1.51–6.31), and lower 5-year overall survival (OR = 2.34; 95%CI: 1.15–4.79). Our results indicate that HIF-2α overexpression can potently predict the poor prognosis and may be a potential therapeutic target for gastric carcinoma, according to the limited evidence. Meanwhile, further studies are needed to elucidate the accuracy of these results. PMID:26886654

  1. Cathepsin S expression: An independent prognostic factor in glioblastoma tumours--A pilot study.

    PubMed

    Flannery, Thomas; McQuaid, Stephen; McGoohan, Caroline; McConnell, Robert S; McGregor, Gordon; Mirakhur, Meenakshi; Hamilton, Peter; Diamond, James; Cran, Gordon; Walker, Brian; Scott, Christopher; Martin, Lorraine; Ellison, David; Patel, Chirag; Nicholson, Clare; Mendelow, David; McCormick, Derek; Johnston, Patrick G

    2006-08-15

    Cysteine proteinases have been implicated in astrocytoma invasion. We recently demonstrated that cathepsin S (CatS) expression is up-regulated in astrocytomas and provided evidence for a potential role in astrocytoma invasion (Flannery et al., Am J Path 2003;163(1):175-82). We aimed to evaluate the significance of CatS in human astrocytoma progression and as a prognostic marker. Frozen tissue homogenates from 71 patients with astrocytomas and 3 normal brain specimens were subjected to ELISA analyses. Immunohistochemical analysis of CatS expression was performed on 126 paraffin-embedded tumour samples. Fifty-one astrocytoma cases were suitable for both frozen tissue and paraffin tissue analysis. ELISA revealed minimal expression of CatS in normal brain homogenates. CatS expression was increased in grade IV tumours whereas astrocytoma grades I-III exhibited lower values. Immunohistochemical analysis revealed a similar pattern of expression. Moreover, high-CatS immunohistochemical scores in glioblastomas were associated with significantly shorter survival (10 vs. 5 months, p = 0.014). With forced inclusion of patient age, radiation dose and Karnofsky score in the Cox multivariate model, CatS score was found to be an independent predictor of survival. CatS expression in astrocytomas is associated with tumour progression and poor outcome in glioblastomas. CatS may serve as a useful prognostic indicator and potential target for anti-invasive therapy. PMID:16550604

  2. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1, 2 and 3 in Periampullary Adenocarcinoma

    PubMed Central

    Heby, Margareta; Warfvinge, Carl Fredrik; Nodin, Björn; Eberhard, Jakob; Jirström, Karin

    2016-01-01

    Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumours with dismal prognosis, for which there is an urgent need to identify novel treatment strategies. The human epithelial growth factor receptors EGFR, HER2 and HER3 have been studied in several tumour types, and HER-targeting drugs have a beneficial effect on survival in selected types of cancer. However, these effects have not been evident in pancreatic cancer, and remain unexplored in other types of periampullary cancer. The prognostic impact of HER-expression in these cancers also remains unclear. The aim of this study was therefore to examine the expression and prognostic value of EGFR, HER2 and HER3 in periampullary cancer, with particular reference to histological subtype. To this end, protein expression of EGFR, HER2 and HER3, and HER2 gene amplification was assessed by immunohistochemistry and silver in situ hybridization, respectively, on tissue microarrays with tumours from 175 periampullary adenocarcinomas, with follow-up data on recurrence-free survival (RFS) and overall survival (OS) for up to 5 years. EGFR expression was similar in pancreatobiliary (PB) and intestinal (I) type tumours, but high HER2 and HER3 expression was significantly more common in I-type tumours. In PB-type cases receiving adjuvant gemcitabine, but not in untreated cases, high EGFR expression was significantly associated with a shorter OS and RFS, with a significant treatment interaction in relation to OS (pinteraction = 0.042). In I-type cases, high EGFR expression was associated with a shorter OS and RFS in univariable, but not in multivariable, analysis. High HER3 expression was associated with a prolonged RFS in univariable, but not in multivariable, analysis. Neither HER2 protein expression nor gene amplification was prognostic. The finding of a potential interaction between the expression of EGFR and response to adjuvant chemotherapy in PB-type tumours needs validation, and merits

  3. Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

    PubMed

    Laurinavicius, Arvydas; Plancoulaine, Benoit; Rasmusson, Allan; Besusparis, Justinas; Augulis, Renaldas; Meskauskas, Raimundas; Herlin, Paulette; Laurinaviciene, Aida; Abdelhadi Muftah, Abir A; Miligy, Islam; Aleskandarany, Mohammed; Rakha, Emad A; Green, Andrew R; Ellis, Ian O

    2016-04-01

    Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity. PMID:26818835

  4. Prognostic Significance of Tumor Hypoxia Inducible Factor-1{alpha} Expression for Outcome After Radiotherapy in Oropharyngeal Cancer

    SciTech Connect

    Silva, Priyamal; Slevin, Nick J.; Sloan, Philip; Valentine, Helen; Cresswell, Jo; Ryder, David; Price, Patricia; Homer, Jarrod J.; West, Catharine

    2008-12-01

    Purpose: Head-and-neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of patients in terms of subsite, treatment, and biology. Currently most management decisions are based on clinical parameters with little appreciation of patient differences in underlying tumor biology. We investigated the prognostic significance of clinicopathologic features and tumor hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) expression in a homogeneous series of patients who underwent radiotherapy. Methods and Materials: An audit identified 133 consecutive patients with histologically proven squamous cell carcinoma of the tonsil or tongue base. All patients received primary radiotherapy between 1996 and 2001. Tumor HIF-1{alpha} expression was examined in 79 patients. Results: Features associated with poor locoregional control were low Hb level (p = 0.05) and advancing T (p = 0.008), N (p = 0.03), and disease (p = 0.008) stage. HIF-1{alpha} expression was a more significant adverse prognostic factor in the tonsil (hazard ratio [HR], 23.1; 95% confidence interval [CI]. 3.04-176.7) than the tongue-base tumor (HR, 2.86; 95% CI, 1.14-7.19) group (p = 0.03, test for interaction). High tumor HIF-1{alpha} expression was associated with low blood Hb levels (p = 0.03). In a multivariate analysis HIF-1{alpha} expression retained prognostic significance for locoregional control (HR, 7.10; 95% CI, 3.07-16.43) and cancer-specific survival (HR, 9.19; 95% CI, 3.90-21.6). Conclusions: There are significant differences in radiation therapy outcome within a homogeneous subsite of the oropharynx related to molecular marker expression. The work highlights the importance of studying homogeneous groups of patients in HNSCC, and the complex interrelationships between tumor biology and clinicopathologic factors. The establishment of tumor-type specific markers would represent a major advance in this area.

  5. MicroRNA-155 expression as a prognostic factor in patients with gallbladder carcinoma after surgical resection

    PubMed Central

    Zhang, Xue-Lin; Chen, Jun-Hong; Qin, Cheng-Kun

    2015-01-01

    Background: MicroRNA-155 (miR-155) is over-expressed in both hematopoietic malignancies and solid tumors. In the present study, we investigated the clinical significance of miR-155 in gallbladder carcinoma among Chinese population. Methods: Tissue specimens were collected from 133 patients who had undergone surgical resection at Shandong Provincial Hospital, Shandong University between May 2008 and April 2014. We profiled miR- 155 expression in the gallbladder carcinoma tissues and normal gallbladder tissues by qRT-PCR. The Kaplan-Meier method was used to analyze the 5-year survival rate. Results: The expression levels of miR-155 were significantly higher in gallbladder carcinoma tissues than that in normal gallbladder tissues (P<0.001). High miR-155 expression was significantly associated with TNM stage (P=0.003), lymph node status (P=0.042), liver metastasis (P=0.010), and differentiated degree (P<0.001). We found that gallbladder carcinoma patients with high miR-155 expression level had distinctly shorter overall survival than patients with low miR-155 expression level (P=0.03). Multivariate analysis revealed that miR-155 expression level was independent prognostic factors for overall survival (HR=2.394, 95% CI: 1.568-10.034; P=0.009). Conclusion: High miR-155 expression is a prognostic indicator for poor prognosis of patients with gallbladder carcinoma among Chinese population. PMID:26885061

  6. RBX1 expression is an unfavorable prognostic factor in patients with non-small cell lung cancer.

    PubMed

    Xing, Rui; Chen, Kuan-Bing; Xuan, Ying; Feng, Chi; Xue, Ming; Zeng, Yue-Can

    2016-09-01

    The purpose of this study was to assess the prognostic value of RBX1 in patients with non-small cell lung cancer (NSCLC). Quantitative real-time (RT-PCR) and western blot were used to evaluate the mRNA and protein expression of RBX1 in NSCLC and corresponding non-cancerous tissues. Immunohistochemistry was performed to examine the expression of RBX1 in 192 NSCLC tissue samples. Overall survival was evaluated by the Kaplan-Meier method and analyzed by the log-rank test between different groups. The results showed that the RBX1 expression was significantly higher in NSCLC tissues than the corresponding non-cancerous lung tissues. High RBX1 expression was related to poor tumor differentiation, advanced TNM stage, and lymph node metastasis. Patients with high RBX1 expression had poor overall survival than those with high expression levels, which was consistent with the results of the subgroup analysis. Multivariate analysis showed that high RBX1 expression was an unfavorable prognostic factor for NSCLC patients. Our study indicated that RBX1 might play an important role in the observation of prognosis in NSCLC and could be a valuable marker for predicting the treatment outcome in patients with NSCLC. PMID:27566015

  7. Sestrin2 expression is a favorable prognostic factor in patients with non-small cell lung cancer

    PubMed Central

    Chen, Kuan-Bing; Xuan, Ying; Shi, Wen-Jun; Chi, Feng; Xing, Rui; Zeng, Yue-Can

    2016-01-01

    The purpose of this study was to evaluate the prognostic value of Sestirn2 in patients with non-small cell lung cancer (NSCLC). Quantitative real-time ( RT-PCR) and western blot were performed to investigate the mRNA and protein expression of Sestirn2 in NSCLC and corresponding non-cancerous tissues. Immunohistochemistry was used to detect the expression of Sestirn2 in 210 NSCLC tissue samples. Overall survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test between different groups. The results indicated that the Sestirn2 expression was significantly lower in NSCLC tissues than the corresponding non-cancerous lung tissues. Low Sestirn2 expression was related to poor tumor differentiation, advanced TNM stage, and lymph node metastasis. Patients with high Sestirn2 expression had longer overall survival than those with low expression levels, which was consistent with the results of the subgroup analysis. Multivariate analysis showed that high Sestirn2 expression was a favorable prognostic factor for NSCLC patients. Our study indicated that Sestirn2 could play an important role in the observation of prognosis in NSCLC and might be a valuable marker for predicting the treatment outcome in patients with NSCLC. PMID:27186314

  8. Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts

    PubMed Central

    Ono, Takaaki; Takeshita, Akihiro; Kishimoto, Yuji; Kiyoi, Hitoshi; Okada, Masaya; Yamauchi, Takahiro; Emi, Nobuhiko; Horikawa, Kentaro; Matsuda, Mitsuhiro; Shinagawa, Katsuji; Monma, Fumihiko; Ohtake, Shigeki; Nakaseko, Chiaki; Takahashi, Masatomo; Kimura, Yukihiko; Iwanaga, Masako; Asou, Norio; Naoe, Tomoki

    2014-01-01

    Expression of CD56 has recently been introduced as one of the adverse prognostic factors in acute promyelocytic leukemia (APL). However, the clinical significance of CD56 antigen in APL has not been well elucidated. We assessed the clinical significance of CD56 antigen in 239 APL patients prospectively treated with all-trans retinoic acid and chemotherapy according to the Japan Adult Leukemia Study Group APL97 protocol. All patients were prospectively treated by the Japan Adult Leukemia Study Group APL97 protocol. The median follow-up period was 8.5 years. Positive CD56 expression was found in 23 APL patients (9.6%). Expression of CD56 was significantly associated with lower platelet count (P = 0.04), severe disseminated intravascular coagulation (P = 0.04), and coexpression of CD2 (P = 0.03), CD7 (P = 0.04), CD34 (P < 0.01) and/or human leukocyte antigen-DR (P < 0.01). Complete remission rate and overall survival were not different between the two groups. However, cumulative incidence of relapse and event-free survival (EFS) showed an inferior trend in CD56+ APL (P = 0.08 and P = 0.08, respectively). Among patients with initial white blood cell counts of 3.0 × 109/L or more, EFS and cumulative incidence of relapse in CD56+ APL were significantly worse (30.8% vs 63.6%, P = 0.008, and 53.8% vs 28.9%, P = 0.03, respectively), and in multivariate analysis, CD56 expression was an unfavorable prognostic factor for EFS (P = 0.04). In conclusion, for APL with higher initial white blood cell counts, CD56 expression should be regarded as an unfavorable prognostic factor. PMID:24206578

  9. Prognostic value of vascularity and vascular endothelial growth factor expression in non-small cell lung cancer

    PubMed Central

    Baillie, R; Carlile, J; Pendleton, N; Schor, A

    2001-01-01

    Aims—High expression of the angiogenic factor vascular endothelial growth factor (VEGF) in tumours has been found to be associated with poor prognosis in some studies, but not in others. The aims of this study were to determine the prognostic value of VEGF in operable non-small cell lung cancer (NSCLC) and its possible association with vascularity. Methods—Sections from 81 NSCLC archival specimens were stained with antibodies to von Willebrand factor (vWF) and VEGF. Vascularity was measured by the average density of vWF positive vessels. VEGF expression in tumour cells was assessed by consensus of two independent observers according to three indices, namely: (1) percentage of area stained, (2) intensity of staining, and (3) final score (product of area and intensity). Results—VEGF immunoreactivity was present in all tumours and adjacent normal lung tissue. None of the three VEGF indices was associated with vascularity or the clinical parameters examined. Mean survival times were shorter in patients with high VEGF expression, but the difference was not significant. This applied to the full cohort of patients, or when analysed separately according to tumour type or stage. However, high VEGF expression was associated with poor survival in patients with high vascularity (p = 0.02). VEGF had no discriminant value among patients with low vascularity. Vascularity had no prognostic value, except for late stage patients (UICC stages II and IIIa combined; n = 36), where high vascularity was associated with longer survival (p = 0.01). Conclusions—VEGF on its own has no prognostic value in NSCLC, but may become a useful indicator when combined with vascularity. VEGF may play a physiological role in the normal lung. Key Words: non-small cell lung cancer • vascular endothelial growth factor • vascularity • prognosis PMID:11215279

  10. Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy

    SciTech Connect

    Fraunholz, Ingeborg; Falk, Stefan

    2013-08-01

    Purpose: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Methods and Materials: Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Results: EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients’ sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). Conclusion: Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.

  11. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma

    PubMed Central

    Hedner, Charlotta; Borg, David; Nodin, Björn; Karnevi, Emelie; Jirström, Karin; Eberhard, Jakob

    2016-01-01

    Background Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma. Methods Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology. Results and Discussion High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods. PMID:26844548

  12. Expression of vascular endothelial growth factor (VEGF) in locally invasive prostate cancer is prognostic for radiotherapy outcome

    SciTech Connect

    Green, Melanie M.L.; Hiley, Crispin T.; Shanks, Jonathan H.; Bottomley, Ian C.; West, Catharine; Cowan, Richard A.; Stratford, Ian J. . E-mail: ian.j.stratford@manchester.ac.uk

    2007-01-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important hypoxia-inducible pro-angiogenic protein that has been linked with an adverse survival outcome after radiotherapy in other cancer types: we hypothesized that this may also occur in prostate cancer. A retrospective study was, therefore, carried out to evaluate the potential of tumor VEGF expression to predict radiotherapy outcome in patients with high-risk prostate cancer. Methods and Materials: Fifty patients with locally advanced (T3 N0 M0) tumors of Gleason score {>=}6, and who received radiotherapy alone as primary treatment for their disease, were studied. Vascular endothelial growth factor expression was assessed on pretreatment diagnostic tumor biopsies using a semiquantitative immunohistochemical scoring system. The results were analyzed in relation to clinicopathologic factors and patient outcome including biochemical failure and disease-specific mortality. Results: High VEGF expression was associated with a poor prognosis: in univariate log rank analysis, VEGF was the only significant prognostic factor for disease-specific survival (p = 0.035). High VEGF expression also associated with increased Gleason score (p = 0.02), but not posttreatment biochemical failure. Conclusion: High tumor expression of VEGF identified patients at high risk of failure of treatment with radiotherapy. These patients might benefit from additional treatment approaches incorporating anti-angiogenic or hypoxia-specific agents.

  13. The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer.

    PubMed Central

    Bartlett, J. M.; Langdon, S. P.; Simpson, B. J.; Stewart, M.; Katsaros, D.; Sismondi, P.; Love, S.; Scott, W. N.; Williams, A. R.; Lessells, A. M.; Macleod, K. G.; Smyth, J. F.; Miller, W. R.

    1996-01-01

    The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-alpha (P = 1.00). EGF receptor mRNA expression was significantly and positively associated with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor TGF-alpha showed any link with histological subtype or stage. The survival of patients with malignant tumours possessing EGF receptor mRNA was significantly reduced compared with that of patients whose tumours were negative (P = 0.030 for all malignant tumours; P = 0.007 for malignant epithelial tumours only). In contrast, neither the expression of TGF-alpha nor EGF was related to survival. These data suggest that the presence of EGF receptor mRNA is associated with poor prognosis in primary ovarian cancer. Images Figure 1 PMID:8562334

  14. URG4 expression is a novel prognostic factor for the progression of nasopharyngeal carcinoma and overall survival of patient

    PubMed Central

    Yu, Guodong; Meng, Qingxiang; Zhang, Tian; Zeng, Chen; He, Benfu; Zhang, Shanshan

    2016-01-01

    URG4, a novel oncogene, is involved in the development and progression of various tumors. This study investigated the clinicopathological significance of URG4 in nasopharyngeal carcinoma (NPC). We used five NPC tissues and adjacent normal nasopharyngeal tissues to determine URG4 expression and found that URG4 was upregulated in NPC tissues. Immunohistochemistry analysis found URG4 was expressed positively in 97.1% (99/102) of NPC samples and highly expressed in 41.2% (42/102) of NPC samples. Its level was positively correlated with advancing clinical stage. Kaplan–Meier analysis with the log-rank test found that patients with high URG4 expression had poor outcome and patients with low URG4 expression had better survival. Statistical analysis showed that there was a significant correlation between URG4 expression and clinical stage, larger tumor size, and lymph node involvement. Cox-regression analysis showed that URG4 expression could serve as a prognostic factor for NPC patients. In summary, this study showed that URG4 was upregulated in NPC tissues, patients with high URG4 expression had poor outcome, and URG4 was found to be a valuable biomarker for NPC progression. PMID:27284257

  15. Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors

    PubMed Central

    Damiani, Daniela; Tiribelli, Mario; Raspadori, Donatella; Sirianni, Santina; Meneghel, Alessia; Cavalllin, Margherita; Michelutti, Angela; Toffoletti, Eleonora; Geromin, Antonella; Simeone, Erica; Bocchia, Monica; Fanin, Renato

    2015-01-01

    CD200, a protein belonging to the immunoglobulin superfamily, has been associated with a poor prognosis in lymphoproliferative disorders and in acute leukemia. We studied the expression of CD200 in a series of 244 patients with diagnosis of acute myeloid leukemia (AML), to evaluate its impact on outcome and its possible association with other known prognostic factors. CD200 was found in 136/244 (56%) patients, in 41 of whom (30%) with high intensity of expression (MFI ≥ 11). CD200 was more frequent in secondary compared to de novo leukemia (p = 0.0006), in CD34 positive cases (p = 0.00001), in Bcl2 overexpressing cases (p = 0.01), in those wild-type Flt3 (p = 0.004) and with favorable or unfavorable compared to intermediate karyotype (p = 0.0003). CD200+ patients have a two-fold lower probability to attain complete remission, both in univariate (p = 0.006) and multivariate (p = 0.04) analysis. The negative impact of CD200 was found also in overall survival (p = 0.02) and was correlated with the intensity of expression of the molecule (p = 0.024). CD200 has an additive negative impact on survival in patients with unfavorable cytogenetic (p = 0.046) and in secondary leukemia (p = 0.05), and is associate with a worsening of outcome in patients with favorable biological markers, such as mutated NPM (p = 0.02), wild-type Flt3 (p = 0.034), negativity of CD34 (p = 0.03) and of CD56 (p = 0.03). In conclusion, CD200 is emerging as both a prognostic factor and a potential target of novel therapeutic approaches for AML, aiming to reverse the “do not eat me” signal of CD200 or to manipulate the suppressive immune microenvironment induced by CD200 binding to its receptor. PMID:26338961

  16. The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

    PubMed Central

    Dvořák, Josef; Urbanec, Marek; Bluml, Antonin; Čermáková, Eva; Bartoš, Jiří; Petera, Jiří

    2015-01-01

    Aim of the study The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Material and methods Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m2 in two daily oral administrations. Surgery was indicated 4–8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. Results All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed. Conclusions The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival. PMID:26199571

  17. MAGE-A3 expression is an adverse prognostic factor in diffuse large B-cell lymphoma.

    PubMed

    Olarte, Irma; Martinez, Adolfo; Ramos-Peñafiel, Christian; Castellanos-Sinco, Humberto; Zamora, Jorge; Collazo-Jaloma, Juan; Gutiérrez, Mario; Gutiérrez-Kobeh, Laila; Chavez-Olmos, Pedro; Manzanilla, Hugo; Garrido-Guerrero, Efraín; Ordoñez-Razo, Rosa M; Miranda, Enrique I

    2011-11-01

    This study evaluates the prognostic value of MAGE-A3 expression in 28 diffuse large B-cell lymphoma (DLBCL) patients. A significant association was observed between MAGE-A3 expressions, assessed by quantitative real-time RT-polymerase chain reaction (PCR), with advanced stages of disease (P < 0.05). Elevated serum lactate dehydrogenase (LDH) levels and International Prognostic Index (IPI) score were significantly higher in MAGE-A3-positive patients (P = 0.025 and P = 0.004, respectively). Expression of MAGE-A3 was associated with poor response to treatment and a significantly shorter overall survival (P < 0.001). Our data address new information in the association of MAGE-A3 expression and poor prognosis in DLBCL patients. PMID:22183072

  18. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  19. GLI1 expression is an important prognostic factor that contributes to the poor prognosis of rhabdomyosarcoma.

    PubMed

    Wang, Yuanyuan; Sun, Chao; Jiang, Jinfang; Xie, Yuwen; Li, Bingcheng; Cui, Xiaobin; Chen, Yunzhao; Liu, Chunxia; Li, Feng

    2016-03-01

    The GLI1 and MDM2 genes are amplified or exhibit copy number gains in rhabdomyosarcoma (RMS). Here, we used immunohistochemistry to determine the relationships between GLI1 and MDM2 protein expression and several clinicopathological variables of RMS. GLI1 and MDM2-positivity rates were 61.36% and 13.64%, respectively. GLI1 expression correlated with presence of the PAX3-FOXO1 fusion gene (P=0.040) and lymph node metastasis (P=0.034), and a significant association was found between GLI1 expression and overall survival (OS) (P=0.008). However, there was no association between MDM2 expression and any of the clinicopathological parameters or OS. Thus, GLI1 may be a biomarker of poor prognosis in RMS patients, and could itself be a therapeutic target. This contrasts with the apparent lack of clinical importance of MDM2 in RMS pathology, at least in the cohorts we examined. PMID:26544916

  20. Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resistance to docetaxel

    PubMed Central

    2013-01-01

    Background Forkhead box transcription factor 1 (FOXM1) has been reported to overexpress and correlate with pathogenesis in a variety of human malignancies. However, little research has been done to investigate its clinical significance in gastric cancer. Methods We examined the expression of FOXM1 in 103 postoperational gastric cancer tissues and 5 gastric cell lines by immunohistochemistry and western blot analysis respectively. Data on clinic-pathological features and relevant prognostic factors in these patients were then analyzed. Moreover, the association of FOXM1 expression and chemosensitivity to docetaxel in gastric cancer cells was further explored. Results Our study demonstrated that the level of FOXM1 expression was significantly higher in gastric cancer than in para-cancer tissues (P < 0.001) and normal gastric cell lines (P = 0.026). No significant association was found between FOXM1 expression and any clinical pathological features (P > 0.1). FOXM1 amplification was identified as an independent prognostic factor in gastric cancer (P = 0.001), and its affection is more significant in patients with tumor size larger than 5 cm (P = 0.004), pT3-4 (P = 0.003) or pIII-IV (P = 0.001). Additionally, shown to mediate docetaxel resistance in gastric cancers by our research, FOXM1 was revealed to alter microtubule dynamics in response to the treatment of docetaxel, and the drug resistance could be reversed with FOXM1 inhibitor thiostrepton treatment. Conclusions FOXM1 can be a useful marker for predicting patients’ prognosis and monitoring docetaxel response, and might be a new therapeutic target in docetaxel resistant gastric cancer. PMID:24004449

  1. Nuclear survivin expression is a positive prognostic factor in taxane-platinum-treated ovarian cancer patients

    PubMed Central

    2011-01-01

    Background Survivin is an inhibitor of apoptosis and a regulator of mitotic progression. TP53 protein is a negative transcriptional regulator of survivin. The aim of our study was to evaluate the clinical significance of survivin expression in advanced stages ovarian cancer with respect to the TP53 status. Methods Survivin and TP53 expression was evaluated immunohistochemically in 435 archival samples of ovarian carcinomas (244 patients were treated with platinum/cyclophosphamide-PC/PAC; 191-with taxane-platinum (TP) agents). Univariate and multivariate statistical analyses were performed in patients groups divided according to the administered chemotherapeutic regimen, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively). Results Nuclear and cytoplasmic survivin expression was observed in 92% and 74% of the carcinomas, respectively. In patients treated with TP, high nuclear survivin expression decreased the risk of disease recurrence and death, and increased the probability of high platinum sensitivity (p < 0.01), but only in the TP53(+) group, and not in the TP53(-) group. Conclusions It appears that TP53 status determines the clinical importance of nuclear survivin expression in taxane-platinum treated ovarian cancer patients. PMID:22075440

  2. Tumor cell expression of MMP3 as a prognostic factor for poor survival in pancreatic, pulmonary, and mammary carcinoma

    PubMed Central

    Mehner, Christine; Miller, Erin; Nassar, Aziza; Bamlet, William R.; Radisky, Evette S.; Radisky, Derek C.

    2015-01-01

    Breast, lung, and pancreatic cancers collectively represent one third of all diagnosed tumors and are responsible for almost 40% of overall cancer mortality. Despite improvements in current treatments, efforts to develop more specific therapeutic options are warranted. Here we identify matrix metalloproteinase 3 (MMP3) as a potential target within all three of these tumor types. MMP3 has previously been shown to induce expression of Rac1b, a tumorigenic splice isoform of Rac1. In this study we find that MMP3 and Rac1b proteins are both strongly expressed by the tumor cells of all three tumor types and that expression of MMP3 protein is prognostic of poor survival in pancreatic cancer patients. We also find that MMP3 gene expression can serve as a prognostic marker for patient survival in breast and lung cancer. These results suggest an oncogenic MMP3-Rac1b signaling axis as a driver of tumor progression in three common poor prognosis tumor types, further suggesting that new therapies to target these pathways could have substantial therapeutic benefit. PMID:26807201

  3. [Prognostic factors of early breast cancer].

    PubMed

    Almagro, Elena; González, Cynthia S; Espinosa, Enrique

    2016-02-19

    Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies. PMID:25726309

  4. Prognostic factors in lupus nephritis.

    PubMed

    Mok, C C

    2005-01-01

    Systemic lupus erythematosus (SLE) is a heterogeneous disorder and its renal manifestations are protean. The course and prognosis of lupus nephritis is dependent on a large number of demographic, histopathological, serological, racial, socioeconomic and time dependent factors. Moreover, the initial and maintenance therapeutic regimens may also influence the long term renal outcome. This article reviews the important prognostic factors that have been reported in literature. The management strategy of lupus nephritis should be individualized and based on a composite of these parameters. PMID:15732286

  5. Cyclin D1 expression in colorectal cancer is a favorable prognostic factor in men but not in women in a prospective, population-based cohort study

    PubMed Central

    2011-01-01

    Background Although colorectal cancer (CRC) is generally not considered to be a hormone-dependent malignancy, several sex-related differences in incidence, molecular characteristics and survival have been reported. Epidemiological studies have consistently shown that increased exposure to female sex hormones is associated with a lower risk of CRC in women, and cyclin D1, an important downstream effector in estrogen-mediated signaling, is commonly activated in CRC. In this study, we analyzed the prognostic significance of cyclin D1 expression in CRC, with particular reference to sex-related differences, in tumors from a large, prospective, population-based cohort. Methods Using tissue microarrays and immunohistochemistry, the fraction and intensity of cyclin D1 expression was evaluated in 527 incident CRC cases from the Malmö Diet and Cancer Study. The χ2 and Spearman's rho (ρ) tests were used for comparison of cyclin D1 expression and relevant clinicopathological characteristics. Kaplan-Meier analysis and Cox proportional hazards modeling were used to assess the effect of cyclin D1 expression on cancer-specific survival (CSS) in univariate and multivariate analysis, adjusted for established prognostic factors. Results Cyclin D1 intensity was significantly lower in male compared with female CRC (P = 0.018). In the full cohort, cyclin D1 expression was associated with a significantly prolonged CSS (hazard ratio (HR) = 0.69; 95% CI 0.49 to 0.96, P = 0.026) but subgroup analysis according to gender revealed a strongly accentuated prognostic effect of cyclin D1 in male CRC (HR = 0.48; 95% CI 0.31 to 0.74, P < 0.001), which was in contrast to female CRC, where cyclin D1 was not prognostic (HR = 1.05; 95% CI 0.62 to 1.78, P = 0.864) (Pinteraction = 0.024). The prognostic value of cyclin D1 was not retained in multivariate analysis, either in the full cohort or in male CRC. Conclusions Cyclin D1 expression is strongly associated with prolonged survival in male CRC

  6. UBE2D3 is a positive prognostic factor and is negatively correlated with hTERT expression in esophageal cancer

    PubMed Central

    GUAN, GE GE; WANG, WEN BO; LEI, BING XIN; WANG, QIAO LI; WU, LIN; FU, ZHEN MING; ZHOU, FU XIANG; ZHOU, YUN FENG

    2015-01-01

    Human telomerase reverse transcriptase (hTERT) is a critical factor in unlimited cell proliferation and immortalization, with numerous studies demonstrating that high expression of hTERT is a poor prognostic factor in various types of cancer. Ubiquitin-conjugating enzyme E2D 3 (UBE2D3) is a member of the E2 family, and participates in the ubiquitin proteasome pathway to regulate basic cellular activities, such as cell cycle control, the DNA damage response, apoptosis, and tumorigenesis. Our previous study initially determined that downregulation of UBE2D3 expression increases hTERT expression and cell proliferation, however, the association between the expression of these two proteins and their functions in cancer tissues remains unknown. Therefore, the protein expression levels of hTERT and UBE2D3 were evaluated in 150 esophageal cancer and 30 adjacent healthy tissue samples by performing immunohistochemical analysis. Concurrently, the clinicopathological data of the enrolled patients were obtained to allow correlation analysis. It was identified that the expression of hTERT in the esophageal cancer tissues was significantly higher compared with that of the adjacent tissues (P=0.015), however, the expression of UBE2D3 was significantly lower in esophageal cancer tissues than the adjacent tissues (P=0.001). Additionally, the study demonstrated that hTERT was significantly upregulated in poorly-differentiated, advanced tumor-node-metastasis (TNM) stage cancer tissues (P<0.05 for all), however, UBE2D3 expression was downregulated in poorly-differentiated, lymph node invaded cancer tissues and recurrent cases. It was also identified that traditional factors, including tumor location, T stage, lymph node status, TNM stage, and molecular factors of hTERT and UBE2D3, were significantly associated with overall survival time (P<0.05 for all). Furthermore, UBE2D3, lymph node status and tumor location were independent prognostic factors for esophageal cancer in multivariate

  7. Prognostic factors in histiocytosis X.

    PubMed

    Lahey, M E

    1981-01-01

    It is now clear that the prognosis in children with histiocytosis X has improved considerable over the past few years. To be sure, patients with solitary lesions have an excellent prognosis. Whereas the outlook for patients with significant visceral involvement is not as good as those with bone lesions only, the outlook is by no means hopeless, as was once thought. A number of prognostic factors have been reviewed here. The most significant of these factors at the present time would appear to be age of onset of the disease, extent of involvement, the rapidity of progression of the disease, and, in particular, the presence or absence of dysfunction of such crucial organ systems as liver, lung, and hemopoietic system. Further studies of the significance of histologic features and immunologic findings are clearly needed to further our understanding of this disorder. PMID:6972178

  8. Ubiquitin-specific protease 7 expression is a prognostic factor in epithelial ovarian cancer and correlates with lymph node metastasis

    PubMed Central

    Ma, Ming; Yu, Nina

    2016-01-01

    Objective Ubiquitin-specific protease 7 (USP7) is a common target of herpesviruses and is important in the DNA damage response, which is also upregulated in several cancers, including prostate, colon, liver, and lung cancers. However, less is known about its expression in ovarian cancer tissues. The role of USP7 in epithelial ovarian cancer (EOC) has not yet been investigated. Materials and methods We recruited 141 patients from Linyi People’s Hospital between June 1999 and June 2013, all pathologically diagnosed with primary EOC. Their clinical data were collected, and the expression of USP7 in the tumor tissues was determined using immunohistochemistry. The correlations between USP7 expression and the clinicopathological variables of patients with EOC were assessed using Spearman’s rank correlation test. Kaplan–Meier analysis and Cox regression analysis were used to identify the prognosis value of USP7. The function of USP7 in the EOC cells was also detected in vitro. Results Among the 141 cases, USP7 expression was high in 59 EOC samples (41.8%), and was significantly correlated with lymphatic invasion; USP7 can act as independent prognostic indicator for the overall survival (OS) of EOC, and its high expression was associated with poor OS rate. The RNA inteference and overexpression assays indicated that USP7 can positively regulate the ovarian cell vitality and invasion process. Conclusion Patients with EOC expressing high level of USP7 have worse OS compared with those with low USP7 expression. USP7 may be involved in the proliferation and invasion of EOC cells, and USP7 expression can serve as an independent predictor of EOC. PMID:27051296

  9. Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression.

    PubMed Central

    Fontanini, G.; Vignati, S.; Lucchi, M.; Mussi, A.; Calcinai, A.; Boldrini, L.; Chiné, S.; Silvestri, V.; Angeletti, C. A.; Basolo, F.; Bevilacqua, G.

    1997-01-01

    Following up-regulation of an angiogenesis inhibitor by the wild-type p53 protein proven recently, we have analysed on the one hand the prognostic impact of microvessel count (MC) and p53 protein overexpression in non-small-cell lung carcinoma (NSCLC) progression and, on the other hand, the inter-relation between the microvascular pattern and the p53 protein expression. Moreover, we assessed the expression of vascular endothelial growth factor (VEGF), one of the pivotal mediators of tumour angiogenesis, in order to investigate its relation to p53 protein expression and MC. Tumours from 73 patients resected for NSCLC between March 1991 and April 1992 (median follow-up 47 months, range 32-51 months) were analysed using an immunohistochemical method. In univariate analysis, MC and p53 accumulation were shown to affect metastatic nodal involvement, recurrence and death significantly. Multiple logistic regression analysis showed an important prognostic influence of MC and nodal status on overall (P = 0.0009; P = 0.01) and disease-free survival (P = 0.0001; P = 0.03). Interestingly, a strong statistical association was observed between p53 nuclear accumulation and MC (P = 0.0003). The same inter-relationship was found in non-squamous histotype (P = 0.002). When we analysed the concomitant influence of MC and p53 expression on overall survival, we were able to confirm a real predominant role of MC in comparison with p53. With regard to VEGF expression, p53-negative and lowly vascularized tumours showed a mean VEGF expression significantly lower than p53-positive and highly vascularized cancers (P = 0.02). These results underline the prognostic impact of MC and p53 protein accumulation in NSCLC and their reciprocal inter-relationship, supporting the hypothesis of a wild-type p53 regulation on the angiogenetic process through a VEGF up-regulation. Images Figure 1 Figure 3 Figure 8 PMID:9155049

  10. CEA Level, Radical Surgery, CD56 and CgA Expression Are Prognostic Factors for Patients With Locoregional Gastrin-Independent GNET

    PubMed Central

    Li, Yuan; Bi, Xinyu; Zhao, Jianjun; Huang, Zhen; Zhou, Jianguo; Li, Zhiyu; Zhang, Yefan; Li, Muxing; Chen, Xiao; Hu, Xuhui; Chi, Yihebali; Zhao, Dongbing; Zhao, Hong; Cai, Jianqiang

    2016-01-01

    Abstract Gastrin-independent gastric neuroendocrine tumors (GNETs) are highly malignant. Radical resections and lymphadenectomy are considered to be the only possible curative treatment for these tumors. However, the prognosis of gastrin-independent GNETs is not well defined. In this study, we identified prognostic factors of locoregional gastrin-independent GNETs. All patients diagnosed with locoregional gastrin-independent GNETs between 2000 and 2014 were included in this retrospective study. Clinical characteristics, blood tests, pathological characteristics, treatments, and follow-up data of the patients were collected and analyzed. Of the 66 patients diagnosed with locoregional gastrin-independent GNETs, 57 (86.4%) received radical resections, 7 (10.6%) with palliative resection, 1 (1.5%) with gastrojejunostomy, and 1 (1.5%) with exploration surgeries. The median survival time for these patients was 19.0 months (interquartile range, 11.0–38.0). The 1-, 3-, and 5-year survival rates were 72%, 34%, and 28%, respectively. Multivariate analysis indicated that carcinoembryonic antigen (CEA) level (P = 0.04), radical resection (P = 0.04), and positive Cluster of Differentiation 56 (CD56) expression (P = 0.016) were significant prognostic factors on overall survival rate. Further univariate and multivariate analysis of 57 patients who received radical resections found that CgA expression (P = 0.35) and CEA level (P = 0.33) are independent prognostic factors. Gastrin-independent GNETs had poor prognosis. Serum CEA level, radical surgery, CD56 and CgA expression are markers to evaluate the survival of patients with locoregional gastrin-independent GNETs. PMID:27149478

  11. Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma.

    PubMed

    Togami, Shinichi; Sasajima, Yuko; Oi, Takateru; Ishikawa, Mitsuya; Onda, Takashi; Ikeda, Shun-Ichi; Kato, Tomoyasu; Tsuda, Hitoshi; Kasamatsu, Takahiro

    2012-05-01

    Uterine papillary serous carcinoma (UPSC) is a rare and aggressive variant of endometrial carcinoma. Little is known about the pathological and biological features of this tumor. Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) expression have an important role in tumor behavior and clinical outcome, but their relevance in UPSC is not clear. In the present study, the immunohistochemical expression of HER2 and HR was assessed in 27 patients with Stage I disease, 13 with Stage II disease, 25 with Stage III disease, and 6 with Stage IV disease. Correlations between HER2 and HR expression and the clinicopathological parameters of UPSC were evaluated using Cox's univariate and multivariate analyses. For all patients, the 5-year recurrence-free survival (RFS) and overall survival (OS) rates were 51% and 66%, respectively; in patients with Stage I, II, III and IV disease, the RFS and OS were 67%/81%, 59%/77%, 43%/54% and 0%/0%, respectively. Of all 71 patients, 14% (10/71) were positive for HER2 and 52% (37/71) were positive for HR. Overexpression of HER2 was correlated with lower OS (P = 0.01), whereas HR overexpression was correlated with higher OS (P = 0.008). In multivariate models, HER2, HR, and histologic subtype were identified as independent prognostic indicators for RFS (P = 0.022, P = 0.018, and P = 0.01, respectively), but HR was the only independent factor associated with OS (P = 0.044). Thus, HER2 and HR are prognostic variables in UPSC, with HR an independent prognostic factor for OS. PMID:22329832

  12. ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas.

    PubMed

    Fan, Xing; Wang, Yongheng; Zhang, Chuanbao; Liu, Li; Yang, Sen; Wang, Yinyan; Liu, Xing; Qian, Zenghui; Fang, Shengyu; Qiao, Hui; Jiang, Tao

    2016-01-01

    The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients. PMID:27571068

  13. Prognostic factors in canine mammary cancer.

    PubMed

    Misdorp, W; Hart, A A

    1976-04-01

    From a follow-up study of dogs surgically treated for mammary cancer, ten characteristics were analyzed statistically with special reference to their association with prognosis (expressed as survival for 2 years). The interrelations among five of the characteristics were also tested. The histologic type (descending range in malignancy: sarcomas greater than simple carcinomas greater than complex carcinomas), mode of growth (highly infiltrating greater than moderately infiltrating greater than expansive), clinical stage of complex carcinomas (large tumors and/or tumors involving the skin or underlying tissue greater than small, well-defined tumors), and size (greater than 15 cm greater than 11-15 cm greater than 5-10 cm greater than 0-5 cm) were of definite prognostic importance. The histologic grade was of possible prognostic importance. Localization, type of surgical therapy (mastectomy, block-dissection), growth in lymph vessels, involvement of regional lymph nodes, and duration of symptoms before treatment were not important to prognosis. A comparison between the factors associated with the prognosis of canine and human mammary cancer showed many similarities. However, the involvement of regional lymph nodes, important in women, was not so in bitches. PMID:1255797

  14. PARP-1 expression in CD34+ leukemic cells in childhood acute lymphoblastic leukemia: relation to response to initial therapy and other prognostic factors.

    PubMed

    Kruk, Agnieszka; Ociepa, Tomasz; Urasiński, Tomasz; Grabarek, Jerzy; Urasińska, Elzbieta

    2015-09-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that impacts DNA repair and apoptosis. Both experimental and ongoing clinical studies indicate that PARP-1 inhibitors are potent and promising anticancer agents. However, the outcome of treatment with PARP-1 inhibitors depends on the expression of PARP-1 protein in the tumor cells. This study aimed to assess PARP-1 expression in peripheral blood CD34+ leukemic cells before and after 12 hours of prednisone administration as well as the relation between PARP-1 expression and early treatment response to initial therapy and other prognostic factors (immunophenotype, age, initial peripheral blood white blood count [WBC], and risk factor group). The study comprised 43 children with de novo ALL. Cytospins of peripheral blood were stained with mouse anti-CD34-FITC and anti-PARP-1 antibody followed by goat anti-mouse APC-conjugated antibody. DNA was counterstained with PI (propidium iodide). Cellular fluorescence was measured by a laser scanning cytometer. Statistically significant differences in baseline PARP-1 expression with respect to early treatment response (good vs. poor), ALL immunophenotype (ALL B vs. ALL T), age (children < 1 years and > 6 years vs. children 1-6 years), initial WBC (< 20 000/µl vs. ≥ 20 000/µl), and risk factor group (SR vs. IR vs. HR) were not found. PARP-1 expression was increased 12 hours after treatment in poor early treatment responders, whereas it remained statistically unchanged with respect to ALL immunophenotype, age, initial WBC, risk factor group and early treatment response. The overexpression of PARP-1 in poor early treatment responders suggests that it may contribute to treatment failure in this group of children with ALL. Our observation - if confirmed by other studies - may form the rationale for administration of PARP inhibitors in selected subsets of ALL children. PMID:26619102

  15. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

    PubMed Central

    Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

  16. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

    PubMed

    Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

  17. A serum microRNA signature as a prognostic factor for patients with advanced NSCLC and its association with tissue microRNA expression profiles

    PubMed Central

    GUO, JING; MENG, RUI; YIN, ZHONGYUAN; LI, PENGCHENG; ZHOU, RUI; ZHANG, SHENG; DONG, XIAORONG; LIU, LI; WU, GANG

    2016-01-01

    The aim of the present study was to detect microRNA (miRNA) signatures in advanced non-small cell lung cancer (NSCLC), and to study the association between miRNA expression levels in serum and tissue. A cohort of patients who had previously been diagnosed with advanced NSCLC was enrolled in the present study. miRNAs associated with prognosis, which had previously been detected in early stage NSCLC samples, were measured in the serum of the patient groups using a cross-validation method. In addition, serum miRNAs associated with progression-free survival (PFS) were detected in paired fresh tissue samples, in order to analyze the correlation between serum and tissue expression levels. A risk-score analysis was used to develop a four-miRNA signature to predict PFS. miR-1, miR-30d, miR-221 and miR-486 were identified as having a significant correlation with PFS in advanced NSCLC. miR-221 and miR-486 exhibited significant positive correlations between serum and tissue expression. Furthermore, overexpression of miR-221 and reduced expression of miR-486 increased cell proliferation, migration and invasion in vitro. In conclusion, the miRNA signature identified in the present study may be considered an independent prognostic factor of PFS in advanced NSCLC. In addition, the expression levels of miR-221 and miR-486 were significantly correlated between serum and tissue. miR-221 was identified as an oncogenic risk factor, whereas miR-486 exerted protective effects against cancer cell proliferation, migration and invasion. PMID:27081922

  18. Prognostic Factors in Childhood Leukemia (ALL or AML)

    MedlinePlus

    ... for childhood leukemias Prognostic factors in childhood leukemia (ALL or AML) Certain factors that can affect a ... myelogenous leukemia (AML). Prognostic factors for children with ALL Children with ALL are often divided into risk ...

  19. High Id1 expression, a generally negative prognostic factor, paradoxically predicts a favorable prognosis for adjuvant paclitaxel plus cisplatin therapy in surgically treated lung cancer patients

    PubMed Central

    Cheng, Yu-Jen; Lee, Yi-Chen; Chiu, Wen-Chin; Tsai, Jen-Wei; Su, Yu-Han; Hung, Amos C.; Chang, Po-Chih; Huang, Chih-Jen; Chai, Chee-Yin; Yuan, Shyng-Shiou F.

    2014-01-01

    Adjuvant chemotherapy is commonly given to surgically treated non-small-cell lung cancer (NSCLC) patients. However, the prerequisite for chemotherapy needs to be scrutinized in order to maximize the benefits to patients. In this study, we observed that NSCLC cells with high Id1 protein expression were vulnerable to the treatment of paclitaxel and cisplatin. In addition, paclitaxel and cisplatin caused Id1 protein degradation through ubiquitination. In the nude mice xenograft model, the tumor growth was reduced to a large degree in the Id1-overexpressing group upon treatment with paclitaxel and cisplatin. Furthermore, immunohistochemical staining for Id1 followed by Kaplan-Meier survival analysis showed that surgically treated NSCLC patients with high Id1 expression in primary tumor tissues had better disease-free and overall survivals after adjuvant paclitaxel and cisplatin chemotherapy. In summary, our current data suggest that Id1, a generally negative prognostic factor, predicts a favorable prognosis in the case of surgically treated NSCLC patients receiving the definitive adjuvant chemotherapy. The distinct role of Id1 reported in this study may arise from the phenomenon of Id1 dependence of NSCLC cells for survival, which renders the cancer cells additionally susceptive to the adjuvant chemotherapy with paclitaxel and cisplatin. PMID:25344919

  20. Decreased Expression of CXCR4 Chemokine Receptor in Bone Marrow after Chemotherapy in Patients with Non-Hodgkin Lymphomas Is a Good Prognostic Factor

    PubMed Central

    Mazur, Grzegorz; Butrym, Aleksandra; Kryczek, Ilona; Dlubek, Dorota; Jaskula, Emilia; Lange, Andrzej; Kuliczkowski, Kazimierz; Jelen, Michal

    2014-01-01

    Background CXCR4 chemokine receptor is constitutively expressed on normal and malignant B lymphocytes derived from patients with B-cell lymphoproliferative disorders and has a significant role in cell migration to lymph nodes and bone marrow. Non-Hodgkin's lymphomas (NHL) constitute a heterogeneous group of lymphoproliferative diseases, which can localize not only to lymph nodes, but also can migrate to peripheral blood and metastase to other organs, including bone marrow. Aim The purpose of this study was to determine CXCR4 gene expression in peripheral blood and bone marrow of NHL patients before and after treatment. Methods Samples of lymphoma lymph nodes, peripheral blood and bone marrow aspirates of patients with B-cell NHL were taken at diagnosis and after chemotherapy. Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Expression was estimated from 0 AU (no amplificate signal) to 3 AU (maximal amplificate signal). Results No significant difference in the level of CXCR4 expression was found in reactive lymph nodes compared to lymphoma samples We observed high level of CXCR4 expression in most patients before treatment: in bone marrow: 3 AU-10 pts, 2 AU–8 pts, 1 AU–2 pts. In peripheral blood: 3 AU–14 pts, 2 AU–4 pts, 1 AU–1 pts, 0 AU–1 pts. After chemotherapy, significant decrease in CXCR4 expression was observed. Bone marrow: 3 AU–5 pts, 2 AU–7 pts, 1 AU–5 pts, 0 AU–3 pts (p = 0.03). Peripheral blood: 3 AU–2 pts, 2 AU–6 pts, 1 AU–10 pts, 0 AU–2 pts (p = 0.0002). There was a good response to treatment in patients with significant decrease of CXCR4 expression in the bone marrow after treatment with 10-fold lower risk of death (p = 0.03). Conclusions Decrease in CXCR4 expression in the bone marrow of NHL patients after chemotherapy may be a good prognostic factor. PMID:24859274

  1. The Biochemical Prognostic Factors of Subclinical Hypothyroidism

    PubMed Central

    Lee, Myung Won; Shin, Dong Yeob; Kim, Kwang Joon; Hwang, Sena

    2014-01-01

    Background Patients with subclinical hypothyroidism (SHT) are common in clinical practice. However, the clinical significance of SHT, including prognosis, has not been established. Further clarifying SHT will be critical in devising a management plan and treatment guidelines for SHT patients. Thus, the aim of this study was to investigate the prognostic factors of SHT. Methods We reviewed the medical records of Korean patients who visited the endocrinology outpatient clinic of Severance Hospital from January 2008 to September 2012. Newly-diagnosed patients with SHT were selected and reviewed retrospectively. We compared two groups: the SHT maintenance group and the spontaneous improvement group. Results The SHT maintenance group and the spontaneous improvement group had initial thyroid-stimulating hormone (TSH) levels that were significantly different (P=0.035). In subanalysis for subjects with TSH levels between 5 to 10 µIU/mL, the spontaneous improvement group showed significantly lower antithyroid peroxidase antibody (anti-TPO-Ab) titer than the SHT maintenance group (P=0.039). Regarding lipid profiles, only triglyceride level, unlike total cholesterol and low density lipoprotein cholesterol, was related to TSH level, which is correlated with the severity of SHT. Diffuse thyroiditis on ultrasonography only contributed to the severity of SHT, not to the prognosis. High sensitivity C-reactive protein and urine iodine excretion, generally regarded as possible prognostic factors, did not show any significant relation with the prognosis and severity of SHT. Conclusion Only initial TSH level was a definite prognostic factor of SHT. TPO-Ab titer was also a helpful prognostic factor for SHT in cases with mildly elevated TSH. Other than TSH and TPO-Ab, we were unable to validate biochemical prognostic factors in this retrospective study for Korean SHT patients. PMID:25031888

  2. Dicer Gene Expression as a Prognostic Factor in Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia in Fars Province

    PubMed Central

    Farzaneh, Mohamad Reza; Shahryari, Jahanbanoo; Safaei, Akbar; Valibeigi, Behnaz; Davani, Shahrbanou Karimi; Tabibi, Narjes

    2016-01-01

    Alterations in the expression of microRNAs (miRNAs) have been proposed to play a role in the pathogenesis of acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Dicer is one of the main regulators of miRNA biogenesis, and deregulation of its expression has been indicated as a possible cause of miRNA alterations observed in various cancers. Our aim was to analyze the expression of the Dicer protein and its relationship with ALL and CLL. This cross-sectional study was performed from 2010 to 2012 in Shahid Faghihi Hospital, Shiraz, Iran. In this study, 30 patients with CLL, 21 patients with ALL, 10 child healthy donors, and 19 adult healthy donors were recruited. The patients’ samples were checked via flow cytometry, immunohistochemistry, and immunocytochemistry. The controls’ samples were also examined in the hematology ward. Total RNA was extracted from the bone marrow and peripheral blood samples of the patients and controls. Then, reverse-transcription polymerase chain reaction was used to estimate the level of Dicer miRNA. The outcomes of the expression analysis of Dicer revealed statistically significant differences between the ALL patients/child healthy controls (mean±SD, 0.19±0.28 vs. 0.73±0.12; P<0.001) and the CLL patients/adult healthy controls (mean±SD, 0.24±0.25 vs. 0.41±0.28; P=0.033). This is the first piece of evidence showing that the expression of the Dicer gene greatly decreased in the patients with ALL in comparison to the child controls. The expression of the Dicer gene was also downregulated in the patients with CLL compared to the adult controls. Given the above findings, the expression of Dicer may play an important role in the progression and prognosis of these diseases. PMID:27217607

  3. HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.

    PubMed

    Ge, Xiao-Song; Ma, Hua-Juan; Zheng, Xiao-Hui; Ruan, Hong-Lian; Liao, Xiao-Yu; Xue, Wen-Qiong; Chen, Yuan-Bin; Zhang, Ying; Jia, Wei-Hua

    2013-12-01

    Long non-coding RNAs (LncRNAs) have been recently found to be pervasively transcribed in the genome and critical regulators of the epigenome. HOTAIR, as a well-known LncRNA, has been found to play important roles in several tumors. Herein, the clinical application value and biological functions of HOTAIR were focused and explored in esophageal squamous cell carcinoma (ESCC). It was found that there was a great upregulation of HOTAIR in ESCC compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro. Then some specific molecules with great significance were investigated after HOTAIR overexpression using microarray and quantitative real time-polymerase chain reaction (qPCR). WIF-1 playing an important role in Wnt/β-catenin signaling pathway was selected and further tested by immunehistochemistry. Generally, inverse correlation between HOTAIR and WIF-1 expression was demonstrated both in ESCC cells and tissues. Mechanistically, HOTAIR directly decreased WIF-1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the Wnt/β-catenin signaling pathway. This newly identified HOTAIR/WIF-1 axis clarified the molecular mechanism of ESCC cell metastasis and represented a novel therapeutic target in patients with ESCC. PMID:24118380

  4. A prognostic gene expression signature in infratentorial ependymoma

    PubMed Central

    Wani, Khalida; Armstrong, Terri; Vera-Bolanos, Elizabeth; Raghunathan, Aditya; Ellison, David; Gilbertson, Richard; Vaillant, Brian; Goldman, Stewart; Packer, Roger J.; Fouladi, Maryam; Pollack, Ian; Mikkelsen, Tom; Prados, Michael; Omuro, Antonio; Soffietti, Riccardo; Ledoux, Alicia; Wilson, Charmaine; Long, Lihong; Gilbert, Mark; Aldape, Ken

    2013-01-01

    Patients with ependymoma exhibit a wide range of clinical outcomes that is currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggests that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse-transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically-identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors. PMID:22322993

  5. Clinicopathological Differences and Prognostic Value of Hypoxia-Inducible Factor-2α Expression for Gastric Cancer: Evidence From Meta-Analysis.

    PubMed

    Zheng, Fangchao; Du, Feng; Zhao, Jiuda

    2016-02-01

    Published literatures have reported the relationship between hypoxic-inducible factor-2α (HIF-2α) expression and clinicopathological features in gastric cancer (GC), but the evaluated conclusions remain controversial. A meta-analysis was carried to examine the clinicopathological features and prognostic values of HIF-2α in patients with GC. Systematic detailed searches were performed to Pub Med, Cochrane Library, and EBSCO until to August 2015. Six studies (508 specimens) were included in this meta-analysis. HIF-2α-positive expression indicates an unfavorable prognosis value and advanced clinicopathological differences for the available patient dates with GC. Further multivariate meta-analysis revealed that HIF-2α-positive expression in gastric cancer associated with deeper tumor infiltration (OR = 3.08; 95%CI: 1.18-8.04), higher rates of lymphatic metastasis (OR = 3.26; 95%CI: 1.10-9.63), higher TNM stage (III+IV) (OR = 2.61; 95%CI: 1.40-4.84), and much lower 5-year overall survival (OR = 2.08; 95%CI: 1.21-3.58). Nevertheless, there is no association between HIF-2α-positive expression and worse tumor differentiation (OR = 2.03; 95%CI: 0.73-5.64). In addition, by this subgroup analysis, HIF-2α-positive expression associated with deeper tumor infiltration (OR = 3.81; 95%CI: 1.03-14.08), higher lymphatic metastasis (OR = 4.71; 95%CI: 1.08-20.50), higher TNM stage (OR = 3.21; 95%CI: 1.57-6.57), worse tumor differentiation (OR = 3.08; 95%CI: 1.51-6.31), and lower 5-year overall survival (OR = 2.34; 95%CI: 1.15-4.79). Our results indicate that HIF-2α overexpression can potently predict the poor prognosis and may be a potential therapeutic target for gastric carcinoma, according to the limited evidence. Meanwhile, further studies are needed to elucidate the accuracy of these results. PMID:26886654

  6. Prognostic factors in neuroendocrine cervical carcinoma

    PubMed Central

    Lee, Da Yong; Chong, Chul; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang; Park, Sang Yoon

    2016-01-01

    Objective To evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC). Methods The records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses. Results Of the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size ≥2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence. Conclusion Tumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed. PMID:27004202

  7. Sun exposure and melanoma prognostic factors

    PubMed Central

    GANDINI, SARA; MONTELLA, MAURIZIO; AYALA, FABRIZIO; BENEDETTO, LUCIA; ROSSI, CARLO RICCARDO; VECCHIATO, ANTONELLA; CORRADIN, MARIA TERESA; DE GIORGI, VINCENZO; QUEIROLO, PAOLA; ZANNETTI, GUIDO; GIUDICE, GIUSEPPE; BORRONI, GIOVANNI; FORCIGNANÒ, ROSACHIARA; PERIS, KETTY; TOSTI, GIULIO; TESTORI, ALESSANDRO; TREVISAN, GIUSTO; SPAGNOLO, FRANCESCO; ASCIERTO, PAOLO A.

    2016-01-01

    Previous studies have reported an association between sun exposure and the increased survival of patients with cutaneous melanoma (CM). The present study analyzed the association between ultraviolet (UV) light exposure and various prognostic factors in the Italian Clinical National Melanoma Registry. Clinical and sociodemographic features were collected, as well as information concerning sunbed exposure and holidays with sun exposure. Analyses were performed to investigate the association between exposure to UV and melanoma prognostic factors. Between December 2010 and December 2013, information was obtained on 2,738 melanoma patients from 38 geographically representative Italian sites. A total of 49% of the patients were >55 years old, 51% were men, 50% lived in the north of Italy and 57% possessed a high level of education (at least high school). A total of 8 patients had a family history of melanoma and 56% had a fair phenotype (Fitzpatrick skin type I or II). Of the total patients, 29% had been diagnosed with melanoma by a dermatologist; 29% of patients presented with a very thick melanoma (Breslow thickness, >2 mm) and 25% with an ulcerated melanoma. In total, 1% of patients had distant metastases and 13% exhibited lymph node involvement. Holidays with sun exposure 5 years prior to CM diagnosis were significantly associated with positive prognostic factors, including lower Breslow thickness (P<0.001) and absence of ulceration (P=0.009), following multiple adjustments for factors such as sociodemographic status, speciality of doctor performing the diagnosis and season of diagnosis. Sunbed exposure and sun exposure during peak hours of sunlight were not significantly associated with Breslow thickness and ulceration. Holidays with sun exposure were associated with favorable CM prognostic factors, whereas no association was identified between sunbed use and sun exposure during peak hours of sunlight with favorable CM prognostic factors. However, the results of the

  8. High expression of peroxiredoxin 4 affects the survival time of colorectal cancer patients, but is not an independent unfavorable prognostic factor

    PubMed Central

    YI, NAN; XIAO, MING BING; NI, WEN KAI; JIANG, FENG; LU, CUI HUA; NI, RUN-ZHOU

    2014-01-01

    Peroxiredoxin 4 (Prx4) has a number of important biological functions, such as efficient antioxidant capacity and promotion of cell proliferation and differentiation. The purpose of this study was to investigate the expression and significance of Prx4 in human colorectal cancer (CRC). Quantitative polymerase chain reaction (qPCR) was performed to detect Prx4 in 8 freshly frozen specimens of CRC and their adjacent normal tissues. In addition, immunohistochemical analysis was performed to detect Prx4 in 59 specimens of CRC and 26 of adjacent normal tissues. The immunohistochemical and qPCR results demonstrated that the expressions of the Prx4 gene and protein were higher in CRC compared to those in the adjacent normal tissues. The expression intensity of the Prx4 protein was correlated with depth of invasion (P=0.001), lymph node metastasis (P=0.006) and Dukes’ classification (P=0.004) in CRC. The Kaplan-Meier survival curves revealed that high Prx4 expression was correlated with short survival time. However, the Cox proportional hazards regression analysis did not identify Prx4 as an independent prognostic marker for CRC (P>0.05). These results suggested that Prx4 may be associated with carcinogenesis and the development of CRC and it may be a prognostic marker for postoperative CRC patients. PMID:25054044

  9. Prognostic Factors After Extraneural Metastasis of Medulloblastoma

    SciTech Connect

    Mazloom, Ali; Zangeneh, Azy H.; Paulino, Arnold C.

    2010-09-01

    Purpose: To review the existing literature regarding the characteristics, prognostic factors, treatment, and survival of patients with medulloblastoma, who develop extraneural metastasis (ENM). Methods and Materials: A PubMed search of English language articles from 1961 to 2007 was performed, yielding 47 articles reporting on 119 patients. Factors analyzed included age, time interval to development of ENM, ENM location, central nervous system (CNS) involvement, treatment, and outcome. Results: Sites of ENM included bone in 84% of patients, bone marrow in 27% of patients, lymph nodes in 15% of patients, lung in 6% of patients, and liver in 6% of patients. Median survival was 8 months after diagnosis of ENM. The 1-, 2-, and 5-year overall survival (OS) rates after diagnosis of ENM were 41.9%, 31.0%, and 26.0%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates after diagnosis of ENM were 34.5%, 23.2%, and 13.4%, respectively. For patients without CNS involvement at the time of ENM diagnosis, the 1-, 2-, and 5-year OS rates for those treated with and without radiotherapy (RT) were 82.4%, 64.8%, and 64.8% vs. 51.0%, 36.6%, and 30.5%, respectively (p = 0.03, log-rank test). RT did not significantly improve OS or PFS rates for those with CNS involvement. Concurrent CNS involvement, ENM in the lung or liver, a time interval of <18 months to development of ENM, and a patient age of <16 years at ENM diagnosis were found to be negative prognostic factors for both OS and PFS. Conclusions: Several prognostic factors were identified for patients with ENM from medulloblastoma. Patients without concurrent CNS involvement, who received RT after ENM diagnosis had an OS and PFS benefit compared to those who did not receive RT.

  10. Prognostic impact of KI67, p53, human epithelial growth factor receptor 2, topoisomerase IIalpha, epidermal growth factor receptor, and nm23 expression of ovarian carcinomas and disseminated tumor cells in the bone marrow.

    PubMed

    Schindlbeck, C; Hantschmann, P; Zerzer, M; Jahns, B; Rjosk, D; Janni, W; Rack, B; Sommer, H; Friese, K

    2007-01-01

    Examination of tumor biological factors for prognostic and predictive indicators is not part of routine testing in ovarian cancer. As in other tumors, the detection of hematogenous tumor spread could help to estimate the risk of metastatic disease. We examined the expression of p53, KI67, topoisomerase IIalpha (Top IIa), epidermal growth factor receptor (EGFR), human epithelial growth factor receptor 2 (HER2) and nm23 in tumor tissues from 90 patients with ovarian cancer. All underwent bone marrow (BM) aspiration and screening for disseminated tumor cells in the bone marrow (DTC-BM) at primary diagnosis. BM aspiration, cytospin preparation, and immunocytochemical staining with the anticytokeratin antibody (A45-B/B3) were done following a standardized protocol. The expression of p53, KI67, Top IIa, EGFR, HER2, and nm23 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells or immunoreactive score (IRS). The prognostic impact of the individual factors together with standard histologic parameters was calculated by univariate and multivariate analyses. Expression rates for HER2 (2+/3+: 34.5%), KI67 (median 30%), p53 (median IRS 5), and Top IIa (median IRS 4) were relatively high, whereas nm23 (median IRS 2) and EGFR (IRS 0: 61%) showed weak staining. In 21/90 patients (23.3%), DTC-BM (>/=1/2 x 10(6) cells) could be detected. The presence of DTC-BM was inversely related to nodal status (P = .015) but not to the other factors examined. Tumor stage (P = .02), lymph node involvement (P = .003), grade (P = .046), postoperative tumor residue (P < .001), peritoneal seeding (P = .02), and KI67 (P = .046) significantly correlated with overall survival (OS) after a median observation time of 28 months (2-105). The finding of ascites was borderline significant (P = .050). The presence of DTC-BM (P = .04) and KI67 positivity (P = .02) predicted reduced distant disease-free survival. By multivariate analysis

  11. Prognostic Factors in Cholinesterase Inhibitor Poisoning

    PubMed Central

    Sun, In O; Yoon, Hyun Ju; Lee, Kwang Young

    2015-01-01

    Background Organophosphates and carbamates are insecticides that are associated with high human mortality. The purpose of this study is to investigate the prognostic factors affecting survival in patients with cholinesterase inhibitor (CI) poisoning. Material/Methods This study included 92 patients with CI poisoning in the period from January 2005 to August 2013. We divided these patients into 2 groups (survivors vs. non-survivors), compared their clinical characteristics, and analyzed the predictors of survival. Results The mean age of the included patients was 56 years (range, 16–88). The patients included 57 (62%) men and 35 (38%) women. When we compared clinical characteristics between the survivor group (n=81, 88%) and non-survivor group (n=11, 12%), there were no differences in renal function, pancreatic enzymes, or serum cholinesterase level, except for serum bicarbonate level and APACHE II score. The serum bicarbonate level was lower in non-survivors than in survivors (12.45±2.84 vs. 18.36±4.73, P<0.01). The serum APACHE II score was higher in non-survivors than in survivors (24.36±5.22 vs. 12.07±6.67, P<0.01). The development of pneumonia during hospitalization was higher in non-survivors than in survivors (n=9, 82% vs. n=31, 38%, P<0.01). In multiple logistic regression analysis, serum bicarbonate concentration, APACHE II score, and pneumonia during hospitalization were the important prognostic factors in patients with CI poisoning. Conclusions Serum bicarbonate and APACHE II score are useful prognostic factors in patients with CI poisoning. Furthermore, pneumonia during hospitalization was also important in predicting prognosis in patients with CI poisoning. Therefore, prevention and active treatment of pneumonia is important in the management of patients with CI poisoning. PMID:26411989

  12. The Expression of Multiple Proteins as Prognostic Factors in Colorectal Cancer: Cathepsin D, p53, COX-2, Epidermal Growth Factor Receptor, C-erbB-2, and Ki-67

    PubMed Central

    Shin, Il Yong; Sung, Na Young; Lee, Youn Soo; Kwon, Taek Soo; Si, Yoon; Lee, Yoon Suk; Oh, Seong Taek

    2014-01-01

    Background/Aims A single gene mutation alone cannot explain the poor prognosis of colorectal cancer. This study aimed to establish a correlation between the expression of six proteins and the prognosis of colorectal cancer patients. Methods Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer at our institution from January 2006 to December 2007. The expression of six proteins were determined using immunohistochemical staining of specimens. Results Cathepsin D, p53, COX-2, epidermal growth factor receptor, c-erbB-2, and Ki-67 expression were detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and colorectal cancer-specific survival (p=0.003), but the other expression levels were not. In a multivariate analysis, cathepsin D expression was found to be an independent prognostic factor for poorer colorectal cancer-specific survival (hazard ratio, 8.55; 95% confidence interval, 1.07 to 68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and colorectal cancer-specific survival rate (p=0.002). Conclusions Patients with cathepsin D positivity had a poorer outcome than patients who were cathepsin D-negative. Thus, cathepsin D may provide an indicator for appropriate intensive follow-up and adjuvant chemotherapy. PMID:24516696

  13. Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

    PubMed Central

    2012-01-01

    Background Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025). Conclusions Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC. PMID:23043286

  14. Prognostic Factors in Sudden Sensorineural Hearing Loss

    PubMed Central

    Atay, Gamze; Kayahan, Bahar; çınar, Betül çiçek; Saraç, Sarp; Sennaroğlu, Levent

    2016-01-01

    Background: Sudden sensorineural hearing loss (SSNHL) is still a complex and challenging process which requires clinical evidence regarding its etiology, treatment and prognostic factors. Therefore, determination of prognostic factors might aid in the selection of proper treatment modality. Aims: The aim of this study is to analyze whether there is correlation between SSNHL outcomes and (1) systemic steroid therapy, (2) time gap between onset of symptoms and initiation of therapy and (3) audiological pattern of hearing loss. Study Design: Retrospective chart review. Methods: Patients diagnosed at our clinic with SSNHL between May 2005 and December 2011 were reviewed. A detailed history of demographic features, side of hearing loss, previous SSNHL and/or ear surgery, recent upper respiratory tract infection, season of admission, duration of symptoms before admission and the presence of co-morbid diseases was obtained. Radiological and audiological evaluations were recorded and treatment protocol was assessed to determine whether systemic steroids were administered or not. Treatment started ≤5 days was regarded as “early” and >5 days as “delayed”. Initial audiological configurations were grouped as “upward sloping”, “downward sloping”, “flat” and “profound” hearing loss. Significant recovery was defined as thresholds improved to the same level with the unaffected ear or improved ≥30 dB on average. Slight recovery was hearing improvement between 10–30dB on average. Hearing recovery less than 10 dB was accepted as unchanged. Results: Among the 181 patients who met the inclusion criteria, systemic steroid was administered to 122 patients (67.4%), whereas 59 (32.6%) patients did not have steroids. It was found that steroid administration did not have any statistically significant effect in either recovered or unchanged hearing groups. Early treatment was achieved in 105 patients (58%) and 76 patients (42%) had delayed treatment. Recovery

  15. Ectopic expression of B and T lymphocyte attenuator in gastric cancer: a potential independent prognostic factor in patients with gastric cancer.

    PubMed

    Feng, Xing-Yu; Wen, Xi-Zhi; Tan, Xiao-Jing; Hou, Jing-Hui; Ding, Ya; Wang, Ke-Feng; Dong, Jun; Zhou, Zhi-Wei; Chen, Ying-Bo; Zhang, Xiao-Shi

    2015-01-01

    It has been confirmed that B and T lymphocyte attenuator (BTLA; also known as CD272) is a novel co--inhibitory molecule that exhibits a critical role in restraining cell-mediated antitumor immunity. The present study aimed to investigate the expression and prognostic significance of BTLA in gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed to investigate BTLA expression in gastric cancer tissues and normal mucosal tissues. In total, 123 pathologically confirmed specimens were obtained from stage IIIa gastric cancers. A correlation test, Kaplan-Meier curves, and a Cox proportional hazards regression model were used to analyze the data. No BTLA staining in the normal tissues was found, while BTLA-stained gastric carcinoma cells were detected in 75.6% (93/123) of the gastric cancer specimens. High expression levels of BTLA were detected in 31.7% (39/123) of the specimens, while low expression levels were detected in 68.3% (84/123) of the specimens. High BTLA expression levels were associated with shorter survival time, as confirmed by univariate and multivariate analyses. These findings provide a basis for the concept that high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer. PMID:25334051

  16. Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)

    PubMed Central

    Song, Guoqi; Ni, Huiyun; Zou, Linqing; Wang, Shukui; Tian, Fuliang; Liu, Hong; Cho, William C

    2016-01-01

    Objectives The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Design and methods The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates. Results The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB) type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS) and progression-free survival (PFS) in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. PMID:27382316

  17. The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma.

    PubMed

    Papanikolaou, X; Alapat, D; Rosenthal, A; Stein, C; Epstein, J; Owens, R; Yaccoby, S; Johnson, S; Bailey, C; Heuck, C; Tian, E; Joiner, A; van Rhee, F; Khan, R; Zangari, M; Jethava, Y; Waheed, S; Davies, F; Morgan, G; Barlogie, B

    2015-08-01

    As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ⩾65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein ⩾8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets. PMID:25753926

  18. The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma

    PubMed Central

    Papanikolaou, X; Alapat, D; Rosenthal, A; Stein, C; Epstein, J; Owens, R; Yaccoby, S; Johnson, S; Bailey, C; Heuck, C; Tian, E; Joiner, A; van Rhee, F; Khan, R; Zangari, M; Jethava, Y; Waheed, S; Davies, F; Morgan, G; Barlogie, B

    2015-01-01

    As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ⩾65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein ⩾8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets. PMID:25753926

  19. Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM) - correlation with prognostic factors

    PubMed Central

    Velazquez, Elsa F.; Jungbluth, Achim A.; Yancovitz, Molly; Gnjatic, Sacha; Adams, Sylvia; O'Neill, David; Zavilevich, Kira; Albukh, Tatyana; Christos, Paul; Mazumdar, Madhu; Pavlick, Anna; Polsky, David; Shapiro, Richard; Berman, Russell; Spira, Joanna; Busam, Klaus; Osman, Iman

    2007-01-01

    Cancer/testis (CT) antigens are potential targets for cancer immunotherapy, with NY-ESO-1 being among the most immunogenic. In several clinical trials in malignant melanoma (MM) patients, NY-ESO-1 protein/peptides showed clear evidence of inducing specific immunity. However, little is known about NY-ESO-1 expression in primary and metastatic MM and its relationship to disease progression. We analyzed NY-ESO-1 expression immunohistochemically in a series of primary and metastatic MMs and its relation to prognostic parameters and survival. We studied 61 primary and 63 metastatic MM specimens (from 61 and 56 patients, respectively). The prevalence of NY-ESO-1 expression was significantly higher in metastatic versus primary tumors [18/56 (32%) versus 8/61 (13%), P = 0.015]. There was a significant association between initial stage at presentation and NY-ESO-1 expression [stage I (3.45%), stage II (9.52%) and stage III (45.45%), P = 0.0014]. Primary MMs expressing NY-ESO-1 were significantly thicker than NY-ESO-1 negative cases (median thickness 4.7 mm versus 1.53 mm respectively, P = 0.03). No significant difference was seen in overall survival. In conclusion, NY-ESO-1 is more frequently expressed in metastatic than in primary MM and its expression is associated with thicker primary lesions and a higher frequency of metastatic disease, indicative of a worse prognosis. Our study suggests that patients with metastatic MM who express NY-ESO-1 may benefit from NY-ESO-1-based immunotherapy. PMID:17625806

  20. Nonrhabdomyosarcomatous abdominopelvic sarcomas: Analysis of prognostic factors

    PubMed Central

    Iqbal, Nida; Shukla, Nootan K.; Deo, S. V. S.; Agarwala, Sandeep; Sharma, D. N.; Sharma, Meher C.; Bakhshi, Sameer

    2016-01-01

    Background: Data concerning treatment outcome and prognostic factors in sarcomas of abdomen and pelvis are sparse in literature. Methods and Results: Of 696 patients with nonrhabdomyosarcomatous soft tissue sarcoma registered at our center between June 2003 and December 2012, 112 (16%) patients of sarcomas arising from abdomen and pelvis were identified, of which 88 patients were analyzed for treatment outcome and prognostic factors. The median age was 40 years (range: 1–78 years) with a male: female ratio of 0.7:1. Twenty-one (24%) patients were metastatic at baseline. The most common tumor sites were retroperitoneum in 70% patients and abdominal wall in 18% patients. Leiomyosarcoma was the most common histological subtype in 36% patients followed by liposarcoma in 17% patients. Thirty-five (40%) patients had Grade III tumors. Forty-six (52%) patients underwent surgical resection. At a median follow-up of 43 months (range: 2–94 months), the 5-year event-free survival (EFS) and overall survival (OS) were 35% and 42%, with a median of 22 months and 43 months, respectively. Multivariate analysis identified male gender (P - 0.03, hazard ratio [HR] - 0.46, 95% confidence interval [CI] - 0.23–0.92), baseline metastatic disease (P - 0.01, HR - 2.98, 95% CI - 1.27–6.98) and Grade III tumors (P - 0.02, HR - 1.84, 95% CI - 1.08–3.13) as factors associated with poor EFS, whereas baseline metastatic disease (P < 0.001, HR - 5.45, 95% CI - 2.31–12.87) and unresectability (P - 0.01, HR - 2.72, 95% CI - 1.27–5.83) were associated with poor OS. Conclusion: This is a single-institutional study of patients with abdominopelvic sarcomas where gender was identified as a new factor affecting survival apart from baseline presentation, histologic grade, and surgical resection. PMID:27168708

  1. Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma

    PubMed Central

    Wakai, Toshifumi; Shirai, Yoshio; Sakata, Jun; Matsuda, Yasunobu; Korit, Pavel V; Takamura, Masaaki; Ajioka, Yoichi; Hatakeyama, Katsuyoshi

    2011-01-01

    This study aimed to evaluate the association between the immunohistochemical expression of NAD(P) H:quinone oxidoreductase-1 (NQO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in resected specimens of intrahepatic cholangiocarcinoma (ICC) and to elucidate the prognostic value of NQO1 and Nrf2 expression. A retrospective analysis was conducted of 34 consecutive patients who underwent surgical resection for ICC. Immunohistochemistry of the resected specimens was conducted using each of the following primary monoclonal antibodies against NQO1 and Nrf2. Of the 34 patients, 23 were classified as having tumors with NQO1-positive expression and 11 had tumors with loss of NQO1 expression, whereas 22 patients had tumors with Nrf2-positive expression and 12 had tumors with loss of Nrf2 expression. NQO1 expression showed a positive association with Nrf2 expression (p=0.005). Loss of NQO1 expression was more frequent in tumor specimens that were moderately or poorly differentiated (11/26; 42%) than in well-differentiated tumors (0/8; 0%; p=0.034). Post-resection survival was significantly worse in patients with tumors with loss of NQO1 expression than in patients with NQO1-positive tumors (cumulative 5 -year survival rate of 0% and 51%, respectively; p=0.005). Nrf2 expression was not associated with survival after resection (p=0.287). The Cox proportional hazards regression analysis revealed that lymph node involvement (p<0.001) and loss of NQO1 expression (p<0.001) had an independent adverse effect on survival. Loss of NQO1 expression reflects dedifferentiation and thus indicates a poor prognosis for patients undergoing resection for ICC. PMID:21577322

  2. Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer.

    PubMed

    Jia, Xiao-Qin; Zhang, Shu; Zhu, Hui-Jun; Wang, Wei; Zhu, Jin-Hong; Wang, Xu-Dong; Qiang, Jian-Feng

    2016-06-01

    Phosphoglycerate dehydrogenase (PHGDH) plays an essential role in cancer-specific metabolic reprogramming. It has been reported as a putative metabolic oncogene in several types of human malignant tumors, such as breast cancer and melanoma. To date, PHGDH expression in colorectal cancer (CRC) as well as its association with clinicopathological characteristics and prognostic implication remain undetermined. In this study, we determined the PHGDH protein expression using tissue microarray immunohistochemistry (TMA-IHC) on 193 pairs of formalin-fixed, paraffin-embedded specimens of CRC and adjacent tissues, 25 chronic colitis, 41 low-, and 19 high-grade intraepithelial neoplasia specimens, and we also determined PHGDH mRNA level using quantitative reverse transcription PCR (qRT-PCR) on additional 23 pairs of fresh CRC tissues and adjacent tissues. We found that both PHGDH mRNA and protein was highly expressed in tumor tissues in comparison with matched adjacent non-tumor tissues, and high PHGDH protein expression was correlated with advanced TNM stage (P = .038) and larger tumor (P = .001). Multivariate Cox regression analysis showed that PHGDH protein expression (HR = 2.285, 95% CI = 1.18 to 4.41, P = .014), tumor differentiation (HR = .307, 95% CI = .154 to 0.609, P = .001), and TNM stage (HR = 1.791, 95% CI = 1.125 to 2.85, P = .014) were independent prognostic factors in CRC. Kaplan-Meier survival curves and log rank test showed that high PHGDH protein expression contributed to poor outcome in CRC patients (P < .001). In conclusion, these results suggest that assessment of PHGDH expression could be useful in identifying a high-risk subgroup of CRC. PMID:27267836

  3. Prognostic factors and classification in multiple myeloma.

    PubMed Central

    San Miguel, J. F.; Sànchez, J.; Gonzalez, M.

    1989-01-01

    Analyses of prognostic factors have allowed the design of staging systems in different haematological disorders. In a series of 220 patients with multiple myeloma, univariate analysis showed that nine parameters had a significant adverse effect on survival; poor performance status (Karnowsky scaling system less than 70%), infections before diagnosis, renal impairment (assessed either by creatinine clearance greater than 2 mg dl-1 or urea greater than 40 mg dl-1), serum calcium (greater than 10 mg dl-1), severe anaemia (less than 8.5 g dl-1), the presence of Bence-Jones proteinuria, failure to achieve complete remission, more than 40% plasma cells in bone marrow and a low paraprotein index (monoclonal component/% plasma cells: P less than 0.09). In addition, this index correlated significantly with all the other prognostic factors except performance status. The best combination of disease characteristics selected by means of the Cox regression proportional hazards method were performance status and creatinine levels. Additionally, by factor analysis of principal components we obtained a regression equation that included creatinine levels, haemoglobin, performance status and paraprotein index. Using this it was possible to separate the series of patients into three risk categories: A (65 patients), B (69 patients) and C (65 patients) with a median survival of 41, 24 and 12 months, respectively. The model provided similar results to those of the British Medical Research Council, whereas the staging systems proposed by Durie and Salmon, Merlin et al. and Carbone et al. had a lower discriminant value in our series. PMID:2757917

  4. A consensus prognostic gene expression classifier for ER positive breast cancer

    PubMed Central

    Teschendorff, Andrew E; Naderi, Ali; Barbosa-Morais, Nuno L; Pinder, Sarah E; Ellis, Ian O; Aparicio, Sam; Brenton, James D; Caldas, Carlos

    2006-01-01

    Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors. PMID:17076897

  5. Sudden Sensorineural Hearing Loss; Prognostic Factors

    PubMed Central

    Arjun, Dass; Neha, Goel; Surinder K, Singhal; Ravi, Kapoor

    2015-01-01

    Introduction: Sudden sensorineural hearing loss (SSNHL) is a frightening and frustrating symptom for the patient as well as the physician. Prognosis is affected by multiple factors including duration of hearing loss, presence of associated vertigo and tinnitus, and co-morbidities such as hypertension and diabetes. Materials and Methods: Forty subjects presenting to our department with features of sudden hearing loss were included in the study. Detailed otological history and examination, serial audiometric findings and course of disease were studied. Results: Subjects presenting late (in older age), having associated vertigo, hypertension and diabetes had a significantly lower rate of recovery. Conclusion: Only 60–65% of patients experiencing SSNHL recover within a period of 1 month; this rate is further affected by presence of multiple prognostic indicators. PMID:26568939

  6. PD-L1 expression on neoplastic or stromal cells is respectively a poor or good prognostic factor for adult T-cell leukemia/lymphoma.

    PubMed

    Miyoshi, Hiroaki; Kiyasu, Junichi; Kato, Takeharu; Yoshida, Noriaki; Shimono, Joji; Yokoyama, Shintaro; Taniguchi, Hiroaki; Sasaki, Yuya; Kurita, Daisuke; Kawamoto, Keisuke; Kato, Koji; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi

    2016-09-01

    Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7.4% of patients), and the other showed minimal expression in lymphoma cells (nPD-L1(-), 92.6%). Within the nPD-L1(-) group, 2 subsets emerged: the first displayed abundant PD-L1 expression in nonmalignant stromal cells of the tumor microenvironment (miPD-L1(+), 58.5%) and the second group did not express PD-L1 in any cell (PD-L1(-), 34.1%). nPD-L1(+) ATLL (median survival time [MST] 7.5 months, 95% CI [0.4-22.3]) had inferior overall survival (OS) compared with nPD-L1(-) ATLL (MST 14.5 months, 95% CI [10.1-20.0]) (P = .0085). Among nPD-L1(-) ATLL, miPD-L1(+) ATLL (MST 18.6 months, 95% CI [11.0-38.5]) showed superior OS compared with PD-L1(-) ATLL (MST 10.2 months, 95% CI [8.0-14.7]) (P = .0029). The expression of nPD-L1 and miPD-L1 maintained prognostic value for OS in multivariate analysis (P = .0322 and P = .0014, respectively). This is the first report describing the clinicopathological features and outcomes of PD-L1 expression in ATLL. More detailed studies will disclose clinical and biological significance of PD-L1 expression in ATLL. PMID:27418641

  7. Prognostic factors for sperm retrieval in non-obstructive azoospermia.

    PubMed

    Glina, Sidney; Vieira, Marcelo

    2013-01-01

    Testicular sperm retrieval techniques associated with intracytoplasmic sperm injection have changed the field of male infertility treatment and given many azoospermic men the chance to become biological fathers. Despite the current use of testicular sperm extraction, reliable clinical and laboratory prognostic factors of sperm recovery are still absent. The objective of this article was to review the prognostic factors and clinical use of sperm retrieval for men with non-obstructive azoospermia. The PubMed database was searched for the Medical Subject Headings (MeSH) terms azoospermia, sperm retrieval, and prognosis. Papers on obstructive azoospermia were excluded. The authors selected articles that reported successful sperm retrieval techniques involving clinical, laboratory, or parenchyma processing methods. The selected papers were reviewed, and the prognostic factors were discussed. No reliable positive prognostic factors guarantee sperm recovery for patients with non-obstructive azoospermia. The only negative prognostic factor is the presence of AZFa and AZFb microdeletions. PMID:23503961

  8. Minimally invasive follicular thyroid carcinomas: prognostic factors.

    PubMed

    Stenson, Gustav; Nilsson, Inga-Lena; Mu, Ninni; Larsson, Catharina; Lundgren, Catharina Ihre; Juhlin, C Christofer; Höög, Anders; Zedenius, Jan

    2016-08-01

    Although minimally invasive follicular thyroid carcinoma (MI-FTC) is regarded as an indolent tumour, treatment strategies remain controversial. Our aim was to investigate the outcome for patients with MI-FTC and to identify prognostic parameters to facilitate adequate treatment and follow-up. This retrospective follow-up study involved all cases of MI-FTC operated at the Karolinska University Hospital between 1986 and 2009. Outcome was analysed using death from MI-FTC as endpoint. Fifty-eight patients (41 women and 17 men) with MI-FTC were identified. The median follow-up time was 140 (range 21-308) months. Vascular invasion was observed in 36 cases and was associated with larger tumour size [median 40 (20-76) compared with 24 (10-80) mm for patients with capsular invasion only (P = 0.001)] and older patients [54 (20-92) vs. 44 (11-77) years; P = 0.019]. Patients with vascular invasion were more often treated with thyroidectomy (21/36 compared to 7/22 with capsular invasion only; P = 0.045). Five patients died from metastatic disease of FTC after a median follow-up of 114 (range 41-193) months; all were older than 50 years (51-72) at the time of the initial surgery; vascular invasion was present in all tumours and all but one were treated with thyroidectomy. Univariate analysis identified combined capsular and vascular invasion (P = 0.034), age at surgery ≥50 years (P = 0.023) and male gender (P = 0.005) as related to risk of death from MI-FTC. MI-FTC should not be considered a purely indolent disease. Age at diagnosis and the existence of combined capsular and vascular invasion were identified as important prognostic factors. PMID:26858184

  9. Prognostic factors in patients with intracerebral haematoma.

    PubMed Central

    Franke, C L; van Swieten, J C; Algra, A; van Gijn, J

    1992-01-01

    In a prospective study, the prognostic value of clinical characteristics in 157 consecutive patients with spontaneous supratentorial intracerebral haemorrhage were examined by means of multivariate analysis. Two days after the event 37 (24%) patients had died. Factors independently contributing to the prediction of two day mortality were pineal gland displacement on CT of 3 mm or more (p less than 0.001), blood glucose level on admission of 8.0 mmol/l or more (p = 0.01), eye and motor score on the Glasgow Coma Scale of eight out of 10 or less (p = 0.022) and haematoma volume of 40 cm3 or more (p = 0.037). Between the third day and one year after the event another 46 of the 120 two day survivors had died; the independent prognostic indicators for death during that period were: age 70 years or more (p less than 0.001) and severe handicap (Rankin grade five) on the third day (p less than 0.001). Functional independence (Rankin grade two or less) at one year was most common not only with the converse features of age less than 70 years (p less than 0.01) and Rankin grade four or less on the third day (p = 0.002), but also with an eye and motor score on the Glasgow Coma Scale of nine or 10 on the third day (p less than 0.001). The 120 patients with intracerebral haemorrhage who were still alive two days after the event were matched with 120 patients with cerebral infarction, according to age, level of consciousness on the third day after stroke (Glasgow Coma Scale) and handicap (Rankin grade). Survival and handicap after one year did not differ between these two groups. The conclusion drawn is that it is not the cause (intracerebral haemorrhage or cerebral infarction) but the extent of the brain lesion that determines the outcome in patients who survive the first two days. PMID:1527534

  10. Interleukin-33 in human gliomas: Expression and prognostic significance

    PubMed Central

    GRAMATZKI, DOROTHEE; FREI, KARL; CATHOMAS, GIERI; MOCH, HOLGER; WELLER, MICHAEL; MERTZ, KIRSTEN DIANA

    2016-01-01

    Interleukin-33 (IL-33) is a nuclear and pleiotropic cytokine with regard to its cellular sources and its actions. IL-33 is involved in the pathogenesis of brain diseases. Several factors account for the tumorigenicity of human gliomas, including cytokines and their receptors. The present study assessed the expression and prognostic significance of IL-33 in human astroglial brain tumors. Protein levels of IL-33 were determined by immunohistochemistry using a tissue microarray containing 95 human gliomas. mRNA expression data of IL-33, as well as of its receptors, IL-1 receptor-like 1 protein and IL-1 receptor accessory protein (IL1RAcP), were obtained from The Cancer Genome Atlas database. IL-33 protein was expressed heterogeneously in tumor tissue, but was, however, not detected in normal brain tissue. There was no differential IL-33 protein expression by tumor grade, while IL-33 protein expression was associated with inferior survival in patients with recurrent glioblastomas. Interrogations of the TCGA database indicated that mRNA expression of IL-33 and the IL-33 receptors was heterogeneous, and that IL-33 and IL1RAcP mRNA levels were correlated with the tumor grade. Elevated IL-33 mRNA levels were associated with the inferior survival of glioblastoma patients. Therefore, IL-33 may play an important role in the pathogenesis and prognosis of human gliomas. PMID:27347163

  11. Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma

    PubMed Central

    CHEN, YONG; ZHU, SHUANG-MEI; XU, XIAO-LING; ZHAO, AN; HU, JIN-LIN

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is the eighth most frequent neoplasm in China. However, the expression levels of human epidermal growth factor receptor 2 (HER2) and multidrug resistance protein 1 (MRP1) in patients with ESCC remain to be determined. In the present study, 829 ESCC cases were evaluated using immunohistochemistry. The association between the expression levels of HER2 and MRP1 and the patient's clinicopathological factors was analyzed using Fisher's exact test or χ2 test. Univariate analysis was performed via Kaplan-Meier survival curves, while the Cox proportional hazard model was used for multivariate analysis. A significant correlation was observed between the expression levels of HER2 and the patient's gender (P<0.050), tumor size (P=0.013) and venous/lymphatic invasion (P=0.039). However, no significant correlation was identified between the expression levels of MRP1 and the clinicopathological factors of the patients. In univariate analysis, gender, differentiation, depth of invasion, clinical stage, adjuvant radiotherapy or chemotherapy and lymph node metastasis were significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients with ESCC (P<0.050). The graphical representation of the Kaplan-Meier estimate curves suggested that the expression levels of HER2 or MRP1 did not exert any influence on prognosis (log-rank test, P>0.050). In multivariate analysis, tumor location, gender, clinical stage, differentiation and lymph node metastasis were identified as independent factors of prognosis in patients with ESCC (P<0.050). However, the expression levels of HER2 or MRP1 were not independently associated with PFS or OS in these patients. In conclusion, the present large-scale study demonstrates that the protein expression levels of HER2 and MRP1 does not exert any influence on the prognosis of ESCC. PMID:26870278

  12. Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients.

    PubMed

    Surowiak, Paweł; Materna, Verena; Kaplenko, Irina; Spaczyński, Marek; Dietel, Manfred; Lage, Hermann; Zabel, Maciej

    2005-09-01

    Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients. PMID:15968547

  13. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  14. Expression and prognostic significance of apolipoprotein D in breast cancer.

    PubMed Central

    Díez-Itza, I.; Vizoso, F.; Merino, A. M.; Sánchez, L. M.; Tolivia, J.; Fernández, J.; Ruibal, A.; López-Otín, C.

    1994-01-01

    Apolipoprotein D (apo D) is a glycoprotein involved in the human plasma lipid transport system and present at large amounts in cyst fluid from women with gross cystic disease of the breast. Apo D expression in breast carcinomas was examined by immunoperoxidase staining of a series of 163 tumors. A total of 60 (36.8%) tumors were negative for apo D immunostaining, 28 (17.2%) carcinomas were weakly positive, 33 (20.2%) were moderately stained, whereas the remaining 42 (25.8%) tumors were strongly stained with the specific antibodies. No significant correlation was found between apo D content and tumor size, lymph node involvement, or biochemical parameters such as estrogen receptors, cathepsin D, or pS2 protein. However, the finding of a significant association between apo D and menopausal status of patients or differentiation grade of tumors, with apo D values being lower in tumors from premenopausal women or in poorly differentiated carcinomas, suggested a potential value of this glycoprotein as a prognostic factor in breast cancer. Preliminary analysis of relapse-free survival and overall survival in a subgroup of 152 women with a mean follow-up of 42 months confirmed that low apo D values were significantly associated to a shorter relapse-free survival and poorer survival. According to these data, we propose that apo D in combination with other well-established prognostic factors may contribute to more accurately identify subgroups of breast cancer patients with low or high risk for relapse and death. Images Figure 1 Figure 2 Figure 3 PMID:8311115

  15. Prognostic significance of X-ray cross-complementing gene 1 expression in gastric cancer

    PubMed Central

    Wang, Jian; Wang, Tongshan; Xu, Jun; Chen, WenJiao; Shi, Wei; Cheng, Jianfeng

    2016-01-01

    Objective The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCC1) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods Immunohistochemistry (IHC) was used to evaluate XRCC1 protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Among 612 patients staged Ⅱ/Ⅲ in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P = 0.347) or DFS (P = 0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P = 0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P = 0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P < 0.05). Though XRCC1 plays an important role in DNA repair pathways, no significant relationship is found in XRCC1 expression and OS among gastric cancer in our study. Conclusions XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy.

  16. The prognostic significance of survivin expression in gallbladder carcinoma.

    PubMed

    Salman, Tarik; Argon, Asuman; Kebat, Tulu; Vardar, Enver; Erkan, Nazif; Alacacıoğlu, Ahmet

    2016-08-01

    Gallbladder cancers (GBC) are characterized by rapid progression, early metastasis, and poor prognosis; the molecular mechanisms of the various signaling pathways involved should be elucidated to develop effective therapies. Survivin, an apoptosis inhibitor protein expressed in the G2/M phase of the cell cycle, plays a role in cell division and affects both cell survival and proliferation. Survivin has been investigated in many types of cancer, and this study aims to examine the relationship of survivin expression in gallbladder cancer patients with clinicopathological features and prognosis. We evaluated demographic characteristics (age, gender), tumor characteristics (histopathological type, differentiation, perineural, and lymphovascular invasion; serosal invasion, surgical margin positivity and lymphocytic response), and Survivin expression immunohistochemically, and we analysed the relationship between these characteristics and prognosis in 47 gallbladder carcinoma cases from 2000 to 2011. Immunohistochemically, while survivin expression was observed in 36 cases, it was absent in 11 cases. Follow-up data were obtained from 32 patients. Two (8.7%) of 23 cases with a Survivin-positive tumor were alive at 74th and 35th months, whereas 5 (%55.6) of nine cases with Survivin-negative tumor were alive at 50th, 89th, 124th, 126th, 131th months. Survivin expression was correlated with short survival (p = 0.043), and the univariate analysis showed that reduced overall survival was associated with age (p = 0.043), male gender (p = 0.038), infiltrative pattern (p = 0.019), lymphovascular invasion (p = 0.004), perineural invasion (p = 0.009), serosal invasion (p = 0.027), ulcer (p = 0.033), and surgical margin positivity (p = 0.022). Despite the low number of patients in our study, the analysis results suggest that survivin positivity might actually be a significant prognostic factor. This finding could be a reference point for targeted treatment studies. However, further

  17. Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients.

    PubMed

    Dielmann, Anastasia; Letsch, Anne; Nonnenmacher, Anika; Miller, Kurt; Keilholz, Ulrich; Busse, Antonia

    2016-02-01

    T-box transcription factors, T-box expressed in T cells (T-bet) encoded by Tbx21 and Eomesodermin (Eomes), drive the differentiation of effector/memory T cell lineages and NK cells. The aim of the study was to determine the prognostic influence of the expression of these transcription factors in peripheral blood (pB) in a cohort of 41 metastatic (m) RCC patients before receiving sorafenib treatment and to analyze their association with the immunophenotype in pB. In contrast to Tbx21, in the multivariate analysis including clinical features, Eomes mRNA expression was identified as an independent good prognostic factor for progression-free survival (PFS, p = 0.042) and overall survival (OS, p = 0.001) in addition to a favorable ECOG performance status (p = 0.01 and p = 0.008, respectively). Eomes expression correlated positively not only with expression of Tbx21 and TGFβ1 mRNA, but also with mRNA expression of the activation marker ICOS, and with in vivo activated HLA-DR(+) T cells. Eomes expression was negatively associated with TNFα-producing T cells. On protein level, Eomes was mainly expressed by CD56(+)CD3(-) NK cells in pB. In conclusion, we identified a higher Eomes mRNA expression as an independent good prognostic factor for OS and PFS in mRCC patients treated with sorafenib. PMID:26753694

  18. Molecular predictive and prognostic factors in ependymoma.

    PubMed

    Benson, Rony; Mallick, Supriya; Julka, Pramod K; Rath, Goura K

    2016-01-01

    An ependymoma is an uncommon glial tumor, which arises from different parts of the neuroaxis. Considerable variation in presentation and survival in tumors in different locations after an optimum treatment indicates inherent molecular and genetic differences in tumorigenesis between them. A number of genetic aberrations have been identified to distinctly characterize different subgroups of ependymomas that include a posterior fossa tumor, a supratentorial tumor, and a pediatric tumor. These different groups have substantial genetic alterations, and also distinct demography, clinical characteristics, and prognosis. This article is intended to review the diverse molecular and genetic aberrations that may be helpful in prognostication and prediction of survival in patients suffering from an ependymoma. PMID:26954807

  19. Recent Advancements in Prognostic Factors of Epithelial Ovarian Carcinoma

    PubMed Central

    Ezzati, Mohammad; Abdullah, Amer; Shariftabrizi, Ahmad; Hou, June; Kopf, Michael; Stedman, Jennifer K.; Samuelson, Robert; Shahabi, Shohreh

    2014-01-01

    Ovarian cancer remains the most common cause of gynecologic cancer-related death among women in developed countries. Nevertheless, subgroups of ovarian cancer patients experience relatively longer survival. Efforts to identify prognostic factors that characterize such patients are ongoing, with investigational areas including tumor characteristics, surgical management, inheritance patterns, immunologic factors, and genomic patterns. This review discusses various demographic, clinical, and molecular factors implicating longevity and ovarian cancer survival. Continued efforts at identifying these prognosticators may result in invaluable adjuncts to the treatment of ovarian cancer, with the ultimate goal of advancing patient care.

  20. Preoperative radiotherapy for rectal adenocarcinoma: Which are strong prognostic factors?

    SciTech Connect

    Chapet, Olivier . E-mail: ochapet@med.umich.edu; Romestaing, Pascale; Mornex, Francoise; Souquet, Jean-Christophe; Favrel, Veronique; Ardiet, Jean-Michel; D'Hombres, Anne; Gerard, Jean-Pierre

    2005-04-01

    Purpose: This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors. Methods and Materials: Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen. Results: The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p < 0.001) and cN stage (p < 0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p < 0.014) but not for uN (p < 0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p < 0.001 and p < 0.001, respectively). Conclusion: Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.

  1. Course and Prognostic Factors for Neck Pain in Workers

    PubMed Central

    Hogg-Johnson, Sheilah; Côté, Pierre; van der Velde, Gabrielle; Holm, Lena W.; Carragee, Eugene J.; Hurwitz, Eric L.; Peloso, Paul M.; Cassidy, J. David; Guzman, Jaime; Nordin, Margareta; Haldeman, Scott

    2008-01-01

    Study Design Best-evidence synthesis. Objective To perform a best evidence synthesis on the course and prognostic factors for neck pain and its associated disorders in workers. Summary of Background Data Knowledge of the course of neck pain in workers guides expectations for recovery. Identifying prognostic factors assists in planning effective workplace policies, formulating interventions and promoting lifestyle changes to decrease the frequency and burden of neck pain in the workplace. Methods The Bone and Joint Decade 2000−2010 Task Force on Neck Pain and its Associated Disorders (Neck Pain Task Force) conducted a critical review of the literature published between 1980 and 2006 to assemble the best evidence on neck pain and its associated disorders. Studies meeting criteria for scientific validity were included in a best evidence synthesis. Results We found 226 articles related to course and prognostic factors in neck pain and its associated disorders. After a critical review, 70 (31%) were accepted on scientific merit; 14 of these studies related to course and prognostic factors in working populations. Between 60% and 80% of workers with neck pain reported neck pain1 year later. Few workplace or physical job demands were identified as being linked to recovery from neck pain. However, workers with little influence on their own work situation had a slightly poorer prognosis, and white-collar workers had a better prognosis than blue-collar workers. General exercise was associated with better prognosis; prior neck pain and prior sick leave were associated with poorer prognosis. Conclusion The Neck Pain Task Force presents a report of current best evidence on course and prognosis for neck pain. Few modifiable prognostic factors were identified; however, having some influence over one's own job and being physically active seem to hold promise as prognostic factors.

  2. Prognostic factors in early-stage leiomyosarcoma of the uterus.

    PubMed

    Pelmus, Manuela; Penault-Llorca, Frédérique; Guillou, Louis; Collin, Françoise; Bertrand, Gérard; Trassard, Martine; Leroux, Agnès; Floquet, Anne; Stoeckle, Eberhard; Thomas, Laurence; MacGrogan, Gaëtan

    2009-04-01

    Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 x 10). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome. PMID:19407564

  3. Prognostic and Biological Significance of MicroRNA-127 Expression in Human Breast Cancer

    PubMed Central

    Wang, Shaohua; Li, Hanjun; Wang, Jingjie; Wang, Dan; Yao, Anlong; Li, Qiurong

    2014-01-01

    The purpose of this study was to determine the expression of miR-127 and analyze its prognostic and biological significance in breast cancer (BC). A quantitative reverse transcription PCR assay was performed to detect the expression of miR-127 in 15 pairs of BC and corresponding noncancerous tissues. The expression of miR-127 was detected in another 110 BC tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of miR-127 expression. The effects of miR-127 expression on malignant phenotypes of BC cells and its possible molecular mechanisms were further determined. miR-127 was significantly downregulated in BC tissues, and low miR-127 expression was significantly correlated with lymph node metastasis and advanced clinical stage. Patients with low miR-127 showed poorer overall survival than those with high miR-127. Multivariate analyses indicated that status of miR-127 was an independent prognostic factor for patients. Functional analyses showed that upregulation of miR-127 significantly inhibited growth, enhanced apoptosis, and reduced migration and invasion in BC cells by targeting the protooncogene BCL-6. Therefore, miR-127 may be a potential biomarker for predicting the survival of BC patients and might be a molecular target for treatment of human BCs. PMID:25477702

  4. Moderate level of HER2 expression and its prognostic significance in breast cancer with intermediate grade.

    PubMed

    Ignatov, Tanja; Eggemann, Holm; Burger, Elke; Fettke, Franziska; Costa, Serban Dan; Ignatov, Atanas

    2015-06-01

    Overexpression of human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive marker of response to anti-HER2 therapy in breast cancer. Our goal was to analyze the prognostic significance of moderate expression of HER2 in breast cancer with intermediate differentiation grade. We performed a multicenter retrospective register study of 8494 patients with primary non-metastatic breast cancer admitted between 2000 and 2011 to eight Clinics in Saxony-Anhalt, federal state of Germany. Patients were divided into three groups according to their HER2 score: 4073 were classified as HER2 negative (HER2 0 and 1+), 822 HER2 moderate (HER2 2+/HER2), and 1238 HER2 positive (HER2 3+ or HER2 2+/HER2+). HER2-positive cases were excluded from analysis. Tumors with moderate HER2 (HER2 2+) expression demonstrated an aggressive behavior and worse patient survival compared with HER2 0 and 1+ status. HER2 2+ status was associated with shorter median overall survival (OS) (P < 0.0001) in breast cancer patients with an intermediate grade of differentiation. Comparing low-grade and high-grade tumors, HER2 moderate expression did not significantly influence patient survival. In multivariate analysis after adjustment for other prognostic factors HER2 2+ status remained an unfavorable prognostic factor for OS (HR 1.224, 95 % CI 1.059-1.415, P = 0.006) in breast cancer patients with an intermediate grade of differentiation. HER2 2+ status is an unfavorable prognostic factor regarding the OS of breast cancer patients with intermediate grade of differentiation and could be used to identify patients, who may benefit from adjuvant therapy. PMID:25926338

  5. Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival

    PubMed Central

    2015-01-01

    Objective To evaluate the relationship between the expression profiles of 84 extracellular matrix (ECM) genes and the prognosis of patients with colorectal cancer (CRC). Methods This retrospective study included 114 patients with stage I–IV CRC who underwent primary tumour resection. Quantitative real-time PCR and immunohistochemistry assays were conducted using primary tumour samples. Kaplan-Meier survival curves were also generated to identify differences in global survival (GS) and disease-free survival (DFS) for the hypo- or hyperexpression status of each marker. The log-rank test was used to verify whether the differences were significant. Stepwise Cox regression models were also used to identify the risk factors associated with GS and DFS in a multivariate mode, and then were used to score the risk of death associated with each marker, either independently or in association. Results In the univariate analyses, significant differences in GS in relation to the expression profiles of ITGAV (p = 0.001), ITGA3 (p = 0.002), ITGA6 (p = 0.001), SPARC (p = 0.036), MMP9 (p = 0.034), and MMP16 (p = 0.038) were observed. For DFS, significant differences were observed in associated with ITGAV (p = 0.004) and ITGA3 (p = 0.001). However, only the ITGAV and ITGA6 gene markers for GS (hazard ratio (HR) = 3.209, 95% confidence interval (CI) = 1.412–7.293, p = 0.005 and HR = 3.105, 95% CI = 1.367–7.055, p = 0.007, respectively), and ITGA3 for DFS (HR = 3.806, 95% CI = 1.573–9.209, p = 0.003), remained in the final Cox regression models. A scoring system was developed to evaluate the risk of patient death based on the number of markers for the components of the final GS model. Scores of 0, 1, or 2 were associated with the following mean survival rates [CI]: 47.162 [44.613–49.711], 39.717 [35.471–43.964], 30.197 [24.030–36.327], respectively. Conclusions Multivariate mathematical models demonstrated an association between hyperexpression of the ITGAV and ITGA6

  6. Cyclin D1 amplification and expression in human breast carcinoma: correlation with histological prognostic markers and oestrogen receptor expression

    PubMed Central

    Worsley, S D; Jennings, B A; Khalil, K H; Mole, M; Girling, A C

    1996-01-01

    Aims—To study the amplification of the Cyclin D1 gene (CCND1) in human breast carcinoma; to relate this to Cyclin D1 protein expression; to relate these parameters to recognised pathological prognostic factors, including oestrogen receptor (ER) status. Methods—DNA extracted from frozen sections of breast tumours (n = 36) was used for Southern blotting. Probes for CCND1, c-myc and the immunoglobulin heavy chain locus (IgH) were hybridised to tumour DNA. Immunocytochemical expression of Cyclin D1 protein and ER was studied in paraffin wax sections from the same tumours. Results—Amplification of CCND1 was observed in 11% (four of 36) of tumours studied. Over expression of Cyclin D1 protein was observed in 73% (30/41) of tumours. There was no correlation between recognised histological prognostic markers and either gene amplification or expression. However, a weak association was seen between Cyclin D1 expression and ER status. Conclusions—A disparity exists between locus amplification and over expression of Cyclin D1, suggesting the existence of another mechanism for raised protein expression. No significant correlation was detected between either Cyclin D1 amplification or over expression and established prognostic markers. Images PMID:16696045

  7. Gender differences in prognostic factors for oral cancer.

    PubMed

    Honorato, J; Rebelo, M S; Dias, F L; Camisasca, D R; Faria, P A; Azevedo e Silva, G; Lourenço, S Q C

    2015-10-01

    The aim of this study was to assess gender differences in prognostic factors among patients treated surgically for oral squamous cell carcinoma (OSCC). The medical records of 477 eligible patients (345 males, 132 females) obtained from the Brazilian Cancer Institute were reviewed. Survival was calculated by Kaplan-Meier method. Cox regression models were used to obtain adjusted hazard ratios (aHR) for males and females. Multivariate analysis showed that past tobacco use (aHR 0.2, 95% confidence interval (CI) 0.1-0.7) and regional metastasis (aHR 2.3, 95% CI 1.5-3.5) in males, and regional metastasis (aHR 2.2, 95% CI 1.2-4.3), distant metastasis (aHR 6.7, 95% CI 1.3-32.7), and hard palate tumours (aHR 11.8, 95% CI 3.3-47.7) in females, were associated with a higher risk of death. There were no differences in survival between males and females. Regional metastasis was found to be a negative prognostic factor in OSCC for both genders. Past tobacco use was an independent prognostic factor for worse survival among males, while distant metastasis and hard palate tumours were independent prognostic factors for worse survival among females. Further studies are necessary to corroborate the relationships found in this study. PMID:26183881

  8. Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

    PubMed Central

    Mofleh, Ibrahim A Al

    2008-01-01

    Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis (SAP). An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as effective as multifactorial scoring systems (MFSS) at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen (BUN), creatinine, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis (PN), infected PN (IPN) and mortality. PMID:18205255

  9. WDR5 Expression Is Prognostic of Breast Cancer Outcome

    PubMed Central

    Zhan, Chunjun; Liu, Xiuxia; Bai, Zhonghu; Yang, Yankun

    2015-01-01

    WDR5 is a core component of the human mixed lineage leukemia-2 complex, which plays central roles in ER positive tumour cells and is a major driver of androgen-dependent prostate cancer cell proliferation. Given the similarities between breast and prostate cancers, we explore the potential prognostic value of WDR5 gene expression on breast cancer survival. Our findings reveal that WDR5 over-expression is associated with poor breast cancer clinical outcome in three gene expression data sets and BreastMark. The eQTL analysis reveals 130 trans-eQTL SNPs whose genes mapped with statistical significance are significantly associated with patient survival. These genes together with WDR5 are enriched with “cellular development, gene expression, cell cycle” signallings. Knocking down WDR5 in MCF7 dramatically decreases cell viability, but does not alter tumour cell response to doxorubicin. Our study reveals the prognostic value of WDR5 expression in breast cancer which is under long-range regulation of genes involved in cell cycle, and anthracycline could be coupled with treatments targeting WDR5 once such a regimen is available. PMID:26355959

  10. AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial

    PubMed Central

    Gnosa, S; Zhang, H; Brodin, V P; Carstensen, J; Adell, G; Sun, X-F

    2014-01-01

    Background: Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties. Methods: The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay. Results: The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P=0.009) and worse disease-free survival (P=0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines. Conclusions: The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse. PMID:24874474

  11. Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma.

    PubMed

    Vavougios, Georgios D; Solenov, Evgeniy I; Hatzoglou, Chrissi; Baturina, Galina S; Katkova, Liubov E; Molyvdas, Paschalis Adam; Gourgoulianis, Konstantinos I; Zarogiannis, Sotirios G

    2015-10-01

    The aim of our study was to assess the differential gene expression of Parkinson protein 7 (PARK7) interactome in malignant pleural mesothelioma (MPM) using data mining techniques to identify novel candidate genes that may play a role in the pathogenicity of MPM. We constructed the PARK7 interactome using the ConsensusPathDB database. We then interrogated the Oncomine Cancer Microarray database using the Gordon Mesothelioma Study, for differential gene expression of the PARK7 interactome. In ConsensusPathDB, 38 protein interactors of PARK7 were identified. In the Gordon Mesothelioma Study, 34 of them were assessed out of which SUMO1, UBC3, KIAA0101, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7, HTRA2, and STUB1 were significantly overexpressed whereas TRAF6 and MTA2 were significantly underexpressed in MPM patients (network 2). Furthermore, Kaplan-Meier analysis revealed that MPM patients with high BBS1 expression had a median overall survival of 16.5 vs. 8.7 mo of those that had low expression. For validation purposes, we performed a meta-analysis in Oncomine database in five sarcoma datasets. Eight network 2 genes (KIAA0101, HDAC2, SUMO1, RBBP4, NONO, RBBP7, HTRA2, and MTA2) were significantly differentially expressed in an array of 18 different sarcoma types. Finally, Gene Ontology annotation enrichment analysis revealed significant roles of the PARK7 interactome in NuRD, CHD, and SWI/SNF protein complexes. In conclusion, we identified 13 novel genes differentially expressed in MPM, never reported before. Among them, BBS1 emerged as a novel predictor of overall survival in MPM. Finally, we identified that PARK7 interactome is involved in novel pathways pertinent in MPM disease. PMID:26254420

  12. Prognostic factors for hepatocellular carcinoma recurrence

    PubMed Central

    Colecchia, Antonio; Schiumerini, Ramona; Cucchetti, Alessandro; Cescon, Matteo; Taddia, Martina; Marasco, Giovanni; Festi, Davide

    2014-01-01

    The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor. PMID:24876717

  13. Gallbladder carcinoma: Prognostic factors and therapeutic options

    PubMed Central

    Goetze, Thorsten Oliver

    2015-01-01

    The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma’’ (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2

  14. KiSS-1 expression in oral squamous cell carcinoma and its prognostic significance.

    PubMed

    Shin, Wui-Jung; Cho, Young-Ah; Kang, Kyung-Rim; Kim, Ji-Hoon; Hong, Seong-Doo; Lee, Jae-Il; Hong, Sam-Pyo; Yoon, Hye-Jung

    2016-04-01

    Downregulated expression of KiSS-1 has been correlated with tumor progression, metastasis, and patient prognosis in various human malignancies. However, there is no information regarding the expression of KiSS-1 in oral squamous cell carcinoma (OSCC). Our aims were to examine KiSS-1 expression in OSCC tissue samples and cell lines and to determine its prognostic significance. KiSS-1 expression was significantly lower in lymph node (LN) metastases than in primary tumor tissues. Five of six OSCC cell lines showed absence or relatively low expression of KiSS-1. Correlations between KiSS-1 expression and clinicopathological parameters were statistically assessed. There were significant correlations between KiSS-1 expression and LN metastasis (p = 0.007), TNM stage (p = 0.024), and local recurrence (p = 0.012). In the Kaplan-Meier survival analysis, negative KiSS-1 expression significantly correlated with poorer overall survival (OS) and disease-free survival (DFS) (p = 0.000 and 0.000, respectively). Multivariate analysis using Cox regression modeling revealed that KiSS-1 expression was an independent prognostic factor for both OS and DFS (p = 0.001 and 0.000, respectively). Our findings suggested that KiSS-1 downregulation may play a role in tumor progression and metastasis of OSCC and may be a reliable biomarker for predicting clinical outcome in OSCC. PMID:26809635

  15. Multivariate analysis of prognostic factors in early stage Hodgkin's disease

    SciTech Connect

    Tubiana, M.; Henry-Amar, M.; van der Werf-Messing, B.; Henry, J.; Abbatucci, J.; Burgers, M.; Hayat, M.; Somers, R.; Laugier, A.; Carde, P.

    1985-01-01

    A multivariate analysis of the prognostic factors was carried out with a Cox model on 1,139 patients with clinical Stage I + II Hodgkin's disease included in three controlled clinical trials. The following indicators had been prospectively registered: aged, sex, systemic symptoms, erythrocyte sedimentation, results of staging laparotomy when performed, as well as the date and type of treatment. A linear logistic analysis showed that most of the indicators are interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The two main prognostic indicators for relapse-free survival are systemic symptoms and/or ESR and number of involved areas. The only significant factor for survival after relapse is age. Sex has a small but significant influence on relapse-free survival. The relative influence of each indicator varies with the type of treatment and these variations may help in understanding the biologic significance of the indicators.

  16. Prognostic value of SATB2 expression in patients with esophageal squamous cell carcinoma.

    PubMed

    Geng, Guo-Jun; Li, Ning; Mi, Yan-Jun; Yu, Xiu-Yi; Luo, Xian-Yang; Gao, Jing; Luo, Qi-Cong; Xie, Jing-Dun; Fa, Xian-En; Jiang, Jie

    2015-01-01

    SATB2, a member of the family of special AT-rich binding proteins, has been shown to affect numerous tumorigenesis. However, the role of SATB2 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, the SATB2 expression was examined at mRNA and protein levels by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry in ESCC tissues and adjacent non-cancerous tissues. Statistical analyses were applied to test the associations between SATB2 expression, clinicopathologic factors, and prognosis. Western blotting and qRT-PCR showed that the expression levels of SATB2 mRNA and protein were both significantly lower in SATB2 tissues than those in non-cancerous tissues. Immunohistochemistry analysis showed that SATB2 expression was significantly correlated with clinical stage and Histological differentiation. The results of Kaplan-Meier analysis indicated that a low expression level of SATB2 resulted in a significantly poor prognosis of ESCC patients. Importantly, multivariate analysis showed that low SATB2 expression was an independent prognostic factor for ESCC patients. In sum, our data suggest that SATB2 plays an important role in ESCC progression, and that decreased expression of SATB2 in tumor tissues could be used as a potential prognostic marker for patients with ESCC. PMID:25755730

  17. Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability.

    PubMed

    Sessa, Fausto; Furlan, Daniela; Zampatti, Clementina; Carnevali, Ileana; Franzi, Francesca; Capella, Carlo

    2007-09-01

    Prognostic factors for ampullary carcinomas (ACs) are poorly defined. Fifty three resected ACs were analyzed for CDX2, MUC1, MUC5AC, MUC6, MUC2, and for mismatch repair proteins (hMLH1, hMSH2, PMS2, hMSH6) using immunohistochemistry. Microsatellite instability (MSI) status was evaluated by fluorescently labeled PCR using an automated sequencer. Univariate and multivariate analysis was performed for clinicopathological, immunohistochemical and molecular parameters. CDX2 was found in 32 out of 53 (60%) ACs with a significantly higher frequency among intestinal ACs compared with biliopancreatic (BP) ACs. The MUC1, MUC5AC, MUC6, MUC2 apomucins were expressed in 75, 43, 39, and 28% of ACs, respectively, with a significantly higher coexpression of MUC1/MUC5AC in BP ACs. MSI and loss of expression of hMLH1/PMS2 or hMSH2/hMSH6 proteins were observed only in intestinal ACs. Factors significantly correlated with improved survival in the univariate analysis were: low stage, absence of lymph nodes metastases, negative surgical margins (R0 status), and presence of MSI. In the multivariate analysis, stage was the only independent prognostic factor of survival. We conclude that stage is the only independent prognostic factor of survival in the multivariate analysis, whereas histological criteria and the immunohistochemical expression of apomucins and CDX2 are helpful in the classification and understanding of the histogenesis of ACs. PMID:17653761

  18. Prognostic factors of hepatocellular carcinoma patients treated by transarterial chemoembolization.

    PubMed

    Xiao, Jun; Li, Guojian; Lin, Shuhan; He, Ke; Lai, Hao; Mo, Xianwei; Chen, Jiansi; Lin, Yuan

    2014-01-01

    We aim to investigate the clinical characteristics and prognostic factors of Hepatocellular Carcinoma (HCC) patients treated by transarterial chemoembolization (TACE) in Chinese cohort. A total of 2,493 HCC patients treated by TACE were included in this retrospective study. Patients were divided into the younger group (n=1,877) or the elderly group (n=616) based upon their ages (cut-off value of 60 y/o). Chi-square test or Wilcoxon rank-sum test was used to compare patients' characteristics. Univariate and multivariate analysis were used to determine prognostic factors. When compared with the younger group, the elderly group had lower male/female ratio and family liver disease history ratio, as well as advanced stage or Child-Pugh grade B patients. The median survival time was 8 months and 27 months for the younger and the elderly group, respectively. The 1-, 2-, and 3-year survival rates in the younger group and the elderly group were 31.82%, 12.5%, 6.53%, and 84.66%, 53.28%, 28.39%, respectively. Multivariate analysis showed that HBV infection, AFP value, TNM stage, Child-Pugh class, portal vein tumor thrombus (PVTT) and tumor number were independent prognostic factors for the younger patients; the elderly ones had similar independent prognostic factors except for HBV infection. The elderly group had lower male/female ratio and family history ratio, as well as advanced stage or Child-Pugh grade B patients. The elderly seems to have better prognosis than the younger ones, which is probably related to the fact that the elderly have lower tumor burden and better liver function. PMID:24696728

  19. Anatomical prognostic factors after abdominal perineal resection

    SciTech Connect

    Walz, B.J.; Green, M.R.; Lindstrom, E.R.; Butcher, H.R. Jr.

    1981-04-01

    The natural history of 153 patients with rectosigmoid adenocarcinoma treated by abdominal perineal resection was retrospectively studied with emphasis on survival, clinical signs and symptoms of recurrence distantly and in the pelvis. We analyzed diagnostic factors that might predict tumor stage preoperatively and anatomical factors of the tumor itself that might predict behaviour of the lesion. Age, sex, tumor size, and distance from the anal verge were not useful in predicting stage. Constriction of the lesion tended to occur with high stage, but was not a reliable predictor. The grade or differentiation of the biopsy (when noted) did not correlate with either the grade of the resected specimen or the stage. The highest grade of the resected specimen was quite predictive of subsequent outcome. Seventy-three percent of the poorly differentiated tumors were Stage C or D, though a lower grade specimen did not rule out high stage. The Astler-Coller stage was reliable in predicting the likelihood of survival, pelvic recurrence, and distant metastases. In Stage C patients, the number of positive lymph node metastases strongly affected prognosis: if only one node was positive, survival was intermediate between Stages B and C; if more than seven nodes were positive, no patient survived. Of the evaluable cases, 48% survived clinically free of disease five or more years; 43% failed (died of the rectosigmoid tumor); 22% developed pelvic recurrence (6% pelvis only, 16% pelvis plus distant metastases). Fifty-two percent of the patients failing had tumor in the pelvis. Seven of the 56 failures (13%) occurred at or after five years; six of these seven failed locally, usually with metastases. Patients under age 40 or over age 80 and the same results as the group in general. Sixteen percent of the entire group had major complications, 52% minor. There were eight postoperative deaths (5%); 18 patients (12%) required reoperation.

  20. [Prognostic and predictive factors in epithelial ovarian cancer].

    PubMed

    Boudou-Rouquette, P; Pautier, P; Morice, P; Lhommé, C

    2009-04-01

    Even if prognosis of epithelial ovarian cancer remains very bad, survival and response to treatment are variable according to the patients. Determination of new prognostic markers helps us to adapt therapeutics for each patient and is necessary for the elaboration and the interpretation of clinical research studies. Many prognostic factors related to the tumor, the patient or the treatment, have been evaluated. The goal of this work is to review these parameters. So far, the most powerful variables are volume of residual disease after cytoreductive surgery, FIGO tumor stage, histologic type and grade of differentiation. The progress and accessibility to novel technologies applied to biology will make possible in the future the assessment of new prognostic profiles-based on genetic and/or proteomic tumor characteristics. The future also relies on the identification of predictive factors of response to treatment, but force is to note that on the last hundred publications testing predictive factors (p53, HER2, Topo-2-alpha, BRCA...), none have modified today our clinical practices. PMID:19357017

  1. Expression and prognostic significance of unique ULBPs in pancreatic cancer

    PubMed Central

    Chen, Jiong; Zhu, Xing-Xing; Xu, Hong; Fang, Heng-Zhong; Zhao, Jin-Qian

    2016-01-01

    Background Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers. Materials and methods Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs. Results Statistics showed that high expression of membrane ULBP1 was a good biomarker of overall survival (18 months vs 13 months), and a high level of soluble ULBP2 was deemed an independent poor indicator for both overall survival (P<0.001) and disease-free survival (P<0.001). Conclusion ULBP1 provides additional information for early diagnosis, and soluble ULBP2 can be used as a novel tumor marker to evaluate the risk of pancreatic cancer patients. PMID:27621649

  2. Prognostic factors in extensive mesenteric ischaemia.

    PubMed Central

    Gorey, T. F.; O'Sullivan, M.

    1988-01-01

    The records of 65 patients with diagnoses of extensive intestinal ischaemia during the 10 years from December 1973 to January 1984 were retrieved from 18 hospitals in Ireland. There were 32 males and 33 females, ranging in age from 20 to 96 years (mean 69.8 years). Duration of symptoms ranged from 4 h to 8 days. Pain was the most common presenting feature. Gastrointestinal haemorrhage was apparent in 31%, hypotension in 28% and atrial fibrillation in 43%. Associated vascular disease was present in 43%. There were elevations of serum inorganic phosphate in 15%, leucoytosis in 65% and metabolic acidosis in 67%. The mean interval from hospital admission to operation in survivors was 14.5 h, whereas the mean delay in those who died was 44 h. The correct preoperative diagnosis was made in 23 (35%) and the aetiology of intestinal ischaemia was recorded as: thrombosis 25 (39%), embolism 12 (18%), adhesions/volvulus 4 (6%) and indeterminate in 24 (37%). Laparotomy was performed in 49: gangrenous bowel was resected in 29 and six had operations designed to revascularise the intestine. The remaining 14 patients either had laparotomy alone (12) or an inappropriate operation (2). In 46 patients (70.8%) who died, death was related to three factors: the mean age of survivors was 7 years less than that of patients who died, the interval to laparotomy was on average 30 h less, and the length of ischaemic bowel was on average 61% less. PMID:3415165

  3. Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer

    PubMed Central

    Fan, Yi; Xu, Zhe; Fan, Jin; Huang, Liu; Ye, Ming; Shi, Kun; Huang, Zheng; Liu, Yaqiong; He, Langchi; Huang, Jiezhen; Wang, Yibin; Li, Qiufeng

    2016-01-01

    Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed that DDR2 mRNA expression was upregulated in ovarian cancer tissues compared with normal ovary tissues. Statistical analysis revealed that DDR2 expression correlated with tumor stage (P = 0.008) and peritoneal metastasis (P = 0.009). Patients with high DDR2 expression showed poorer 5-year overall survival (P = 0.005), and DDR2 remained an independent prognostic marker for OS (P = 0.013) in multivariate analysis. Our results suggest that DDR2 might be closely associated with ovarian cancer progression and metastasis. Its high expression may serve as a potential prognostic biomarker in human ovarian cancer. PMID:27398168

  4. The prognostic significance of fibroblast growth factor receptor 4 in non-small-cell lung cancer

    PubMed Central

    Huang, Hong-ping; Feng, Hui; Qiao, Hong-bo; Ren, Ze-xiang; Zhu, Ge-dong

    2015-01-01

    Background Fibroblast growth factor receptor 4 (FGFR4) has been proved to be correlated with progression and prognosis in many cancers. However, the significance of FGFR4 in non-small-cell lung cancer (NSCLC) is still not well elucidated. Methods In our experiment, we detected FGFR4 expression in 237 samples of NSCLC with immunohistochemistry, and further analyzed the correlation between FGFR4 and clinicopathologic features of NSCLC with chi-square test. Moreover, we evaluated the prognostic value of FGFR4 by Kaplan–Meier survival curve and Cox regression model. By regulating the expression of FGFR4 by overexpression or knockdown, we assessed the role of FGFR4 on NSCLC cell proliferation. Results FGFR4 expression was high in NSCLC (46.8%, 111/237). FGFR4 expression was significantly associated with tumor diameter (P=0.039). With univariate (P=0.009) and multivariate (P=0.002) analysis, FGFR4 was identified as an independent prognostic factor in NSCLC (P=0.009). Moreover, FGFR4 can promote the proliferation of NSCLC cell lines. Conclusion FGFR4 is an independent prognostic biomarker in NSCLC. FGFR4 can accelerate the proliferation of NSCLC cell lines, indicating FGFR4 could be a potential drug target of NSCLC. PMID:26045670

  5. Prognostic implications of expression of the cell cycle inhibitor protein p27Kip1.

    PubMed

    Cariou, S; Catzavelos, C; Slingerland, J M

    1998-01-01

    Mitogenic and growth inhibitory signals influence the activity of a family of cyclin dependent kinases (cdks). p27 is an important cdk inhibitor, acting in G1 to inhibit cyclin-cdks. As negative growth regulators, the cdk inhibitors may function as tumor suppressors. While the p16 gene plays a tumor suppressor role in cancers, p27 gene mutations have been identified only rarely. While high levels of p27 protein are expressed in normal human mammary epithelium, loss of p27 is frequent and is of independent prognostic significance in breast cancers. Low p27 is also a poor prognostic factor in colon, gastric, esophageal, lung, and prostate carcinomas, and enhanced proteasomal degradation may underlie loss of p27 in tumor cells. Loss of p27 has not been significantly correlated with tumor proliferation in a number of studies and may reflect alterations in differentiation and adhesion-dependent growth regulation germane to oncogenesis and tumor progression. Efforts to confirm the prognostic value of p27 are under way in a number of large breast cancer studies. These studies may also indicate whether loss of p27 in association with other traditional or novel markers has greater prognostic potential than each factor alone. p27 immunostaining is inexpensive and reliable and may become part of the routine histopathologic processing of tumors in the near future. Widespread application of p27 in prognostic testing will require greater uniformity in scoring techniques and determination of the cut off levels which distinguish individuals at high and low risk of cancer recurrence and death. Finally, the greatest utility of p27 may lie in the information it sheds on the biology of aberrant growth regulation in breast cancer and the potential to use this in the generation of novel therapeutic strategies. PMID:10066070

  6. Wilms' tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT.

    PubMed

    Zhao, X-S; Jin, S; Zhu, H-H; Xu, L-P; Liu, D-H; Chen, H; Liu, K-Y; Huang, X-J

    2012-04-01

    To evaluate the prognostic significance of Wilms' tumor gene 1 (WT1) expression for monitoring minimal residual disease and predicting relapse in patients with acute leukemia (AL) following allogeneic hematopoietic SCT (allo-HSCT), the WT1 expression levels of 138 AL patients were measured using real-time quantitative reverse transcription PCR at designed time points after allo-HSCT. All patients were divided into four groups based on the HSCT outcomes and intervention application. A low level of WT1 expression following HSCT indicated a low risk of relapse, whereas WT1 expression >1.05% was indicative of a higher probability of relapse. Only the advanced stage of disease (hazard ratio (HR)=2.73; 95% confidence interval (CI)=1.337-5.573, P=0.006) and a WT1 expression ≥ 0.60% (HR=4.774; 95% CI=2.410-9.459, P=0.000) were associated with lower disease-free survival. Relapse (HR=0.119; 95% CI=0.056-0.250, P=0.000) and a WT1 expression 0.60% (HR=2.771; 95% CI=1.316-5.834, P=0.007) were associated with lower OS. In conclusion, the WT1 expression level is an independent prognostic factor that can predict clinical outcomes for AL patients after HSCT and provide a guide for suitable interventions. PMID:21643023

  7. Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Hagag, Adel A; Badraia, Ibrahim M; Hassan, Samir M; Abd El-Lateef, Amal E

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. Aim of the work The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL. Patients and methods This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, thorough clinical examination and laboratory investigations including; complete blood count, LDH, BM aspiration, cytochemistry, immunophenotyping, FISH technique for detection of t(12;21) and t(9;22) and assessment of WT-1 Gene by real-time PCR in BM samples at time of diagnosis. Results Positive WT-1 gene expression was found in 22 cases (55%) and negative expression in 18 cases (45%). Positive WT-1 gene expression group (n=22) includes 14 males and 8 females with mean age at presentation of 5.261 ± 0.811 while negative WT-1 gene expression group (n=18) includes 12 males and 6 females with mean age at diagnosis of 9.669 ± 3.731 with significantly older age in negative WT-1 gene expression group but no significant differences between positive and negative WT-1 gene expression groups regarding sex and clinical presentations. There were no significant differences in platelets and WBCs counts, hemoglobin and LDH levels and the number of peripheral blood and BM blast cells at diagnosis between positive and negative WT-1 gene expression groups but after induction therapy there were significantly lower BM blast cells in positive WT-1 gene expression group. There were no statistically significant differences between positive and negative WT-1 gene expression groups regarding immunophenotyping and chromosomal translocations including t(12;21) and t(9;22). There were a significantly higher relapse and death rate and a lower rate of CR, DFS, and OAS in negative WT-1 gene expression

  8. Lack of prognostic significance of adiponectin immunohistochemical expression in patients with triple-negative breast cancer

    PubMed Central

    Olmez, Omer Fatih; Kanat, Ozkan; Kabul, Selva; Canhoroz, Mustafa; Avci, Nilufer; Hartavi, Mustafa; Deligonul, Adem; Çubukçu, Sinem; Manavoglu, Osman

    2014-01-01

    Introduction Triple-negative breast cancers (TNBCs) – which lack the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) – have no established markers that can be used for prognostic stratification. As adiponectin has been previously implicated in a more aggressive phenotype of primary breast cancer, we explored the relation between adiponectin immunohistochemical expression and prognosis in TNBCs. Material and methods Immunohistochemical staining for adiponectin was performed in 38 TNBC patients. Disease-free survival (DFS) and overall survival (OS) served as the main outcome measures. Results Of the 38 TNBC patients, 18 (47%) had negative and 20 (53%) positive adiponectin immunohistochemical expression. We did not find any significant association between adiponectin immunohistochemical expression and the baseline characteristics. In addition, there were no associations between adiponectin immunohistochemical expression and prognosis. Conclusions Although our results suggest that adiponectin immunohistochemical expression is not of prognostic significance in TNBCs, further studies are warranted to determine the role of this adipokine in breast cancer biology. PMID:24876819

  9. Prognostic Factors for Visual Outcome in Traumatic Cataract Patients

    PubMed Central

    Zhang, Yan F.; Zhu, Yu; Wan, Ming G.; Du, Shan S.; Yue, Zhen Z.

    2016-01-01

    Purpose. To investigate the prognostic factors for visual outcome in traumatic cataract patients. Methods. The demographic features of traumatic cataract patients in Central China were studied. The factors that might influence the visual outcome were analyzed. The sensitivity and specificity of OTS (ocular trauma score) in predicting VA were calculated. Results. The study enrolled 480 cases. 65.5% of patients achieved VA at >20/60. The factors associated with the final VA were initial VA, injury type, wound location, the way of cataract removal, and IOL implantation. The sensitivities of OTS in predicting the VA at NLP (nonlight perception), LP/HM (light perception/hand motion), and ≥20/40 were 100%. The specificity of OTS to predict the final VA at 1/200-19/200 and 20/200-20/50 was 100%. Conclusion. The prognostic factors were initial VA, injury type, wound location, cataract removal procedure, and the way of IOL implantation. The OTS has good sensitivity and specificity in predicting visual outcome in traumatic cataract patients in long follow-up. PMID:27595014

  10. Prognostic Factors for Visual Outcome in Traumatic Cataract Patients.

    PubMed

    Qi, Ying; Zhang, Yan F; Zhu, Yu; Wan, Ming G; Du, Shan S; Yue, Zhen Z

    2016-01-01

    Purpose. To investigate the prognostic factors for visual outcome in traumatic cataract patients. Methods. The demographic features of traumatic cataract patients in Central China were studied. The factors that might influence the visual outcome were analyzed. The sensitivity and specificity of OTS (ocular trauma score) in predicting VA were calculated. Results. The study enrolled 480 cases. 65.5% of patients achieved VA at >20/60. The factors associated with the final VA were initial VA, injury type, wound location, the way of cataract removal, and IOL implantation. The sensitivities of OTS in predicting the VA at NLP (nonlight perception), LP/HM (light perception/hand motion), and ≥20/40 were 100%. The specificity of OTS to predict the final VA at 1/200-19/200 and 20/200-20/50 was 100%. Conclusion. The prognostic factors were initial VA, injury type, wound location, cataract removal procedure, and the way of IOL implantation. The OTS has good sensitivity and specificity in predicting visual outcome in traumatic cataract patients in long follow-up. PMID:27595014

  11. Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer

    PubMed Central

    2012-01-01

    -catenin overexpression, microsatellite stability and SATB2 expression. Furthermore, SATB1 expression is a factor of poor prognosis in SATB2 negative tumours. Altogether, these data indicate an important role for SATB1 in colorectal carcinogenesis and suggest prognostically antagonistic effects of SATB1 and SATB2. The mechanistic basis for these observations warrants further study. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1922643082772076 PMID:22935204

  12. Identification of prognostic biomarkers for glioblastomas using protein expression profiling

    PubMed Central

    JUNG, YONG; JOO, KYEUNG MIN; SEONG, DONG HO; CHOI, YOON-LA; KONG, DOO-SIK; KIM, YONGHYUN; KIM, MI HYUN; JIN, JUYOUN; SUH, YEON-LIM; SEOL, HO JUN; SHIN, CHUL SOO; LEE, JUNG-IL; KIM, JONG-HYUN; SONG, SANG YONG; NAM, DO-HYUN

    2012-01-01

    A set of proteins reflecting the prognosis of patients have clinical significance since they could be utilized as predictive biomarkers and/or potential therapeutic targets. With the aim of finding novel diagnostic and prognostic markers for glioblastoma (GBM), a tissue microarray (TMA) library consisting of 62 GBMs and 28 GBM-associated normal spots was constructed. Immunohistochemistry against 78 GBM-associated proteins was performed. Expression levels of each protein for each patient were analyzed using an image analysis program and converted to H-score [summation of the intensity grade of staining (0–3) multiplied by the percentage of positive cells corresponding to each grade]. Based on H-score and hierarchical clustering methods, we divided the GBMs into two groups (n=19 and 37) that had significantly different survival lengths (p<0.05). In the two groups, expression of nine proteins (survivin, cyclin E, DCC, TGF-β, CDC25B, histone H1, p-EGFR, p-VEGFR2/3, p16) was significantly changed (q<0.05). Prognosis-predicting potential of these proteins were validated with another independent library of 82 GBM TMAs and a public GBM DNA microarray dataset. In addition, we determined 32 aberrant or mislocalized subcellular protein expression patterns in GBMs compared with relatively normal brain tissues, which could be useful for diagnostic biomarkers of GBM. We therefore suggest that these proteins can be used as predictive biomarkers and/or potential therapeutic targets for GBM. PMID:22179774

  13. Prognostic factors on periapical surgery: A systematic review

    PubMed Central

    Serrano-Giménez, Mireia; Sánchez-Torres, Alba

    2015-01-01

    Background Analyze the most important prognostic factors when performing periapical surgery and compare the success rates of distinct authors. Introduction Periapical surgery is an approach to treat non-healing periapical lesions and it should be viewed as an extension of endodontic treatment and not as a separate entity. Material and Methods A search of articles published in Cochrane, PubMed (MEDLINE) and Scopus was conducted with the key words “prognostic factors”, “prognosis”, “periapical surgery”, “endodontic surgery” and “surgical endodontic treatment”. The inclusion criteria were articles including at least 10 patients, published in English, for the last 10 years. The exclusion criteria were nonhuman studies and case reports. Results 33 articles were selected from 321 initially found. Ten articles from 33 were excluded and finally the systematic review included 23 articles: 1 metaanalysis, 1 systematic review, 2 randomized clinical trials, 6 reviews, 12 prospective studies and 1 retrospective study. They were stratified according to their level of scientific evidence using the SORT criteria. Conclusions Factors associated with a better outcome of periapical surgery are patients ≤45 years old, upper anterior or premolar teeth, ≤10 sized lesions, non cystic lesions, absence of preoperative signs and symptoms, lesions without periodontal involvement, teeth with an adequate root-filling length, MTA as root-end filling material, uniradicular teeth, absence of perforating lesions, apical resection < 3 mm, teeth not associated to an oroantral fistula and teeth with only one periapical surgery. Key words:Prognostic factors, prognosis, periapical surgery, endodontic surgery and surgical endodontic treatment. PMID:26449431

  14. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.

    PubMed

    Voorwinden, Jan S; Jaspers, Jan P C

    2016-06-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network. PMID:26475052

  15. Prognostic factors for stereopsis in refractive accommodative esotropia

    PubMed Central

    Guclu, Hande; Gurlu, Vuslat Pelitli; Ozal, Sadik Altan; Ozkurt, Zeynep Gursel

    2015-01-01

    Objective: To determine the prognostic factors affecting stereoacuity in patients with refractive accommodative esotropia (RAE) according to the results of long follow- up period. Methods: We reviewed the charts of 70 patients with RAE between the years 1985-2014. Patients were classified into three groups. G-1: Stereoacuity score 40 second/arc. G-2: Stereoacuity score >40 second/arc (50-3000). G-3: No binocular vision. Initiation age of RAE, duration of deviation, refractive error, amblyopia, amblyopia treatment, anisometropia, visual acuity, family history, angle of deviation for distance and near at each group and the prognostic factors affecting stereoacuity were analyzed. Results: The mean initiation age of RAE was 2.7±1.5 years, the mean age at first visit was 6.4±4.2 years. The mean follow up time was 7.3±4.4 years. Seven patients had 40 second/arc, 48 patients had 50 to 3000 second/arc stereoacuity, 15 patients had no binocular vision. Mean deviation for near was statistically higher in group 2 and 3. Visual acuity levels were higher in group 1 and 2 and was statistically significant. Low visual acuity (p=0.001, 0.008), higher angle of deviation at near (p=0.01), increased duration of deviation (p=0.01), presence of amblyopia (p=0.001) and irregularity of amblyopia treatment (p=0.01) were significantly related with poor stereoacuity. Conclusion: According to the prognostic factors low stereoacuity was mostly related with amblyopia as a result the late presentation of the patients in seeking care. Appropriate treatment as full refractive correction and amblyopia treatment during the RAE is important for development of good stereopsis. Also angle of deviation at near and duration of deviation can be a useful predictor for poor stereoacuity levels. PMID:26430408

  16. LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia

    PubMed Central

    Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

    2011-01-01

    Background The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Design and Methods Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. Results High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. Conclusions LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis. PMID:21508119

  17. Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors.

    PubMed

    Rusakiewicz, Sylvie; Semeraro, Michaela; Sarabi, Matthieu; Desbois, Mélanie; Locher, Clara; Mendez, Rosa; Vimond, Nadège; Concha, Angel; Garrido, Federico; Isambert, Nicolas; Chaigneau, Loic; Le Brun-Ly, Valérie; Dubreuil, Patrice; Cremer, Isabelle; Caignard, Anne; Poirier-Colame, Vichnou; Chaba, Kariman; Flament, Caroline; Halama, Niels; Jäger, Dirk; Eggermont, Alexander; Bonvalot, Sylvie; Commo, Frédéric; Terrier, Philippe; Opolon, Paule; Emile, Jean-François; Coindre, Jean-Michel; Kroemer, Guido; Chaput, Nathalie; Le Cesne, Axel; Blay, Jean-Yves; Zitvogel, Laurence

    2013-06-15

    Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8(+) T cells with a T-helper cell 1 (TH1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes (TIL) expressing CD3, Foxp3, or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3(+) TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment. High densities of CD3(+) TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokine-secreting CD56(bright) (NCAM1) NK cells that accumulated in tumor foci after imatinib mesylate treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST. PMID:23592754

  18. [Determination of prognostic factors in surgical treatment of myasthenia gravis].

    PubMed

    Schnorrer, M; Hraska, V; Spalek, P; Cársky, S

    1999-05-01

    The authors evaluated, using statistical analysis, the importance of prognostic factors in patients subjected to thymectomy on account of myasthenia gravis. The results revealed a better prognosis of the disease, if the history was less than 6 months, preoperative treatment less than 1.5 years, a histological finding of thymus hyperplasia, second clinical stage according to Ossermann and the patients age below 30 years. From the statistical analysis ensues that the prognosis of myasthenia gravis is more favourable when the case-history is shorter as a result of rapid diagnosis and when preoperative treatment is reduced to a minimum. PMID:10510623

  19. The prognostic role and reduced expression of FOXJ2 in human hepatocellular carcinoma

    PubMed Central

    ZHANG, ZHONGBAO; MENG, GUANGJU; WANG, LIANG; MA, YINGYING; GUAN, ZHONGZHENG

    2016-01-01

    The current study aimed to investigate the potential role of the FOXJ2 (forkhead box J2) protein in the pathology of hepatocellular carcinoma (HCC). Western blotting was performed to determine the expression levels of FOXJ2 in HCC tissues and HCC cells. Specimens from 110 patients with HCC undergoing hepatic resection were evaluated for FOXJ2 expression using an immunohistochemical assay. The correlation between FOXJ2 expression and clinicopathological factors of the patients was determined by statistical analysis to determine the prognostic merit of FOXJ2 expression in HCC. The detailed involvement of FOXJ2 in the regulation of HCC proliferation was further investigated using FOXJ2-targeting small interfering RNA (siRNA). FOXJ2 protein was identified to be significantly downregulated in HCC tissues compared with adjacent normal liver tissues. Immunohistochemical analysis demonstrated that the expression of FOXJ2 was negatively correlated with Ki-67 levels in HCC specimens (r=−0.679, P<0.001). Furthermore, statistical analysis indicated FOXJ2 expression was significantly associated with histological differentiation (P=0.005), the size of largest tumor (P=0.002) and metastasis (P=0.036). Using Kaplan-Meier analysis, it was demonstrated that high FOXJ2 expression levels predicted significantly improved patient survival rates compared with low FOXJ2 expression levels (P<0.001). In addition, it was observed that interference of FOXJ2 expression using siRNA oligos led to the promotion of proliferation of HepG2 cells. FOXJ2 was markedly downregulated in HCC tissues. The expression of FOXJ2 was correlated with tumor size, histological differentiation and metastasis. Low expression levels of FOXJ2 predicted poor prognosis for patients with HCC, suggesting that FOXJ2 may be a candidate prognostic marker of HCC. Depletion of FOXJ2 caused the promotion of HCC cell proliferation, implicating that FOXJ2 may serve an inhibitory role in the regulation of HCC cell proliferation

  20. Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

    PubMed Central

    2014-01-01

    Background New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients. Methods MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade. Results Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes. Conclusions Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility. PMID:25015560

  1. Surgical outcome and prognostic factors in patients with gallbladder carcinoma

    PubMed Central

    Hong, Eun Kyung; Kim, Kun Kuk; Lee, Jung Nam; Lee, Woon Kee; Chung, Min; Kim, Yeon Suk

    2014-01-01

    Backgrounds/Aims Gallbladder carcinoma is usually associated with an unfavorable prognosis, and the clinical outcome has not improved much. This study was conducted to evaluate outcomes with gallbladder carcinoma according to the type of surgery performed, and the prognostic factors for survival. Methods One hundred and six patients with gallbladder carcinoma, who underwent surgery for the purpose of curative resection between January 1999 and June 2012 were reviewed retrospectively. Results Out of 106 patients, curative resection was achieved in 75 (70.8%). The cumulative 1-, 2- and 5-year survival rates of the gallbladder carcinoma patients were 93.4%, 80.9% and 63.0%, respectively. Radical resections, including extended cholecystectomy, were more beneficial for long term survival of patients. The 5-year survival rate in patients who underwent curative resection (56.9%) was significantly higher than in those who underwent palliative resection (0%, p=0.000). Multivariate analysis revealed that curative resection, preoperative CA19-9, T-stage, N-stage and differentiation of histology were independently significant prognostic factors. Conclusions Curative resection and early detection of patients with gallbladder carcinoma were the most important factors for long term survival. Radical resection improves survival for patients with localized gallbladder carcinoma and can help to access exact prognosis and treatments. PMID:26155265

  2. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients.

    PubMed

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke; Trapman-Jansen, Anita M A C; Foekens, Renée; Look, Maxime P; Smid, Marcel; van Deurzen, Carolien H M; Span, Paul N; Sweep, Fred C G J; Brask, Julie Benedicte; Timmermans-Wielenga, Vera; Foekens, John A; Martens, John W M; Umar, Arzu

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules. PMID:27558661

  3. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

    PubMed Central

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke; Trapman-Jansen, Anita M. A. C.; Foekens, Renée; Look, Maxime P.; Smid, Marcel; van Deurzen, Carolien H. M.; Span, Paul N.; Sweep, Fred C. G. J.; Brask, Julie Benedicte; Timmermans-Wielenga, Vera; Foekens, John A.; Martens, John W. M.; Umar, Arzu

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules. PMID:27558661

  4. Prognostic factors in early-stage ovarian cancer.

    PubMed

    Tognon, Germana; Carnazza, Mario; Ragnoli, Monica; Calza, Stefano; Ferrari, Federico; Gambino, Angela; Zizioli, Valentina; Notaro, Sara; Sostegni, Benedetta; Sartori, Enrico

    2013-01-01

    The purpose of this study was to identify the main prognostic factors in patients with early-stage epithelial ovarian cancer. Data were extracted from 222 patients with initial stage (I-IIA) invasive epithelial ovarian cancer treated with primary surgery followed or not followed by adjuvant therapy, from 1 January 1980 to 31 December 2008, at the Division of Obstetrics and Gynecology, Spedali Civili, Brescia, Italy; the median follow-up was 79 months (SD ± 35,945, range 20-250 months). The negative prognostic factors that were statistically significant (p<0.050) in univariate analysis were grade 2, 3, and X (clear cell in our study); stage IB, IC, IIA; positive peritoneal cytology, age equal to/greater than 54; dense adhesions; capsule rupture (pre-operative or intra-operative) and endometrioid histotype (only for disease-free survival (DFS)). Positive cytology was strongly associated with peritoneal relapses, while adhesions were associated with pelvic relapses. A positive prognosis was associated with the mucinous histotype. Conservative treatment had been carried out in 52% of patients under 40 years of age, and we detected only two relapses and three completions of surgery after a few weeks among 31 women in total. Our study indicated a possible execution in patients with patients with cancer stage IA G1-G2 (p=0.030) or IC G1 (p=0.050), provided well staged. Adjuvant chemotherapy improved the survival of cancers that were not IA G1. The positive prognostic role of taxanes must be emphasised, when used in combination with platino. PMID:23781280

  5. Prognostic factors of choroidal melanoma in Slovenia, 1986–2008

    PubMed Central

    Budihna, Marjan; Drnovsek-Olup, Brigita; Andrejcic, Katrina Novak; Zupancic, Irena Brovet; Pahor, Dusica

    2016-01-01

    Introduction Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. Patients and methods From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. Results Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. Conclusions It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation. PMID:27069456

  6. Short-term prognostic factors in lumbar disc surgery: the low back prognostic score is of predictive value.

    PubMed

    Woertgen, C; Gliese, M; Rothoerl, R D; Holzschuh, M; Schlaier, J; Ullrich, O W; Brawanski, A

    1998-01-01

    In order to determine prognostic factors of lumbar disc surgery, we examined 107 patients who were conventionally operated on in a prospective, consecutive study. We analysed general data, the case history, the neurological examination at admission and all data from imaging examinations and therapy. In addition, all patients received a questionnaire based on the Low Back Outcome Score [9, 10]. The patients were re-examined after 2-8 months (103 days mean). According to their ratings on a pain grading scale, the patients were divided into a group with favorable and another with unfavorable results. These groups were analysed in relation to the patients' initial condition. At follow up, 88% of the patients had either completely recovered or their complaints had been relieved. According to the Low Back Outcome Score (LBOS), 64.5% went well. Used to evaluate the initial condition of the patients on admission the LBOS was able to predict favorable outcome in 68% and unfavorable outcome in 50%. To improve the prognostic value, we combined significant questions of the LBOS with the pain grading scale and significant prognostic factors to form a new prognostic score (Low Back Prognostic Score). With this new score we were able to predict a favorable outcome in 84% of our patients, and an unfavorable outcome in 71%. The Low Back Prognostic score seems to provide a sensitive method for predicting a favorable or unfavorable outcome for patients scheduled to undergo lumbar disc surgery. PMID:9577926

  7. Prognostic Significance of Human Apurinic/Apyrimidinic Endonuclease (APE/Ref-1) Expression in Rectal Cancer Treated With Preoperative Radiochemotherapy

    SciTech Connect

    Kim, Jun-Sang; Kim, Jin-Man; Liang, Zhe Long; Jang, Ji Young; Kim, Sup; Huh, Gil Ja; Kim, Ki-Hwan; Cho, Moon-June

    2012-01-01

    Purpose: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+). Methods and Materials: APE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated. Results: APE/Ref-1 was expressed in 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046). Conclusions: APE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse

  8. Association of Telomere Length with Breast Cancer Prognostic Factors

    PubMed Central

    Têtu, Bernard; Maunsell, Elizabeth; Poirier, Brigitte; Montoni, Alicia; Rochette, Patrick J.; Diorio, Caroline

    2016-01-01

    Introduction Telomere length, a marker of cell aging, seems to be affected by the same factors thought to be associated with breast cancer prognosis. Objective To examine associations of peripheral blood cell-measured telomere length with traditional and potential prognostic factors in breast cancer patients. Methods We conducted a cross-sectional analysis of data collected before surgery from 162 breast cancer patients recruited consecutively between 01/2011 and 05/2012, at a breast cancer reference center. Data on the main lifestyle factors (smoking, alcohol consumption, physical activity) were collected using standardized questionnaires. Anthropometric factors were measured. Tumor biological characteristics were extracted from pathology reports. Telomere length was measured using a highly reproducible quantitative PCR method in peripheral white blood cells. Spearman partial rank-order correlations and multivariate general linear models were used to evaluate relationships between telomere length and prognostic factors. Results Telomere length was positively associated with total physical activity (rs = 0.17, P = 0.033; Ptrend = 0.069), occupational physical activity (rs = 0.15, P = 0.054; Ptrend = 0.054) and transportation-related physical activity (rs = 0.19, P = 0.019; P = 0.005). Among post-menopausal women, telomere length remained positively associated with total physical activity (rs = 0.27, P = 0.016; Ptrend = 0.054) and occupational physical activity (rs = 0.26, P = 0.021; Ptrend = 0.056) and was only associated with transportation-related physical activity among pre-menopausal women (rs = 0.27, P = 0.015; P = 0.004). No association was observed between telomere length and recreational or household activities, other lifestyle factors or traditional prognostic factors. Conclusions Telomeres are longer in more active breast cancer patients. Since white blood cells are involved in anticancer immune responses, these findings suggest that even regular low

  9. Intratumoral expression of cyclooxygenase-2 (COX-2) is a negative prognostic marker for patients with cutaneous melanoma.

    PubMed

    Kuźbicki, Łukasz; Lange, Dariusz; Stanek-Widera, Agata; Chwirot, Barbara W

    2016-10-01

    Because of the well-known heterogeneity of melanomas, prognosis of the disease is often difficult to assess even for lesions classified in similar stages. The aim of this study was to assess the usefulness of COX-2 as a melanoma prognostic marker and to establish an optimum algorithm for analysis of COX-2 expression levels in lesions of interest. Expression of COX-2 was detected immunohistochemically in standard sections of formalin-fixed paraffin-embedded tissue samples of 85 primary melanomas, 36 lymph node metastases, and five skin metastases including 39 cases of paired primary and metastatic lesions obtained from the same patient. Enhanced expression of COX-2 in primary melanomas is an indicator of poorer prognosis. A significant correlation was found between high expression of COX-2 in primary lesions and shorter survival. The enhancement of COX-2 expression is also positively correlated with other prognostic factors such as tumor thickness and infiltration level, ulceration, high mitotic index, more invasive histologic type, vertical growth phase, and lymph node metastasis. On the whole, the results suggest that intratumoral expression of COX-2 is a strong negative prognostic marker for patients with melanoma. Moreover, our work shows that a simple and objective immunohistochemical scoring algorithm involving the determination of only a percentage fraction of positively stained cells is sufficient to obtain the prognostic information. PMID:27391144

  10. Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma

    PubMed Central

    Walter, Scott D.; Chao, Daniel L.; Feuer, William; Schiffman, Joyce; Char, Devron H.; Harbour, J. William

    2016-01-01

    IMPORTANCE Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis. OBJECTIVE To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification. DESIGN, SETTING, AND PARTICIPANTS This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015. MAIN OUTCOME AND MEASURES Progression-free survival (PFS). The secondary outcome was overall survival. RESULTS The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30–24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02–1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04–1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at

  11. Pediatric non-Hodgkin's lymphoma: clinical and biologic prognostic factors and risk allocation.

    PubMed

    Weitzman, Sheila; Suryanarayan, Kaveri; Weinstein, Howard J

    2002-03-01

    The use of effective combination chemotherapy for all stages and subtypes of non-Hodgkin"s lymphoma (NHL) in children has resulted in a striking improvement in cure rates. Event-free survival now ranges from 70% to 90%, depending on the stage of disease and the NHL subtype. Risk-adapted therapy has resulted in a dramatic improvement in outcome for high-risk patients, at the cost of significantly increased short-term toxicity, and a reduction of therapy and toxicity for the lower-risk patient, while maintaining the excellent cure rate. Successful risk allocation of patients is dependent on the identification and continual validation of prognostic factors. The specific treatment protocol is the single most important factor predicting outcome today. Traditional prognostic factors such as stage and tumor burden are useful in selecting the intensity and length of therapy, rather than as a major indicator of likelihood of survival. In order to further improve cure rates and decrease toxicity, new biologic prognosticators need to be found and validated. Some promising avenues for study appear to be the presence or absence of adhesion molecules and of aberrant proteins that are specific to subtypes of lymphomas, such as soluble CD30 and anaplastic lymphoma kinase (ALK), the molecular classification of lymphomas on the basis of gene expression, and the evaluation of biologic markers for measuring early response to therapy. PMID:11822982

  12. Identification of prognostic factors in canine mammary malignant tumours: a multivariable survival study

    PubMed Central

    2013-01-01

    Background Although several histopathological and clinical features of canine mammary gland tumours have been widely studied from a prognostic standpoint, considerable variations in tumour individual biologic behaviour difficult the definition of accurate prognostic factors. It has been suggested that the malignant behaviour of tumours is the end result of several alterations in cellular physiology that culminate in tumour growth and spread. Accordingly, the aim of this study was to determine, using a multivariable model, the independent prognostic value of several immunohistochemically detected tumour-associated molecules, such as MMP-9 and uPA in stromal cells and Ki-67, TIMP-2 and VEGF in cancer cells. Results Eighty-five female dogs affected by spontaneous malignant mammary neoplasias were followed up for a 2-year post-operative period. In univariate analysis, tumour characteristics such as size, mode of growth, regional lymph node metastases, tumour cell MIB-1 LI and MMP-9 and uPA expressions in tumour-adjacent fibroblasts, were associated with both survival and disease-free intervals. Histological type and grade were related with overall survival while VEGF and TIMP-2 were not significantly associated with none of the outcome parameters. In multivariable analysis, only a MIB-1 labelling index higher than 40% and a stromal expression of MMP-9 higher than 50% retained significant relationships with poor overall and disease-free survival. Conclusions The results of this study indicate that MMP-9 and Ki-67 are independent prognostic markers of canine malignant mammary tumours. Furthermore, the high stromal expressions of uPA and MMP-9 in aggressive tumours suggest that these molecules are potential therapeutic targets in the post-operative treatment of canine mammary cancer. PMID:23289974

  13. Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer

    PubMed Central

    Zhang, Wei; He, Jian; Du, Yan; Gao, Xian-Hua; Liu, Yan; Liu, Qi-Zhi; Chang, Wen-Jun; Cao, Guang-Wen; Fu, Chuan-Gang

    2015-01-01

    AIM: To investigate the expression and oncogenic role of nemo-like kinase (NLK) in colorectal cancer. METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer. RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer (P < 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overall survival (hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P < 0.001) and disease-free survival (hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P < 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells. CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis. PMID:26269673

  14. Growth differentiation factor 15 is a promising diagnostic and prognostic biomarker in colorectal cancer.

    PubMed

    Li, Chen; Wang, Xiaobing; Casal, Ignacio; Wang, Jingyu; Li, Peiwei; Zhang, Wei; Xu, Enping; Lai, Maode; Zhang, Honghe

    2016-08-01

    Although various studies have demonstrated that growth differentiation factor 15 (GDF15) might be a potential diagnostic and prognostic marker in colorectal cancer (CRC) patients, the results are inconsistent and the statistical power of individual studies is also insufficient. An original study was conducted to explore the diagnostic and prognostic value of serum GDF15 in CRC patients. We also conducted a meta-analysis study which aimed to summarize the diagnostic and prognostic performance of serum GDF15 in CRC. We searched PubMed and ISI Web of Knowledge up to 1 November 2014 for eligible studies. In order to explore the diagnostic performance of GDF15, standardized mean difference (SMD) and their 95% confidence intervals (CI) were estimated and receiver-operating characteristic (ROC) curves were constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of serum GDF15 for survival were summarized. A total of eight studies were included in the meta-analyses. Our results revealed that serum GDF15 levels in CRC patients were higher than those in healthy controls (SMD = 1.08, 95% CI: 0.56-1.59, P < 0.001). For discriminating CRC from healthy controls, the AUC of GDF15 was 0.816 (95% CI: 0.792-0.838). The sensitivity and specificity were 58.9% (95% CI: 55.0-62.8) and 92.08% (95% CI: 89.2-94.4), respectively, when a cut-off value of 1099 pg/ml was established. Besides, higher GDF15 expression level was associated with worse overall survival for CRC patients (pooled HR = 2.09, 95% CI: 1.47-2.96). In conclusion, the present meta-analysis suggests that serum GDF15 may be a useful diagnostic and prognostic biomarker for CRC. PMID:26990020

  15. Leptomeningeal metastasis: survival and prognostic factors in 155 patients.

    PubMed

    Herrlinger, Ulrich; Förschler, Heike; Küker, Wilhelm; Meyermann, Richard; Bamberg, Michael; Dichgans, Johannes; Weller, Michael

    2004-08-30

    In this single-center retrospective study, 155 consecutive patients with leptomeningeal metastasis (LM) were analyzed for the prognostic role of patient- and therapy-related variables. Ten percent of the patients received radiotherapy alone, 32% had chemotherapy alone, 31% received radiochemotherapy, 17% had supportive therapy only, and 10% were not evaluable for therapy. Chemotherapy was systemic (17%), combined systemic and intrathecal (10%), or intrathecal only (35%). Clinical improvement was noted in 41% of the patients. Overall median survival time (MST) was 4.8 months. Survival varied considerably depending on the type of primary tumor in this largest published cohort of LM patients. Univariate Cox regression analysis revealed that age >60 and elevated cerebrospinal fluid (CSF) albumin or lactate levels were therapy-independent predictors of poor survival in the entire cohort as well as in the subgroup of patients with systemic primary tumors (n=105). The assessment of three therapy-independent parameters allows to group LM patients into groups of low, intermediate, and high risk of poor survival. Moreover, the application of systemic chemotherapy was a positive prognostic factor in patients with subarachnoid lesions detected by neuroimaging (RR 1.94, p=0.001) or with extra-CNS tumor deposits (RR 1.52, p=0.05). The results of this study suggest that systemic chemotherapy alone or in combination with other therapeutic modalities may improve outcome in patients with subarachnoid tumor cell deposits detectable by neuroimaging. PMID:15337619

  16. Posterior urethral valve: Prognostic factors and renal outcome

    PubMed Central

    Bhadoo, Divya; Bajpai, Minu; Panda, Shasanka Shekhar

    2014-01-01

    Objective: The aim was to study the outcome of posterior urethral valve (PUV) cases treated by stepladder protocol and the prognostic factors affecting the outcome. Materials and Methods: Hospital records of all PUV patients treated by stepladder protocol between January 1992 and December 2013 were reviewed. The studied parameters were: Age at presentation, serum creatinine, types of surgical intervention, vesicoureteral reflux (VUR) on initial voiding cystourethrogram (VCUG), renal cortical scars, plasma renin activity (PRA), and glomerular filtration rate (GFR). Results: Of 396 PUV patients treated during the study period, 152 satisfied study criteria. The age at presentation ranged from 2 days to 15 years (mean 31.3 months). The mean follow-up period was 5 years (range: 2-18 years). Primary endoscopic valve ablation was the most common initial procedure. Chronic renal failure was seen in 42.7% patients at the last follow-up. Serum creatinine at presentation, initial PRA levels, initial GFR, and PRA levels at last follow-up were significant predictors of final renal outcome. Age at presentation (<1 vs. >1 year), presence/absence of VUR on initial VCUG and renal cortical scars had no significant correlation with ultimate renal function. Conclusion: Our study confirms the high prognostic significance of initial serum creatinine, PRA levels and GFR in cases with PUV. PRA also holds promise in long-term follow-up of these patients as a marker of progressive renal damage. PMID:25197189

  17. Prognostic factors of phyllodes tumor of the breast.

    PubMed

    Roa, Juan Carlos; Tapia, Oscar; Carrasco, Paula; Contreras, Enrique; Araya, Juan Carlos; Muñoz, Sergio; Roa, Iván

    2006-06-01

    The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior. PMID:16704494

  18. Prognostic significance of survivin expression in renal cell cancer and its correlation with radioresistance.

    PubMed

    Lei, Yu; Geng, Zhang; Guo-Jun, Wu; He, Wang; Jian-Lin, Yuan

    2010-11-01

    Survivin, an important inhibitor of apoptosis, has been found to play an important role in the initiation, progression, and chemoradioresistance of human malignancies. Previously, we have reported that upregulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance. The aim of this study was to assess prognostic significance of survivin protein expression in RCC and analyze its correlation with radiosensitivity of RCC cells. RT-PCR and Western blot assays were performed to detect survivin mRNA and protein expression in normal human kidney epithelial cell line (HKEC) or RCC cell lines. The expression of survivin mRNA in RCC and corresponding nontumor kidney tissues was also detected by RT-PCR. Immunohistochemistry was performed to determine survivin protein expression in 75 cases of RCC tissue samples. Moreover, the association of survivin protein expression with clinicopathogical factors and prognosis of RCC patients was statistically analyzed. Small interfering RNA was used to knockdown the endogenous survivin expression in RCC cell line (ACHN) and evaluate the effects of survivin knockdown on proliferation, apoptosis, and radiosensitivity of RCC cell line. RCC cells showed sufficient expression of survivin mRNA and protein, but the expression of survivin gene was not detected in normal HKEC. Moreover, the expression level of survivin mRNA in RCC tissues was significantly higher than that in corresponding nontumor kidney tissues. The immunostaining of survivin protein was mainly located in cytoplasm of RCC tumor cells. Tumor pathological stage (P = 0.028), grade (P = 0.004), and lymph node metastasis (P = 0.017) of RCC patients were significantly correlated with survivin protein expression. In addition, patients with high survivin levels had a significantly shorter overall survival than those with low levels (P < 0.001), and the expression of survivin protein was an independent prognostic factor for RCC patients (P = 0

  19. Prognostic significance of β2-adrenergic receptor expression in malignant melanoma.

    PubMed

    Shimizu, Akira; Kaira, Kyoichi; Mori, Keita; Kato, Madoka; Shimizu, Kimihiro; Yasuda, Masahito; Takahashi, Ayumi; Oyama, Tetsunari; Asao, Takayuki; Ishikawa, Osamu

    2016-05-01

    Recent studies cite β2-adrenergic receptor (β2AR) antagonists as novel therapeutic agents for melanoma, as they may reduce the disease progression. The β2AR has shown to be expressed in malignant melanoma. However, it remains unclear whether the β2AR expression has a clinical and pathological significance in patients with cutaneous malignant melanoma. We herein conducted a clinicopathological study to investigate the protein expression of β2AR in malignant melanoma of the skin and its prognostic significance. One hundred thirty-three patients with surgically resected cutaneous malignant melanoma were evaluated. Tumor sections were stained by immunohistochemistry for β2AR, Ki-67, the microvessel density (MVD) determined by CD34, and p53. β2AR was highly expressed in 44.4 % (59 out of 133) of the patients. The expression of β2AR was significantly associated with the tumor thickness, ulceration, T factor, N factor, disease stage, tumor size, cell proliferation (Ki-67), and MVD (CD34). Using Spearman's rank test, the β2AR expression was correlated with Ki-67 (r = 0.278; 95 % CI, 0.108 to 0.432; P = 0.001), CD34 (r = 0.445; 95 %CI, 0.293 to 0.575; P < 0.001), and the tumor size (r = 0.226; 95 % CI, 0.053 to 0.386; P = 0.008). Using a univariate analysis, the tumor thickness, ulceration, disease stage, β2AR, Ki-67, and CD34 had a significant relationship with the overall and progression-free survivals. A multivariable analysis confirmed that β2AR was an independent prognostic factor for predicting a poor overall survival (HR 1.730; 95 % CI 1.221-2.515) and progression-free survival (HR 1.576; 95 % CI 1.176-2.143) of malignant melanoma of the skin. β2AR can serve as a promising prognostic factor for predicting a worse outcome after surgical treatment and may play an important role in the development and aggressiveness of malignant melanoma. PMID:26596834

  20. TPX2 in human clear cell renal carcinoma: Expression, function and prognostic significance

    PubMed Central

    CHEN, QI; CAO, BIN; NAN, NING; WANG, YU; ZHAI, XU; LI, YOUFANG; CHONG, TIE

    2016-01-01

    Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein. TPX2 is considered to be an important gene in tumorigenesis; however, the particular function of TPX2 in the development of human renal cell carcinoma (RCC) is unknown. In the present study, the expression, function and prognostic significance of TPX2 in human RCC was analyzed. A total of 286 tissue samples from patients with RCC who had undergone nephrectomies were utilized. Subsequently, the expression of TPX2 protein was investigated using immunohistochemistry and western blotting, and TPX2 mRNA expression was examined using reverse transcription-quantitative polymerase chain reaction. To establish the effect of TPX2 on the proliferation and invasion of the RCC cells, TPX2 expression was increased by stable transfection with a TPX2 vector and TPX2 expression was decreased using small interfering RNA. Proliferation of the RCC cells was analyzed using a WST-1 assay and an animal xenograft model with BALB/c nude mice, whilst invasion of the RCC cells was examined using a Matrigel-coated invasion chamber. It was demonstrated that TPX2 expression was significantly higher in the RCC tissues compared with normal kidney tissues (P<0.05). Furthermore, TPX2 expression was associated with tumor size, histological grade and tumor stage (P<0.05), and was observed to markedly increase the proliferation and invasion of the RCC cells. It may be concluded that the expression of TPX2 is significantly upregulated in RCC tissue, subsequently increasing the proliferative and invasive ability of RCC cells. Therefore, the protein may serve as a therapeutic target and independent prognostic factor in the treatment of human RCC. PMID:27123144

  1. The prognostic significance of surface dipeptidylpeptidase IV (CD26) expression in B-cell chronic lymphocytic leukemia.

    PubMed

    Matuszak, Magdalena; Lewandowski, Krzysztof; Czyż, Anna; Kiernicka-Parulska, Jolanta; Przybyłowicz-Chalecka, Anna; Jarmuż-Szymczak, Małgorzata; Lewandowska, Maria; Komarnicki, Mieczysław

    2016-08-01

    A number of factors related to B-cell chronic lymphocytic leukemia (B-CLL) patients' prognosis have been identified. However, still some factors better reflecting disease activity in individual cases are explored. The study aimed to evaluate prognostic significance of dipeptidylpeptidase IV/CD26 expression on B-CLL cells and its relationship with other well established prognostic factors. The study included 94 patients with newly diagnosed B-CLL and involved analysis of clinical, laboratory, flow-cytometry and cytogenetic data. Detailed analysis showed that CD26 expression on B-CLL cells correlates with Rai's clinical stage of the disease at diagnosis (p=0.034), β2-microglobulin concentration (p=0.012), lactic acid dehydrogenase activity (p=0.045) and absolute lymphocytes' count (p=0.027) in the blood. The multivariate analysis revealed that time to treatment (TTT) was significantly influenced by Rai clinical stage, LDH activity in blood and CD26 expression on B-CLL cell's. Moreover, in the multivariate analysis restricted to the group of patients with documented cytogenetic risk (n=36) CD26 expression, Rai clinical stage and cytogenetic profile remained their independent impact on TTT. The results of our study indicate that the CD26 expression should be incorporated in B-CLL patients risk assessment along with well known prognostic factors, since it seems to have a relationship with the tumor mass and influences TTT. PMID:27376546

  2. Cytokines and Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Jammal, Millena Prata; Martins-Filho, Agrimaldo; Silveira, Thales Parenti; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2016-01-01

    INTRODUCTION Ovarian cancer has a high mortality and delayed diagnosis. Inflammation is a risk factor for ovarian cancer, and the inflammatory response is involved in almost all stages of tumor development. Immunohistochemical staining in stroma and epithelium of a panel of cytokines in benign and malignant ovarian neoplasm was evaluated. In addition, immunostaining was related to prognostic factors in malignant tumors. METHOD The study group comprised 28 ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5, IL-6, and IL-10; and TNFR1). Chi-square test with Yates’ correction was used, which was considered significant if less than 0.05. RESULTS TNFR1, IL-5, and IL-10 had more frequent immunostaining 2/3 in benign neoplasms compared with malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2 in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of the ovarian cancer stroma showed that histological grade 3 was significantly correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more frequently. CONCLUSION IL-2 and TNFR1 stromal immunostaining are related prognostic factors in ovarian cancer and can be the target of new therapeutic strategies. PMID:27512342

  3. Expression profile and prognostic value of NNMT in patients with pancreatic cancer

    PubMed Central

    Zheng, Dong-Hui; Wu, Nan; Zhu, Lun; Xing, Changying; Zhu, Jin

    2016-01-01

    The elevation of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer tissues and cell lines, but its clinical and prognostic implications remain controversial. This study aimed at investigating the expression of NNMT in pancreatic benign and malignant tissues and the prognostic value of NNMT in pancreatic cancer. The expression of NNMT in tissue specimens of 28 chronic pancreatitis patients and 178 pancreatic cancer patients were assayed with immunohistochemistry on tissue microarray. The NNMT expression levels of pancreatic patients were correlated with their clinicopathological characteristics. The influences of NNMT expression and patients' clinicopathological characteristics on overall survival (OS) were analyzed. The percentage of NNMT high expression (NNMTh) in pancreatic cancer (55.6%) was significantly higher than those in chronic pancreatitis (21.4%) and paracancerous tissues (14.8%) (p < 0.001). NNMTh tends to significantly correlate with unfavorable clinicopathological features such as age > 60 years old (p = 0.014), tumor diameter > 4 cm (p < 0.001), TNM stage III or IV (p < 0.001) and poor tumor differentiation (p = 0.004). The median OS of patients with NNMTh and NNMTl were 7.0 months (95% CI: 5.275–8.725) and 11.5 months (95% CI: 9.759–13.241) respectively (p = 0.005). On multivariate analysis, NNMTl (hazards ratio [HR]: 0.399; 95% CI: 0.284–0.560; p < 0.001), absence of neurological involvement (HR: 0.651; 95% CI: 0.421–0.947; p = 0.041), TNM stage I or II (HR: 0.506; 95% CI: 0.299–0.719; p = 0.015) and well tumor differentiation (HR: 0.592; 95% CI: 0.319–0.894; p = 0.044) were significant favorable prognostic factors of OS. In conclusion, NNMT is upregulated in pancreatic cancer, correlates with unfavorable clinicopathological features and may serve as an independent prognosticator of patients' survival. PMID:26942567

  4. Prognostic value of ALDH1 expression in lung cancer: a meta-analysis

    PubMed Central

    Huo, Wei; Du, Min; Pan, Xinyan; Zhu, Xiaomin; Li, Zhimin

    2015-01-01

    Objective: ALDH1 has recently been reported as a marker of cancer stem-like cells in lung cancer. However, the predictive value of ALDH1 in lung cancer remains controversial. In this study, we aimed to evaluate the association of ALDH1 expression with the clinicopathological features and outcomes of lung cancer patients through a meta-analysis. Methods: Publications that assessed the clinical or prognostic significance of ALDH1 in lung cancer up to October 2014 were identified. A meta-analysis was performed to clarify the association between ALDH1 expression and clinical outcomes. Results: Ten eligible publications with 1836 patients were included. The analysis of these data showed that ALDH1 expression was highly correlated with lymph node metastasis (pooled OR = 1.45, 95% CI: 1.04-2.02, P = 0.027), decreased overall survival (pooled RR: 2.25, 95% CI: 1.15-4.41, P = 0.019), and decreased disease-free survival (pooled RR: 1.63, 95% CI: 1.01-2.64, P = 0.047). Conclusion: Patients with ALDH1-positive lung cancer had poor prognosis, which was associated with common clinicopathological poor prognostic factors. PMID:25932135

  5. EphA4 is a prognostic factor in gastric cancer

    PubMed Central

    2013-01-01

    Background Erythropoietin-producing hepatocellular (Eph) receptor, consisting of a family of receptor tyrosine kinases, plays critical roles in tumour development and is considered an attractive target for cancer therapy. Methods Tumour samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy. The expressions of EphA2, EphA4, and ephrinA1 were evaluated immunohistochemically. Results High expressions of EphA2, EphA4, and ephrinA1 significantly correlated with variables related to tumour progression, including the depth of invasion, metastatic lymph nodes, pathological stage, and distant metastasis or recurrent disease. High expressions of EphA2, EphA4, and ephrinA1 were significantly associated with poorer disease-specific survival (DSS; p < 0.001, p < 0.001, p = 0.026). On multivariate analysis, EphA4 was an independent prognostic factor of DSS (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.1-4.8; p = 0.028), and EphA2 tended to be a prognostic factor (HR, 2.4; 95% CI, 1.0-5.8; p = 0.050). In stage II and III cancer, EphA4 and EphA2 were both significantly associated with shorter survival (p = 0.007 and 0.019), but only EphA2 was an independent prognostic factor (HR, 2.6; 95% CI, 1.1-6.3; p = 0.039). Conclusion EphA4 may play important roles in tumor progression and outcomes in patients with gastric cancer. PMID:23738943

  6. Nuclear PARP1 expression and its prognostic significance in breast cancer patients.

    PubMed

    Mazzotta, Annalisa; Partipilo, Giulia; De Summa, Simona; Giotta, Francesco; Simone, Giovanni; Mangia, Anita

    2016-05-01

    Poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP1) plays important roles in DNA damage response pathways and is often overexpressed in various human tumors. Currently, the use of PARP inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. The aim was to investigate the clinicopathological and prognostic significance of PARP1 in BC patients. The PARP1 and breast cancer susceptibility gene 1 (BRCA1) protein expressions were evaluated in 114 BCs by immunohistochemistry. Disease-free survival (DFS) and overall survival (OS) were determined based on the Kaplan-Meier method. Our results showed that nuclear PARP1 expression was significantly associated with peritumoral vascular invasion (P = 0.046), chemotherapeutic treatment (P = 0.026), oestrogen receptor (ER; P = 0.013), human epidermal growth factor receptor 2 (HER2; P = 0.003) and BRCA1 (P < 0.001) expression. Survival analyses showed a significant association with clinical outcome in the subgroup of ER-negative patients (P = 0.017 for DFS and P = 0.048 for OS) and in the subgroup of patients treated with chemotherapeutic agents (P = 0.042 for DFS and P = 0.046 for OS). A significant correlation was also found for DFS in patients characterized by tumors without peritumoral vascular invasion (P = 0.022). More importantly, multivariate analyses revealed that high nuclear PARP1 expression was associated with decreased DFS (P = 0.012) and OS (P = 0.026). In conclusion, PARP1 expression may be used as an independent prognostic factor in BC patients. In addition, this study demonstrated that high PARP1 expression may represent a marker of poorer prognosis both for patients with worse clinical outcome and in less aggressive clinical conditions. PMID:26614429

  7. Cancer of the glottis: prognostic factors in radiation therapy

    SciTech Connect

    Mantravadi, R.V.; Liebner, E.J.; Haas, R.E.; Skolnik, E.M.; Applebaum, E.L.

    1983-10-01

    The authors conducted a multivariate analysis of the prognostic factors in 96 patients with early glottic cancer treated by radiation therapy. Of these, 73 had T1 and 23 had T2 tumor. The primary tumor was controlled in 82% of T1 and 74% of T2 lesions. Actuarial five-year survival rates were 87% for T1 and 74% for T2. Carcinoma of the anterior commissure associated with bilateral vocal cord involvement, subglottic tumor extension, persistent or recurrent laryngeal edema, and impaired cord mobility was found to adversely influence the prognosis. The data suggest that irradiation is the treatment of choice for glottic cancer limited to the vocal cords or with minimal extension to the anterior commissure or supraglottic larynx.

  8. Cancer of the glottis: prognostic factors in radiation therapy

    SciTech Connect

    Mantravadi, R.V.P.; Liebner, E.J.; Haas, R.E.; Skolnik, E.M.; Applebaum, E.L.

    1983-10-01

    The authors conducted a multivariate analysis of the prognostic factors in 96 patients with early glottic cancer treated by radiation therapy. Of these, 73 had T/sub 1/ and 23 had T/sub 2/ tumor. The primary tumor was controlled in 82% of T/sub 1/ amd 74% for T/sub 2/. Carcinoma of the anterior commissure associated with bilateral vocal cord involvement, subglottic tumor extension, persistent or recurrent laryngeal edema, and impaired cord mobility was found to adversely influence the prognosis. The data suggest that irradiation is the treatment of choice for glottic cancer limited to the vocal cords or with minimal extension to the anterior commissure or gupraglottic larynx.

  9. Intrahepatic Cholangiocarcinoma Progression: Prognostic Factors and Basic Mechanisms

    PubMed Central

    Sirica, Alphonse E.; Dumur, Catherine I.; Campbell, Deanna J. W.; Almenara, Jorge A.; Ogunwobi, Olorunseun O.; Dewitt, Jennifer L.

    2013-01-01

    In this review, we will examine various molecular biomarkers for their potential to serve as independent prognostic factors for predicting survival outcome in postoperative patients with progressive intrahepatic cholangiocarcinoma. Specific rodent models of intrahepatic cholangiocarcinoma that mimic relevant cellular, molecular, and clinical features of the human disease are also described, not only in terms of their usefulness in identifying molecular pathways and mechanisms linked to cholangiocarcinoma development and progression, but also for their potential value as preclinical platforms for suggesting and testing novel molecular strategies for cholangiocarcinoma therapy. Last, recent studies aimed at addressing the role of desmoplastic stroma in promoting intrahepatic cholangiocarcinoma progression are highlighted in an effort to underline the potential value of targeting tumor stromal components together with that of cholangiocarcinoma cells as a novel therapeutic option for this devastating cancer. PMID:19896103

  10. Prognostic significance of Ki-67 antigen expression in extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Jiang, Li; Li, Pengfei; Wang, Hua; Liu, Jun; Zhang, Xinke; Qiu, Huijuan; Zhang, Bei

    2014-10-01

    Extranodal natural killer (NK)/T-cell lymphoma, nasal-type (ENKTL) is a clinically heterogeneous disease with poor prognosis and requires risk stratification in affected patients. Recent studies have shown that Ki-67 may serve as a prognostic marker in certain types of lymphoma. We analyzed Ki-67 expression and its correlation with prognosis in 182 patients with ENKTL from January 2002 to June 2013. The patients were classified into two groups through a median value: low (<60%) versus high Ki-67 (≥60%). High Ki-67 expression was more common in patients with B symptoms (p=0.02), bulky disease (p=0.001), and extraupper aerodigestive tract NK/T-cell lymphoma (p=0.001). High Ki-67 expression was significantly associated with poor overall survival (p<0.0001) and progression-free survival (p<0.0001). For patients with low-risk IPI or KPI, Ki-67 at diagnosis could contribute to distinguish patients with favorable outcomes from those with poor outcomes. The results of multivariate analysis showed that the high Ki-67 expression is an independent prognostic factor for overall survival and progression-free survival. (OS, p=0.001; PFS, p=0.003). Our data showed that Ki-67 is an effective prognostic indicator of survival in ENKTL patients. This prognostic index may be helpful in identifying high-risk patients with ENKTL. PMID:25204411

  11. Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor

    PubMed Central

    Song, Fengju; Zheng, Hong; Chen, Kexin; Zhang, Wei; Yang, Jilong

    2016-01-01

    Background Malignant peripheral nerve sheath tumors (MPNST) are rare, highly malignant, and poorly understood sarcomas. The often poor outcome of MPNST highlights the necessity of identifying prognostic predictors for this aggressive sarcoma. Here, we investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs. Results aCGH and bioinformatics analysis identified frequent amplification of the FGFR1 gene. FISH analysis revealed that 26.9% MPNST samples had amplification of FGFR1, with both focal and polysomy patterns observed. IHC identified that FGFR1 protein expression was positively correlated with FGFR1 gene amplification. High expression of FGFR1 protein was associated with better overall survival (OS) and was an independent prognostic predictor for OS of MPNST patients. Additionally, combined expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better OS. FGFR4 protein was expressed 82.3% of MPNST samples, and was associated with poor disease-free survival. Materials and Methods We performed microarray-based comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Medical University Cancer Institute and Hospital. Fluorescence in situ hybridization (FISH) was used to validate the gene amplification detected by aCGH analysis. Another cohort of 63 formalin-fixed paraffin-embedded MPNST samples (including 52 samples for FISH assay) was obtained to explore FGFR1, 2, 3, and 4 protein expression by immunohistochemical (IHC) analysis. Conclusions Our integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST. PMID:26993773

  12. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

    PubMed Central

    Demichelis, Sandra O; Isla-Larrain, Marina T; Cermignani, Luciano; Alberdi, Cecilio G; Segal-Eiras, Amada; Croce, María Virginia

    2011-01-01

    Objective In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis. Results All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased. Conclusion Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer. PMID:24367185

  13. The Characteristics and Prognostic Effect of E-Cadherin Expression in Colorectal Signet Ring Cell Carcinoma

    PubMed Central

    Wang, Renjie; Ma, Xiaoji; Li, Yaqi; He, Yiping; Huang, Dan; Cai, Sanjun; Peng, Junjie

    2016-01-01

    Purpose Signet ring cell carcinoma (SRCC) is rare. The aim of this study is to understand the clinicopathological features and identify the possible prognostic factors in colorectal SRCC. Methods Patients with SRCC who underwent primary lesion resection at Fudan University Shanghai Cancer Center from September 2008 to July 2014 were retrospectively analyzed. Patient’s gender, age, tumor location, depth of invasion, lymph node metastasis, synchronous distant metastasis, perineural invasion, lymphovascular invasion, and E-cadherin expression were studied with prognosis, and the correlation between E-cadherin expression and clinicopathological features were analyzed. All clinicopathological and molecular factors were put into multivariate analysis using Cox proportional hazards model for detecting independent prognostic factors. Results 59 patients accounting for 0.89% of total colorectal cancer patients met the criteria and were enrolled in the study. The median survival time is 28.9 months, and the 3-year survival rate is 62.7%. SRCC were seen more common in young male patients. Advanced stage was more common in SRCC, 58 (98.3%) patients had T3/T4 lesions, 52 (88.1%) patients had lymph node metastasis, and 14 (23.7%) patients had distant metastasis. Distant metastases were seen more common in peritoneal cavity. Distant metastasis (HR = 4.194, 95% CI: 1.297–13.567), lymphovascular invasion (HR = 2.888, 95% CI: 1.115–7.483), and E-cadherin expression (HR = 0.272, 95% CI: 0.096–0.768) were independent predictors for survival. Conclusions SRCC is a rare subtype of colorectal cancer with poor prognosis. Distant metastasis, lymphovascular invasion, and E-cadherin expression can predict prognosis of colorectal SRCCs independently. More precise therapy and more close surveillance are needed for these patients. PMID:27509205

  14. Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era

    PubMed Central

    Vaidya, R.; Witzig, T. E.

    2014-01-01

    Background The introduction of rituximab (R) to conventional CHOP chemotherapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) led to an unequivocal improvement in survival, establishing RCHOP as the standard of care. Still, nearly 40% of DLBCL patients will eventually die of relapsed disease. Efforts to improve outcomes by addition of new biologic agents (X) to the RCHOP backbone are underway. In this era of R(X)CHOP, it is imperative to develop prognostic and predictive markers, not only to identify patients who will suffer a particularly aggressive course, but also to accurately select patients for clinical trials from which they will most benefit. Design The following review was undertaken to describe prognostic factors in DLBCL, with emphasis on markers that are accurate, relatively available, and clinically applicable in 2014. Results The International Prognostic Index retains its validity in the era of RCHOP, although with limited ability to predict those with <50% chance of long-term survival. Gene expression profiling has provided novel insights into the biology of DLBCL and led to the development of immunohistochemistry (IHC) algorithms that are in routine practice. Identification of a ‘double-hit’ (DH) lymphoma by fluorescent in situ hybridization with aberrations involving MYC and/or BCL2 and BCL6 genes has important implications due to its extremely dismal prognosis with RCHOP. Other markers such as the absolute lymphocyte count (ALC), serum immunoglobulin free light chains, vitamin D levels, serum cytokines/chemokines, and imaging with positron emission tomography (PET) have all shown promise as future predictive/prognostic tests. Conclusions The future for new treatment options in DLBCL is promising with current clinical trials testing novel targeted agents such as bortezomib, lenalidomide, and ibrutinib as the ‘X’ in R(X)CHOP. Predictive factors are required to select and randomize patients appropriately for these trials. We

  15. [Prognostic value of the inmunohïstochemical expression of protein p27KIP1 in laryngeal cancer].

    PubMed

    García Lozano, M C; Orradre Romero, J L; Caro García, M; Martínez Alvarez, A; Lasso Luis, O; Piris Pinilla, M A

    2006-01-01

    In this paper we carried out an immunohistochemical study of protein p27KIP1 expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain). In the cases with lymph node metastasis we also studied p27KIP1 expression at this level. Furthermore we have analysed the value of protein p27KIP1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between p27KIP1 expression and other clinic and pathologic parameters. PMID:16566195

  16. Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?

    PubMed Central

    Gruber, Günther; Greiner, Richard H; Hlushchuk, Ruslan; Aebersold, Daniel M; Altermatt, Hans J; Berclaz, Gilles; Djonov, Valentin

    2004-01-01

    Background Hypoxia-inducible factor 1 alpha (hif-1α) furnishes tumor cells with the means of adapting to stress parameters like tumor hypoxia and promotes critical steps in tumor progression and aggressiveness. We investigated the role of hif-1α expression in patients with node-positive breast cancer. Methods Tumor samples from 77 patients were available for immunohistochemistry. The impact of hif-1α immunoreactivity on survival endpoints was determined by univariate and multivariate analyses, and correlations to clinicopathological characteristics were determined by cross-tabulations. Results hif-1α was expressed in 56% (n = 43/77) of the patients. Its expression correlated with progesterone receptor negativity (P = 0.002). The Kaplan–Meier curves revealed significantly shorter distant metastasis-free survival (DMFS) (P = 0.04, log-rank) and disease-free survival (DFS) (P = 0.04, log-rank) in patients with increased hif-1α expression. The difference in overall survival (OS) did not attain statistical significance (5-year OS, 66% without hif-1α expression and 55% with hif-1α expression; P = 0.21). The multivariate analysis failed to reveal an independent prognostic value for hif-1α expression in the whole patient group. The only significant parameter for all endpoints was the T stage (T3/T4 versus T1/T2: DMFS, relative risk = 3.16, P = 0.01; DFS, relative risk = 2.57, P = 0.03; OS, relative risk = 3.03, P = 0.03). Restricting the univariate and multivariate analyses to T1/T2 tumors, hif-1α expression was a significant parameter for DFS and DMFS. Conclusions hif-1α is expressed in the majority of patients with node-positive breast cancer. It can serve as a prognostic marker for an unfavorable outcome in those with T1/T2 tumors and positive axillary lymph nodes. PMID:15084243

  17. Downregulation of MTSS1 expression is an independent prognosticator in squamous cell carcinoma of the lung

    PubMed Central

    Kayser, G; Csanadi, A; Kakanou, S; Prasse, A; Kassem, A; Stickeler, E; Passlick, B; zur Hausen, A

    2015-01-01

    Background: The metastasis suppressor 1 (MTSS1) is a newly discovered protein putatively involved in tumour progression and metastasis. Material and Methods: Immunohistochemical expression of MTSS1 was analysed in 264 non-small-cell lung carcinomas (NSCLCs). Results: The metastasis suppressor 1 was significantly overexpressed in NSCLC compared with normal lung (P=0.01). Within NSCLC, MTSS1 expression was inversely correlated with pT-stage (P=0.019) and histological grading (P<0.001). NSCLC with MTSS1 downregulation (<20%) showed a significantly worse outcome (P=0.007). This proved to be an independent prognostic factor in squamous cell carcinomas (SCCs; P=0.041), especially in early cancer stages (P=0.006). Conclusion: The metastasis suppressor 1 downregulation could thus serve as a stratifying marker for adjuvant therapy in early-stage SCC of the lung. PMID:25625275

  18. An mRNA expression signature for prognostication in de novo acute myeloid leukemia patients with normal karyotype

    PubMed Central

    Chou, Wen-Chien; Hou, Hsin-An; Tseng, Mei-Hsuan; Kuo, Yi-Yi; Chen, Yidong; Chuang, Eric Y.; Tien, Hwei-Fang

    2015-01-01

    Although clinical features, cytogenetics, and mutations are widely used to predict prognosis in patients with acute myeloid leukemia (AML), further refinement of risk stratification is necessary for optimal treatment, especially in cytogenetically normal (CN) patients. We sought to generate a simple gene expression signature as a predictor of clinical outcome through analyzing the mRNA arrays of 158 de novo CN AML patients. We compared the gene expression profiles of patients with poor response to induction chemotherapy with those who responded well. Forty-six genes expressed differentially between the two groups. Among them, expression of 11 genes was significantly associated with overall survival (OS) in univariate Cox regression analysis in 104 patients who received standard intensive chemotherapy. We integrated the z-transformed expression levels of these 11 genes to generate a risk scoring system. Higher risk scores were significantly associated with shorter OS (median 17.0 months vs. not reached, P < 0.001) in ours and another 3 validation cohorts. In addition, it was an independent unfavorable prognostic factor by multivariate analysis (HR 1.116, 95% CI 1.035~1.204, P = 0.004). In conclusion, we developed a simple mRNA expression signature for prognostication in CN-AML patients. This prognostic biomarker will help refine the treatment strategies for this group of patients. PMID:26517675

  19. Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis

    PubMed Central

    van Kuijk, Simon J. A.; Yaromina, Ala; Houben, Ruud; Niemans, Raymon; Lambin, Philippe; Dubois, Ludwig J.

    2016-01-01

    Hypoxia is a characteristic of many solid tumors and an adverse prognostic factor for treatment outcome. Hypoxia increases the expression of carbonic anhydrase IX (CAIX), an enzyme that is predominantly found on tumor cells and is involved in maintaining the cellular pH balance. Many clinical studies investigated the prognostic value of CAIX expression, but most have been inconclusive, partly due to small numbers of patients included. The present meta-analysis was therefore performed utilizing the results of all clinical studies to determine the prognostic value of CAIX expression in solid tumors. Renal cell carcinoma was excluded from this meta-analysis due to an alternative mechanism of upregulation. 958 papers were identified from a literature search performed in PubMed and Embase. These papers were independently evaluated by two reviewers and 147 studies were included in the analysis. The meta-analysis revealed strong significant associations between CAIX expression and all endpoints: overall survival [hazard ratio (HR) = 1.76, 95% confidence interval (95%CI) 1.58–1.98], disease-free survival (HR = 1.87, 95%CI 1.62–2.16), locoregional control (HR = 1.54, 95%CI 1.22–1.93), disease-specific survival (HR = 1.78, 95%CI 1.41–2.25), metastasis-free survival (HR = 1.82, 95%CI 1.33–2.50), and progression-free survival (HR = 1.58, 95%CI 1.27–1.96). Subgroup analyses revealed similar associations in the majority of tumor sites and types. In conclusion, these results show that patients having tumors with high CAIX expression have higher risk of locoregional failure, disease progression, and higher risk to develop metastases, independent of tumor type or site. The results of this meta-analysis further support the development of a clinical test to determine patient prognosis based on CAIX expression and may have important implications for the development of new treatment strategies. PMID:27066453

  20. CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer

    PubMed Central

    Yoshida, Kazumichi; Tsujimoto, Hironori; Matsumura, Kouji; Kinoshita, Manabu; Takahata, Risa; Matsumoto, Yusuke; Hiraki, Shuichi; Ono, Satoshi; Seki, Shuhji; Yamamoto, Junji; Hase, Kazuo

    2015-01-01

    CD47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD47 expression in gastric cancer is not well documented. Immunohistochemical expression of CD47 in surgical specimens was investigated. Expression of CD47 and CD44, a known gastric cancer stem cell marker, were investigated in gastric cancer cell lines by flow cytometry. MKN45 and MKN74 gastric cancer cells were sorted by fluorescence-activated cell sorting according to CD44 and CD47 expression levels, and their in vitro proliferation, spheroid-forming capacity, and in vivo tumorigenicity were studied. In vitro phagocytosis of cancer cells by human macrophages in the presence of a CD47 blocking monoclonal antibody (B6H12) and the survival of immunodeficient mice intraperitoneally engrafted with MKN45 cells and B6H12 were compared to experiments using control antibodies. Immunohistochemistry of the clinical specimens indicated that CD47 was positive in 57 out of 115 cases, and its positivity was an independent adverse prognostic factor. Approximately 90% of the MKN45 and MKN74 cells expressed CD47 and CD44. CD47hi gastric cancer cells showed significantly higher proliferation and spheroid colony formation than CD47lo, and CD44hiCD47hi cells showed the highest proliferation in vitro and tumorigenicity in vivo. B6H12 significantly enhanced in vitro phagocytosis of cancer cells by human macrophages and prolonged the survival of intraperitoneal cancer dissemination in mice compared to control antibodies. In conclusion, CD47 is an adverse prognostic factor and promising therapeutic target in gastric cancer. PMID:26077800

  1. Prognostic factors for clinical outcomes after rotator cuff repair

    PubMed Central

    Pécora, José Otávio Reggi; Malavolta, Eduardo Angeli; Assunção, Jorge Henrique; Gracitelli, Mauro Emílio Conforto; Martins, João Paulo Sobreiro; Ferreira, Arnaldo Amado

    2015-01-01

    OBJECTIVE: To identify prognostic factors of postoperative functional outcomes. METHODS: Retrospective case series evaluating patients undergoing rotator cuff repair, analyzed by the UCLA score (pre and 12-month postoperative) and Magnetic Resonance Imaging (preoperative). Patients' intrinsic variables related to the injury and intervention were evaluated. Multivariate linear regression analysis was performed to determine variables impact on postoperative functional assessment. RESULTS: 131 patients were included. The mean UCLA score increased from 13.17 ± 3.77 to 28.73 ± 6.09 (p<0,001). We obtained 65.7% of good and excellent results. Age (r= 0.232, p= 0.004) and reparability of posterosuperior injuries (r= 0.151, p= 0.043) correlated with the functional assessment at 12 months. After multivariate linear regression analysis, only age was associated (p = 0.008). CONCLUSIONS: The surgical treatment of rotator cuff tears lead to good and excellent results in 65.6% of patients. Age was an independent predictor factor with better clinical outcomes by UCLA score in older patients. Level of Evidence IV, Case Series. PMID:26207092

  2. The expression of plakoglobin is a potential prognostic biomarker for patients with surgically resected lung adenocarcinoma

    PubMed Central

    He, Xiaobo; Zhou, Ting; Yang, Guangwei; Fang, Wenfeng; Li, Zelei; Zhan, Jianhua; Zhao, Yuanyuan; Cheng, Zhibin; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2016-01-01

    Purpose This study aimed to explore the relationship between plakoglobin expression and clinical data in the patients with surgically resected lung adenocarcinoma. Results With follow-up of median 50.14 months, the average PFS and OS were 16.82 and 57.92 months, respectively. In 147 patients, recurrence or death was observed in 131 patients. According to the log-rank test, low plakoglobin expression was a significant predictor for favorable DFS (P=0.006) and OS (P=0.043). For the analyses within subgroups, high plakoglobin expression was an independent factor for reducing DFS in non-metastatic patients with resected lung adenocarcinoma (P < 0.05). Moreover, high plakoglobin expression was associated with poor DFS even receiving adjuvant chemotherapy (P =0.028) and with a shorter DFS (HR, 2.01, 95%CIs, 1.35 to 2.97, P=0.001) and OS (HR, 1.94, 95%CIs, 1.12 to 3.37, P=0.019). Patients and methods The expression of plakoglobin in 147 primary tumor tissues was examined by using immunohistochemistry and clinical data were collected. The optimal cutoff value of immunoreactivity score (IRS) was calculated and used to divide all the patients into two groups: low-level group (IRS: 0-3, n=59) and high-level group (IRS: 4-12, n=88). Kaplan–Meier curves were applied to assess the plakoglobin expression and clinical variables. The univariate and multivariate Cox model analyses were performed to evaluate the effects of clinical factors and plakoglobin expression on disease-free survival (DFS) and overall survival (OS). Conclusion High plakoglobin expression is an independent negative prognostic factor for patients with surgically resected lung adenocarcinoma. PMID:26933815

  3. Expression of paxillin in laryngeal squamous cell carcinoma and its prognostic value

    PubMed Central

    Li, Lianqing; Wang, Jing; Gao, Lei; Gong, Lili

    2015-01-01

    Paxillin (PXN) gene has been reported to act as an oncogene in many malignancies and play important roles in the development of human carcinomas. However, the relationship between the expression of PXN and clinicopathological characteristics in human laryngeal carcinoma remains unclear. This study aimed to examine the expression of PXN, and to evaluate the clinical significance of its expression in human laryngeal squamous cell carcinoma (LSCC). Real-time quantitative PCR (qRT-PCR), Western blotting and immunohistochemistry were performed to analyze the expression of PXN in LSCC tissues and corresponding paracancerous normal tissues. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients with LSCC. The expression of PXN was significantly higher in LSCC than in matched paracancerous normal tissues. Immunohistochemical analysis was performed in human LSCC samples and the data were correlated with clinicopathologic features. Levels of PXN in LSCC were related to histopathological grade (P = 0.016), Lymph node metastasis (P = 0.029) and TNM stage (P < 0.001). Kaplan-Meier analysis revealed that survival curves of the overall survival of patients with high PXN expression was significantly worse than that of low PXN expression (P = 0.035). Cox regression analysis revealed that PXN expression level was an independent prognostic factor of the overall survival rate of patients with LSCC (P = 0.002). These findings suggest that PXN expression has potential use as a novel biomarker of LSCC patients and may serve as an independent predictive factor for prognosis of LSCC patients. PMID:26464671

  4. Brainstem gangliogliomas: prognostic factors, surgical indications and functional outcomes.

    PubMed

    Pan, Chang-Cun; Chen, Xin; Xu, Cheng; Wu, Wen-Hao; Zhang, Peng; Wang, Yu; Wu, Tao; Tang, Jie; Xiao, Xin-Ru; Wu, Zhen; Zhang, Jun-Ting; Zhang, Li-Wei

    2016-07-01

    To explore the prognostic factors and discuss the surgical indications of brainstem gangliogliomas. Twenty-one patients with brainstem ganglioglioma were surgically treated at our hospital between 2006 and 2014. The clinical, radiological, operative, and pathological findings of these patients were retrospectively reviewed. The 3-years overall survival and event-free survival (EFS) rates were 90.5 % and 68.4 %, respectively. Four patients (4/18, 22 %) experienced a recurrence with a mean recurrence-free survival of 5.5 months and a mean follow-up of 37 months. Three patients died of surgery-related complications. Three growth patterns were identified: exophytic (6/21), intrinsic (2/21), and endo-exophytic (13/21). Eight patients (8/15, 53 %) harbored a BRAF V600E mutation. All recurrent tumors were endo-exophytic, and except the one without molecular information, were BRAF V600E mutants. A Cox hazard proportion ratio model was used to identify factors influencing EFS, including sex, age, location, growth patterns, extent of resection (EOR), and BRAF V600E mutation status. On univariate analysis, none of these factors reached statistical significance. Among them, EOR and growth patterns were strongly associated with each other (Fisher's exact test, P < 0.01). A multivariate analysis demonstrated that growth patterns were the only factor associated with EFS (P = 0.02; HR 49.05; 95 % CI 1.76-1365.13). Growth patterns may be useful to select surgery candidates and predict prognosis for patients with brainstem gangliogliomas. BRAF V600E was frequently present and appeared to be associated with shorter recurrence-free survival. Studies on BRAF V600E-targeted therapy for patients with high surgical risks are needed. PMID:27112924

  5. Hematogones: a sensitive prognostic factor for Chinese adult patients with acute myeloid leukemia

    PubMed Central

    Li, L.; Fu, R.; Zhang, T.; Xie, X.; Liu, J.; Tao, J.; Song, J.; Liu, H.; Zhang, W.; Lu, W.; Shao, Z.

    2016-01-01

    Background Hematogones (hgs) are normal B-lymphocyte precursors that increase in some hematologic diseases. Many studies indicate that hgs might be a favourable prognostic factor. We thus considered it important to determine whether hgs are also a prognostic factor for Chinese adult patients with acute myeloid leukemia (aml) and whether the hg-positive and hg-negative groups show any serologic or phenotypic differences. Methods Chinese adult aml patients (n = 177) who were all initially hg-negative underwent standard chemotherapy and were thereafter divided into hg-positive and hg-negative groups according to hg levels in bone marrow during their first remission. Results The follow-up study confirmed that survival duration (both leukemia-free and overall) was significantly greater in the hg-positive group than in the hg-negative group and was accompanied by a lower relapse rate. A retrospective study of patient characteristics at the time of first diagnosis revealed some differences between the hg-positive and the hg-negative groups, including elevations in white blood cells, lactate dehydrogenase, and β2-microglobulin in the hg-negative group. Retrospective phenotypic analysis revealed a significantly lower proportion of abnormal chromosome karyotype and CD34 expression in hg-positive patients. Finally, we evaluated whether additional intensive chemotherapy after standard chemotherapy could further increase hgs. Conclusions The present work verified the validity of hgs as a prognostic factor for Chinese adult patients with aml. Compared with hg-negative patients, hg-positive patients not only experienced longer survival and a lower relapse rate, but they also had some serologic and phenotypic characteristics that are all considered indicators of better outcome. Additional intensive chemotherapy could further increase the level of hgs, which might imply better clinical results. PMID:27122980

  6. Prognostic Factors and Survival in Pediatric and Adolescent Liposarcoma

    PubMed Central

    Stanelle, Eric J.; Christison-Lagay, Emily R.; Sidebotham, Emma L.; Singer, Samuel; Antonescu, Cristina R.; Meyers, Paul A.; La Quaglia, Michael P.

    2012-01-01

    Purpose. Liposarcoma is extremely rare in the pediatric population. To identify prognostic factors and determine treatment outcomes, we reviewed our institutional experience with pediatric liposarcoma. Methods. We retrospectively reviewed all pediatric patients (age <22 years) with confirmed liposarcoma treated at Memorial Sloan-Kettering Cancer Center. Histologic subtype, tumor location, margin status, recurrence, and adjuvant therapy were analyzed and correlated with overall survival. Results. Thirty-four patients (56% male) with a median age of 18.1 years were identified. Twenty-two (65%) had peripheral tumors and 12 (35%) had centrally located tumors. Histologically, 29 (85%) tumors were low grade, and 5 (15%) were high grade pleomorphic. Eleven (32%) had recurrent disease, 9 patients with central tumors and 2 patients with peripheral lesions. Eight deaths occurred, all in patients with central disease. Five-year overall survival was 78%, with a median follow-up time of 5.4 years (range, 0.3–30.3 years). Tumor grade (P = .003), histologic subtype (P = .01), and primary location (P < .001) all correlated with survival, as did stage (P < .001) and margin status (P = .001). Conclusions. Central location of the primary tumor, high tumor grade, and positive surgical margins are strongly correlated with poor survival in pediatric patients with liposarcoma. PMID:22991488

  7. Prognostic factors of adult metastatic renal carcinoma: a multivariate analysis.

    PubMed

    de Forges, A; Rey, A; Klink, M; Ghosn, M; Kramar, A; Droz, J P

    1988-01-01

    In order to define the prognostic factors for metastatic renal carcinoma, we reviewed 134 patients who were treated from 1971 through 1986. Survival rates were 72, 45, and 25% at 6, 12, and 18 months, respectively. Seventeen variables were tested using the logrank test. Improved survival was correlated with normal performance status, and an absence of fever, weight loss, hepatic metastasis, and lung metastasis (or, if lung metastasis was present, less than 2 cm in diameter and limited to one site), a disease-free interval, sedimentation rate less than 100, and renal surgery. Four variables retained significant value in the multivariate analysis: hepatic metastasis, lung metastasis, disease-free interval, and a variable combining the sedimentation rate and the weight loss (SWRL). Predictive survival rates based on these variables were calculated from the Cox model. Six subgroups of patients were identified. The estimation of survival is clinically of value for future phase II trials of chemotherapy in patients with adult metastatic renal carcinoma. PMID:3187293

  8. Outcome and Prognostic Factors of Radiation Therapy for Medulloblastoma

    SciTech Connect

    Rieken, Stefan; Mohr, Angela; Habermehl, Daniel; Welzel, Thomas; Lindel, Katja; Witt, Olaf; Kulozik, Andreas E.; Wick, Wolfgang; Debus, Juergen; Combs, Stephanie E.

    2011-11-01

    Purpose: To investigate treatment outcome and prognostic factors after radiation therapy in patients with medulloblastomas (MB). Methods and Materials: Sixty-six patients with histologically confirmed MB were treated at University Hospital of Heidelberg between 1985 and 2009. Forty-two patients (64%) were pediatric ({<=}18 years), and 24 patients (36%) were adults. Tumor resection was performed in all patients and was complete in 47%. All patients underwent postoperative craniospinal irradiation (CSI) delivering a median craniospinal dose of 35.5 Gy with additional boosts to the posterior fossa up to 54.0 Gy. Forty-seven patients received chemotherapy, including 21 in whom chemotherapy was administered before CSI. Statistical analysis was performed using the log-rank test and the Kaplan-Meier method. Results: Median follow-up was 93 months. Overall survival (OS) and local and distant progression-free survival (LPFS and DPFS) were 73%, 62%, and 77% at 60 months. Both local and distant recurrence predisposed for significantly reduced OS. Macroscopic complete tumor resection, desmoplastic histology and early initiation of postoperative radiation therapy within 28 days were associated with improved outcome. The addition of chemotherapy did not improve survival rates. Toxicity was moderate. Conclusions: Complete resection of MB followed by CSI yields long survival rates in both children and adults. Delayed initiation of CSI is associated with poor outcome. Desmoplastic histology is associated with improved survival. The role of chemotherapy, especially in the adult population, must be further investigated in clinical studies.

  9. Clinical characteristics and prognostic factors of primary gastric lymphoma

    PubMed Central

    Wang, Yi-Gao; Zhao, Lin-Yong; Liu, Chuan-Qi; Pan, Si-Cheng; Chen, Xiao-Long; Liu, Kai; Zhang, Wei-Han; Yang, Kun; Chen, Xin-Zu; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Abstract Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma. This retrospective study aimed to analyze the clinical characteristics, prognostic factors, and roles of different treatment modalities in patients with PGL. From January 2003 to November 2014, 165 patients who were diagnosed with PGL at West China Hospital were enrolled in this study. The clinical features, treatment, and follow-up information were analyzed. In this study, diffuse large B-cell lymphoma (DLBCL) (108, 65.5%) and mucosa-associated lymphoid tissue (MALT) lymphoma (52, 31.5%) were two predominant histological subtypes. One-year and 5-year overall survival (OS) rates of all patients were 95.2% and 79.5%, respectively; in whom 110 (66.7%) underwent surgery, 110 (66.7%) received chemotherapy, 12 (7.3%) received radiotherapy, and 10 (6.1%) received Helicobacter pylori eradication. And 75 patients (45.5%) were treated with at least 2 different types of therapies. Elevated lactic dehydrogenase (LDH) levels, poor performance status (PS), advanced stage, International Prognostic Index (IPI) score ≥3, conservative treatment, and high-grade histological subtype were associated with worse prognosis in univariate analysis. Cox regression analysis showed that LDH levels, PS, staging, and histological subtype were independent predictors of survival outcomes. In the DLBCL type, 5-year OS was significantly better in the surgically treated group (80.1%) than that of patients conservatively treated (49.8%) (P = 0.001). Surgical treatment had almost no impact on OS in the MALT type than conservative treatment (P = 0.597). The proportion of patients received conservative treatment increased from 4.5% in period 1 to 51.7% in period 4. High LDH levels, poor PS, advanced staging, and malignant pathological type at diagnosis are significantly associated with poor OS. Our data suggest that surgery is superior in prognosis over conservative treatment in the DLBCL type, but not

  10. Prognostic correlation between MTA2 expression level and colorectal cancer

    PubMed Central

    Ding, Weijun; Hu, Wei; Yang, Haihua; Ying, Ting; Tian, Ye

    2015-01-01

    Objectives: Association of MTA2 expression with presence, development, metastasis and prognosis of colorectal cancer (CRC) was investigated. Methods: 90 CRC-related cases with follow-up information were made into tissue microarrays according to the paired principle of cancer tissues and the adjacent tissues. Subsequently, the expression of MAT2 was detected with immunohistochemical analysis and SPSS software was finally utilized to analyze the relationships between experimental data and clinical indicatives. Results: Expression of MTA2 in CRC tissues were notably higher than their adjacent tissues (P < 0.001) and showed significant positive correlation with tumor grade (r2 > 0, P < 0.01). Moreover, survival analysis indicated that MTA2 expression in cancer tissues, serving as an independent correlation factor, was significantly correlated with poor prognosis (P = 0.004). Conclusions: MTA2 is a crucial biomarker that is closely related with prognosis of CRC and also a potential molecular target for evaluating the prognosis and treatment of CRC. PMID:26261611

  11. Prognostic value of β1 integrin expression in colorectal liver metastases

    PubMed Central

    Vassos, Nikolaos; Rau, Tilman; Merkel, Susanne; Feiersinger, Fabian; Geppert, Carol I; Stürzl, Michael; Hohenberger, Werner; Croner, Roland S

    2014-01-01

    survival of patients, we showed that the β1 expression represents a reliable prognostic factor regarding the grading of liver metastases of CRC and our findings imply that β1 integrin expression profiles may have further potential in identifying the stage of colorectal liver metastases and being a marker of prognosis in these patients. PMID:24427350

  12. Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.

    PubMed Central

    Nakamura, M.; Katano, M.; Kuwahara, A.; Fujimoto, K.; Miyazaki, K.; Morisaki, T.; Mori, M.

    1998-01-01

    It has been generally accepted that transforming growth factor beta1 (TGF-beta1) has both negative and positive effects on tumour growth and progression. This study analysed the prognostic value of TGF-beta1 mRNA in advanced gastric carcinoma. A reverse transcriptase-polymerase chain reaction analysis (RT-PCR) was used for TGF-beta1 in endoscopic biopsy specimens from 42 advanced gastric carcinomas. Thirty specimens expressed TGF-beta1 mRNA while 12 specimens did not. The follow-up duration ranged from 4 to 37 months (mean 22.8 months). TGF-beta1-positive group demonstrated a shorter overall survival compared with the TGF-beta1 -negative group (P=0.0014). A significant correlation was also found in the 32 patients who underwent curative resection (P=0.0048). Significant correlations were found between TGF-beta1 mRNA expression and both stage (P=0.0015) and nodal involvement (P=0.0060). Multivariate analysis demonstrated that only TGF-beta1 mRNA expression (P=0.0306) was an independent prognostic factor. All of ten patients who underwent non-curative resection expressed TGF-beta1 mRNA. Expression of TGF-beta1 mRNA in gastric biopsy specimens may be an important preoperative prognostic variable for advanced gastric carcinoma. Images Figure 1 PMID:9823982

  13. Clinicopathological prognostic factors for upper tract urothelial carcinoma

    PubMed Central

    Timev, Alexander; Dimitrov, Plamen; Vasilev, Vasil; Krastanov, Alexander; Georgiev, Marincho; Yanev, Krasimir; Simeonov, Peter; Panchev, Peter

    2016-01-01

    Introduction The aim of the present study was to evaluate the influence of clinicopathological factors including age, gender, tumor grade, tumor stage, lymphovascular invasion (LVI), tumor necrosis and previous history of non-muscle invasive bladder cancer on outcomes of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Material and methods A total of 60 patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma at our institute between 2005 to 2012 were included in our study. Univariate and multivariate analysis was performed using the Kaplan-Meier method, log rank statistics, the chi-square test and Cox regression models. Results The mean length of follow-up time was 33.3 months. There were 27 (45%) patients alive with the disease, whereas 33 (55%) were dead. In 19 cases (31.7%) the tumor grade was low, while in 41 cases (68.3%) it was high. Lymphovascular invasion was observed in 28 (46.7%) cases. Tumor necrosis was registered in 14 patients (23.3%). From the patients with LVI, 3 (9.6%) were alive, whereas from the patients negative for LVI, 75% were alive. Significant relationship was found between gender and grading and between positive LVI and low grading. Conclusions Day case Variables such as gender, grading, tumor stage, LVI and tumor necrosis were all demonstrated to be significant independent prognostic factors for the overall survival. On the multivariate analysis only LVI remained statistically significant, which may explain the different clinical course in patients and could be considered as a part of pathological reporting and treatment planning for the future. PMID:27123328

  14. Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors

    PubMed Central

    Babu, Ranjith; Kranz, Peter G.; McLendon, Roger E.; Thomas, Steven; Friedman, Allan H.; Bigner, Darell D.; Adamson, Cory

    2015-01-01

    Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86–12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular characteristics which may aid in the treatment of these aggressive tumors. PMID:24838419

  15. The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients

    PubMed Central

    Grzybowska, Ewa Anna; Pienkowska-Grela, Barbara; Podgorska, Agnieszka; Zub, Renata; Olbryt, Magdalena; Pamula-Pilat, Jolanta; Lisowska, Katarzyna M.; Grzybowska, Ewa; Rubel, Tymon; Dansonka-Mieszkowska, Agnieszka; Konopka, Bozena; Kulesza, Magdalena; Lukasik, Martyna

    2015-01-01

    The CRNDE gene seems to play an oncogenic role in cancers, though its exact function remains unknown. Here, we tried to assess its usefulness as a molecular prognostic marker in ovarian cancer. Based on results of our microarray studies, CRNDE transcripts were further analyzed by Real-Time qPCR-based profiling of their expression. The qPCR study was conducted with the use of personally designed TaqMan assays on 135 frozen tissue sections of ovarian carcinomas from patients treated with platinum compounds and either cyclophosphamide (PC, N = 32) or taxanes (TP, N = 103). Elevated levels of two different CRNDE transcripts were a negative prognostic factor; they increased the risk of death and recurrence in the group of patients treated with TP, but not PC (DNA-damaging agents only). Higher associations were found for overexpression of the short CRNDE splice variant (FJ466686): HR 6.072, 95% CI 1.814–20.32, p = 0.003 (the risk of death); HR 15.53, 95% CI 3.812–63.28, p < 0.001 (the risk of recurrence). Additionally, accumulation of the TP53 protein correlated with decreased expression of both CRNDE transcripts in tumor cells. Our results depict CRNDE as a potential marker of poor prognosis in women with ovarian carcinomas, and suggest that its significance depends on the therapeutic regimen used. PMID:26556866

  16. Expression and Prognostic Value of Aquaporin 1, 3 in Cervical Carcinoma in Women of Uygur Ethnicity from Xinjiang, China

    PubMed Central

    Chen, Rui; Shi, Yonghua; Amiduo, Reshalaity; Tuokan, Talaf; Suzuk, Lalai

    2014-01-01

    Background Overexpression of several aquaporins has been reported in different types of human cancer but the role of aquaporins in carcinogenesis has not yet been clearly defined. There is few report concerning role of aquaporins in human cervical carcinogenesis so far. Here, we determined the expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in Chinese women of Uygur ethnicity. Methods and Results Real-time PCR analyses demonstrated aquaporin 1, 3 mRNA were differentially expressed in cervical carcinoma, CIN 2-3 and mild cervicitis. Immunofluorescent and immunohistochemical analyses demonstrated aquaporin 1 was predominantly localized to stromal endothelial cells in cervical lesions. Aquaporin 3 was localized to the membrane of normal squamous epithelium, CIN and carcinoma cells. Aquaporin 1 and 3 were upregulated in cervical cancer compared to mild cervicitis and CIN2-3 (P<0.05); Tumor expression of aquaporin 1, 3 significantly increased in advanced stage disease, and patients with deeper tumor infiltration, lymph node metastases or larger tumor volume (P<0.05). Multivariate analysis demonstrated that aquaporin 1, 3 were not independent prognostic factors in cervical carcinoma. Conclusion Aquaporins may participate in the initiation and progression of cervical carcinoma by promoting tumor growth, invasion or lymph node metastasis. Further study is required to determine whether aquaporins have potential as prognostic factors in cervical cancer. PMID:24918928

  17. Prognostic value of the IASLC/ATS/ERS classification and IMP3 expression in lung adenocarcinoma of Chinese cases

    PubMed Central

    Sun, Xiangjie; Wei, Ping; Shen, Chen; Yang, Yusi; Wang, Yiqin; Li, Yuan; Du, Xiang

    2015-01-01

    The IASLC/ATS/ERS classification system was proposed in 2011 to improve the histological subtypes of lung adenocarcinoma, while the prognostic value of the combination of histological predominant subtypes is not consistent. IMP3 is an oncofetal protein which has been proved associated with aggressive tumor behavior in malignancies, but few reports were investigated in lung adenocarcinoma. The aim of this study is to explore the prognostic value of the IASLC/ATS/ERS classification and IMP3 expression in lung adenocarcinoma of Chinese cases. A total of 196 cases were classified according to the IASLC/ATS/ERS classification system and immunohistochemically analyzed by using a monoclonal antibody against IMP3. Univariate survival analysis indicated patients with solid-predominant subtype had shorter disease-free survival (P = 0.003) and overall survival (P = 0.014) compared to those with non-solid predominant subtype. Multivariate survival analysis revealed that solid-predominant subtype could be an independent prognostic factor for disease-free survival (HR: 1.22, 95% CI: 1.05-1.41; P = 0.008). Analysis of IMP3 expression showed that IMP3 was more frequently overexpressed in tumors with advanced pTNM stage (P < 0.001), larger tumor size (P = 0.036), poorer histological differentiation (P < 0.001), lymph node metastasis (P < 0.001), and solid-predominant subtype (P < 0.001). Survival analysis also confirmed that patients in IMP3 high-expression group had both worse disease-free survival (P = 0.039) and overall survival (P = 0.029) than those in IMP3 low-expression group. Our results illustrated that solid-predominant subtype according to the IASLC/ATS/ERS classification is an independent prognostic factor, and IMP3 overexpression is associated with aggressive tumor behavior and poor clinical outcome in lung adenocarcinoma. PMID:26328257

  18. CCL21 as an independent favorable prognostic factor for stage III/IV colorectal cancer.

    PubMed

    Zou, Yifeng; Chen, Yufeng; Wu, Xianrui; Yuan, Ruixue; Cai, Zerong; He, Xiaosheng; Fan, Xinjuan; Wang, Lei; Wu, Xiaojian; Lan, Ping

    2013-08-01

    The aim of the present study was to investigate the expression dynamics of CCL21 and its prognostic significance in human stage III/IV colorectal cancer (CRC). CCL21 expression dynamics were detected with western blotting. The expression of CCL21 in CRC tissue microarrays was examined by immunohistochemistry. The optimal cut-point of CCL21 expression was assessed by the X-tile program. The prognostic significance was analyzed using both Kaplan-Meier curves and Cox regression analysis. Western blot analysis demonstrated that CCL21 expression was comparable in the CRC and normal colorectal tissues. According to the X-tile program, the cut-point for high expression of CCL21 in CRC was determined when the CCL21 expression index was >56.1. Overexpression of CCL21 was significantly correlated with larger tumor diameter, more mucinous carcinoma or signet ring cell carcinoma and poor tumor differentiation. Patients with high expression of CCL21 had a higher overall survival rate in comparison to patients with low expression. In the multivariate Cox regression analysis, CCL21 expression was found to be an independent prognostic biomarker for CRC. ROC curves showed that CCL21 expression could improve the prognostic capability of TNM stage in stage III/IV CRC patients. High expression of CCL21 is an independent and useful biomarker for predicting longer survival of stage III/IV CRC patients. PMID:23760102

  19. Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors.

    PubMed

    Moschetta, Marina Gobbe; Maschio, Larissa Bazela; Jardim-Perassi, Bruna Victorasso; Gelaleti, Gabriela Bottaro; Lopes, Juliana Ramos; Leonel, Camila; Gonçalves, Naiane Do Nascimento; Ferreira, Lívia Carvalho; Martins, Gustavo Rodrigues; Borin, Thaiz Ferraz; Zuccari, Debora Aparecida Pires De Campos

    2015-05-01

    Mammary tumors are the most common type of tumor in dogs, with approximately half of these tumors being malignant. Hypoxia, characterized by oxygen levels below normal, is a known adverse factor to cancer treatment. The hypoxia-inducible factor 1α (HIF-1α) is a central regulator of the pathophysiological response of mammalian cells to low oxygen levels. HIF-1α activates the transcription of vascular endothelial growth factor (VEGF), which in turn promotes angiogenesis through its ability to stimulate the growth, migration and invasion of endothelial cells to form new blood vessels, contributing to tumor progression. In this study, we evaluated the serum concentration and gene expression of VEGF and HIF-1α linking them with clinicopathological parameters and survival of dogs with mammary tumors in order to infer the possible prognostic value of these factors. We collected blood and tumor fragments of 24 female dogs with malignant mammary tumors (study group) and 26 non-affected female dogs (control group) to verify the gene expression of VEGF and HIF-1α by quantitative real-time PCR (qPCR) and the serum levels by ELISA (enzyme-linked immunosorbent). The results showed high serum levels of VEGF in the study group and its correlation between abundant vascularization, lymph node involvement, metastasis, death rate and low survival (p<0.05). The serum percentage of HIF-1α in female dogs with mammary neoplasia was lower than that in the control group and higher in female dogs with tumor metastasis and history of tumor recurrence (p<0.05). Regarding gene expression, there was a gene overexpression of VEGFA in female dogs with poor outcome, in contrast to the gene underexpression of HIF-1A. Taken together, these results suggested that VEGF is important in tumor progression and can be used as a potential prognostic marker in the clinic and may be useful in predicting tumor progression in dogs with mammary neoplasia. PMID:25779537

  20. Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer.

    PubMed

    Rodrigues, P R S; Maia, L L; Santos, M; Peterle, G T; Alves, L U; Takamori, J T; Souza, R P; Barbosa, W M; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-01-01

    The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies. PMID:26634459

  1. Prognostic factors of laryngeal solitary extramedullary plasmacytoma: a case report and review of literature

    PubMed Central

    Xing, Yong; Qiu, Jun; Zhou, Min-Li; Zhou, Shui-Hong; Bao, Yang-Yang; Wang, Qin-Ying; Zheng, Zhou-Jun

    2015-01-01

    A paucity of data exists concerning the presentation, natural course and outcome of extramedullary plasmcytoma (EMP). It is difficult to determine the optimal treatment strategy and prognostic factors for EMP. We present an additional case of laryngeal EMP and systemic review relevant reports in the English and Chinese literature. We found, to our knowledge, 147 cases in larynx in the English-language literature and Chinese-literature. The most common treatment modality was radiotherapy alone. The mean survival duration was ~184 months, and the 5- and 10- year survival rates were 76.1% and 67.4%, respectively. The univariate analysis suggested that progression to multiple myeloma and amyloid deposits may be poor prognostic factors. The multivariate analysis suggested that only progression to multiple myeloma may be a poor prognostic factor. Laryngeal EMP is uncommon. Progression to multiple myeloma may be a poor prognostic factor. PMID:26045749

  2. Prognostic Factors in Myoepithelial Carcinoma of Salivary Glands

    PubMed Central

    Kong, Max; Drill, Esther N.; Morris, Luc; West, Lyndsay; Klimstra, David; Gonen, Mithat; Ghossein, Ronald; Katabi, Nora

    2016-01-01

    Myoepithelial carcinoma (MECA) is an underrecognized rare tumor with a diverse clinical behavior. The histologic features of this tumor are not well characterized, much less its grading, which is controversial. The objective of this study is to provide a better characterization of MECA and its prognostic factors. A total of 48 cases were retrieved from the pathology files. The cases were subjected to a detailed histopathologic, immunohistochemical, statistical, and clinical analysis. Tumors were classified as de novo MECA in 22 cases (46%) and carcinoma ex-pleomorphic adenoma (CA ex-PA) in 26 cases (54%). Tumor necrosis, high mitotic count (≥6/10 high-power fields), and severe pleomorphism were identified in 38%, 33%, and 21%, respectively. Perineural invasion, vascular invasion, and positive margins were noted in 10%, 12%, and 47%, respectively. Median follow-up was 38 months. Four patients had lymph node metastasis at presentation, 9 developed local recurrences, and 12 had distant metastases with the lung being the most common site (83%). The presence of CA ex-PA, necrosis, and vascular invasion correlated significantly with disease-free survival (P = 0.02, 0.01, 0.03, respectively). No distant recurrence was noted in all 23 patients lacking necrosis in their neoplasms (median follow-up: 44 mo). MECA is a relatively aggressive tumor that is associated with a high rate of distant metastasis (27%). Compared with de novo MECA, CA ex-PA correlates with worse clinical outcome. A grading system based on the presence of tumor necrosis should be used to identify high-grade MECA and predict its clinical behavior. PMID:25970687

  3. Prognostic Significance of EBV Latent Membrane Protein 1 Expression in Lymphomas: Evidence from 15 Studies

    PubMed Central

    Mao, Yuan; Lu, Mei Ping; Lin, Hong; Zhang, Da Wei; Liu, Ying; Li, Qing Dong; Lv, Zhi Gang; Xu, Jia Ren; Chen, Ren Jie; Zhu, Jin

    2013-01-01

    Background Epstein-Barr virus (EBV) infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma. Methods The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR) and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival. Results Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92–1.68]). In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL) (HR  = 1.84, 95% CI: 1.02–3.34), but not with survival of patients with Hodgkin disease (HD) (HR  =  1.03, 95% CI: 0.74–1.44). In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value. Conclusions This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression. PMID:23613723

  4. Human mutL homolog 1 expression characteristic and prognostic effect on patients with sporadic colorectal cancer

    PubMed Central

    Pu, Chibin; Ren, Weiguo; Sun, Zhenqiang; Yu, Xianbo; Yuan, Wei; Huang, Mingyu; Shen, Shourong; Wang, Xiaoyan

    2015-01-01

    The aim of the present study was to analyze the relationship between aberrant human mutL homolog 1 (hMLH1) expression and clinicopathological parameters of patients with sporadic colorectal cancer, and to explore the prognostic effect of aberrant hMLH1 expression in these patients. The relationship was measured by chi-square test and Fisher’s exact test. Survival analysis was performed with Kaplan-Meier analysis and Cox regression model to measure 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates. Totally 17.13% of the patients with sporadic colorectal cancer showed aberrant nuclear staining for hMLH1 expression. Aberrant hMLH1 expression was related with tumor pathologic types, tumor location and TNM staging (P<0.05) in the patients with sporadic colorectal cancer. Cox regression analysis indicated important prognostic factors were age (RR: 1.021, 95% CI: 1.003-1.039, P=0.023), mucinous adenocarcinoma (RR: 2.603, 95% CI: 1.705-3.974, P<0.0001), TNM staging (RR: 2.071, 95% CI: 1.170-3.666, P=0.012), lymphangion invasion (RR: 2.013, 95% CI: 1.227-3.303, P=0.006) and aberrant hMLH1 expression (RR: 0.414, 95% CI: 0.216-0.791, P=0.008). Consequently, hMLH1 expression level is related with some clinicopathologic features. Aberrant hMLH1 expression plays a significant part in prognosis for patients with sporadic colorectal cancer and it will promisingly become an independent prognostic factor. PMID:26770629

  5. Role and prognostic significance of the epithelial-mesenchymal transition factor ZEB2 in ovarian cancer

    PubMed Central

    Prislei, Silvia; Martinelli, Enrica; Zannoni, Gian Franco; Petrillo, Marco; Filippetti, Flavia; Mariani, Marisa; Mozzetti, Simona; Raspaglio, Giuseppina; Scambia, Giovanni; Ferlini, Cristiano

    2015-01-01

    ZEB2 is a key factor in epithelial-mesenchymal transition (EMT), a program controlling cell migration in embryonic development and adult tissue homeostasis. We demonstrated a role of ZEB2 in migration and anchorage-independent cell growth in ovarian cancer, as shown by ZEB2 silencing. We found that the RNA-binding protein HuR bound the 3′UTR of ZEB2 mRNA, acting as a positive regulator of ZEB2 protein expression. In Hey ovarian cell line, HuR silencing decreased ZEB2 and ZEB1 nuclear expression and impaired migration. In hypoglycemic conditions ZEB2 expression decreased, along with ZEB1, vimentin and cytoplasmic HuR, and a reduced cellular migration ability was observed. Analysis of ZEB2 and HuR expression in ovarian cancers revealed that nuclear ZEB2 is localized in tumor leading edge and co-localizes with cytoplasmic HuR. In a series of 143 ovarian cancer patients high expression of ZEB2 mRNA significantly correlated with a poor prognosis in term of both overall survival and progression- free survival. Moreover, at immunohistochemical evaluation, we found that prognostic significance of ZEB2 protein relies on its nuclear expression and co-localization with cytoplasmic HuR. In conclusion our findings indicated that nuclear ZEB2 may enhance progression of EMT transition and acquisition of an aggressive phenotype in ovarian cancer. PMID:26136338

  6. Prognostic Factors of Primary Intraosseous Squamous Cell Carcinoma (PIOSCC): A Retrospective Review

    PubMed Central

    Wenguang, Xu; Hao, Shen; Xiaofeng, Qi; Zhiyong, Wang; Yufeng, Wang; Qingang, Hu; Wei, Han

    2016-01-01

    Objectives To delineate clinical and pathological features and determine the prognostic factors of primary intraosseous squamous cell carcinoma (PIOSCC). Materials and methods Patients diagnosed with PIOSCC, attending the department of oral and maxillofacial surgery, Nanjing stomatological hospital between 2005 and 2015, were identified and retrospectively reviewed for clinical and pathological characteristics. Therapeutic modalities were measured and related follow-up data recorded, in order to determine prognostic factors of PIOSSC. Results A total of 77 patients with PIOSCC were included in the study. Mean age at diagnosis was 58.8 years, (range, 37−81 years). Of the 77 patients, there were 58 men and 19 women. The most common location of disease was the mandible (71.42%), particularly the posterior mandible. The common presenting symptoms included jaw swelling (79.2%) and ulceration (42.65%). The estimated 2-year and 5-year overall survival were 68.9% and 38.8%, respectively. Univariate analysis identified the following as negative prognostic factors: histological grade, N classification, nodal status and treatment modalities. However, multivariate analysis determined positive nodal status, high histological grade and advanced N classification as the independent significant prognostic factors. Conclusion Our results demonstrate several clinical and pathological features of PIOSCC and identify important prognostic factors associated with overall survival in PIOSCC. These prognostic factors include nodal status, histological grade, N classification, and treatment modalities, all of which are important for patient counseling and may be useful for the development of new treatment approaches. PMID:27074366

  7. Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer

    PubMed Central

    Becker, Marc A.; Ibrahim, Yasir H.; Oh, Annabell S.; Fagan, Dedra H.; Byron, Sara A.; Sarver, Aaron L.; Lee, Adrian V.; Shaw, Leslie M.; Fan, Cheng; Perou, Charles M.; Yee, Douglas

    2016-01-01

    Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer. PMID:26991655

  8. [Retrospective analysis of prognostic factors in patients with primary lymphoma of the intestine].

    PubMed

    Avilés, A; Guzmán, R; Huerta, J; Díaz-Maqueo, J C

    1991-01-01

    Forty-six patients with stage IE and IIE malignant lymphoma of the intestine were analyzed to assess the efficacy of prognostic factors to predict the course and therapeutic approach in these patients. Because the lesion was considered unresectable in all cases, chemotherapy was given after surgery. Using Cox's univariate regression analysis, survival was found to correlate with stage (IE vs IIE) and high levels of lactic dehidrogenase, nevertheless in the multivariate analysis only beta 2 microglobulin levels were associated with a shorter survival. We believe that treatment of extranodal lymphomas, like nodal presentations, as those of the intestine, could be based in the determinations of prognostic factors and that beta 2 microglobulin would be considered the most powerful prognostic factor. Most studies on patients with malignant lymphoma of the intestine are necessary to define the role of beta 2 microglobulin as therapeutic prognostic index. PMID:1810010

  9. Prognostic value of peritumoral heat-shock factor-1 in patients receiving resection of hepatocellular carcinoma

    PubMed Central

    Zhang, J-B; Guo, K; Sun, H-C; Zhu, X-D; Zhang, B; Lin, Z-H; Zhang, B-H; Liu, Y-K; Ren, Z-G; Fan, J

    2013-01-01

    Background: The cross-talk of hepatocellular carcinoma (HCC) cells and abnormal metabolic signals in peritumoral microenvironment modifies our knowledge of hepatocarcinogenesis. As an indispensable modulator of various stresses, the clinical significance of heat-shock transcription factor-1 (HSF1) in HCC microenvironment has never been defined. Methods: Hepatocellular carcinoma and matched peritumoral liver tissues (n=332) were semiquantitatively analysed for HSF1 expression, followed by correlation with clinicopathological parameters (patient outcomes). Moreover, the effects of HSF1 deficiency in L02 on monocarboxylate transporter-4 (MCT4) and HCC cells' colonisation and proliferation were investigated. Results: High expression of HSF1 in peritumoral tissue but not in HCC tissue was associated with poorer overall survival (OS) and time to recurrence (TTR), especially early recurrence (ER), which was further reconfirmed in validation cohort. Multivariate analysis showed that prognostic performance of peritumoral HSF1 was independent of other clinicopathological factors (hazard ratio for OS=2.60, P=0.002, for TTR=2.52, P<0.001). Notably, downregulation of HSF1 in L02 decreased MCT4 expression significantly. The supernatant from L02-shRNA-HSF1 in hypoxia, NOT normoxia condition, inhibited HCC cell colonisation and proliferation. Moreover, the combination of peritumoral HSF1 and MCT4 was the best predictor for ER and OS. Conclusion: High peritumoral HSF1 expression can serve as a sensitive ‘readout' for high-risk HCC ER, and could be a potential metabolic intervention target following curative resection. PMID:24002609

  10. Growth arrest DNA damage-inducible gene 45 gamma expression as a prognostic and predictive biomarker in hepatocellular carcinoma

    PubMed Central

    Ou, Da-Liang; Shyue, Song-Kun; Lin, Liang-In; Feng, Zi-Rui; Liou, Jun-Yang; Fan, Hsiang-Hsuan; Lee, Bin-Shyun; Hsu, Chiun; Cheng, Ann-Lii

    2015-01-01

    Growth arrest DNA damage-inducible gene 45 (GADD45) family proteins play a crucial role in regulating cellular stress responses and apoptosis. The present study explored the prognostic and predictive role of GADD45γ in hepatocellular carcinoma (HCC) treatment. GADD45γ expression in HCC cells was examined using quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. The control of GADD45γ transcription was examined using a luciferase reporter assay and chromatin immunoprecipitation. The in vivo induction of GADD45γ was performed using adenoviral transfer. The expression of GADD45γ in HCC tumor tissues from patients who had undergone curative resection was measured using qRT-PCR. Sorafenib induced expression of GADD45γ mRNA and protein, independent of its RAF kinase inhibitor activity. GADD45γ induction was more prominent in sorafenib-sensitive HCC cells (Huh-7 and HepG2, IC50 6–7 μM) than in sorafenib-resistant HCC cells (Hep3B, Huh-7R, and HepG2R, IC50 12–15 μM). Overexpression of GADD45γ reversed sorafenib resistance in vitro and in vivo, whereas GADD45γ expression knockdown by using siRNA partially abrogated the proapoptotic effects of sorafenib on sorafenib-sensitive cells. Overexpression of survivin in HCC cells abolished the antitumor enhancement between GADD45γ overexpression and sorafenib treatment, suggesting that survivin is a crucial mediator of antitumor effects of GADD45γ. GADD45γ expression decreased in tumors from patients with HCC who had undergone curative surgery, and low GADD45γ expression was an independent prognostic factor for poor survival, in addition to old age and vascular invasion. The preceding data indicate that GADD45γ suppression is a poor prognostic factor in patients with HCC and may help predict sorafenib efficacy in HCC. PMID:26172295

  11. The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.

    PubMed

    Cho, Soo Youn; Ha, Sang Yun; Huang, Song-Mei; Kim, Jeong Hoon; Kang, Myung Soo; Yoo, Hae-Yong; Kim, Hyeon-ho; Park, Cheol-Keun; Um, Sung-Hee; Kim, Kyung-Hee; Kim, Seok-Hyung

    2014-11-01

    Smad3 functions as an integrator of diverse signaling, including transforming growth factor β signaling and the function of Smad3 is complexly regulated by differential phosphorylation at various sites of Smad3. Despite the importance of Smad3 and its various phosphoisoforms, their prognostic significance has rarely been studied. In this study, we demonstrated the prognostic significance of Smad3, its phosphoisoforms, and Smad4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas. The phosphoisoforms of Smad3 studied in this article included phosphorylation at C-terminal (pSmad3C)(Ser(423/425)) and phosphorylation at the linker region (pSmad3L)(Ser(213)). High expression of Smad3 was associated with shorter overall survival. Co-existence of high expression of pSmad3L(S213) and low expression of pSmad3C(S423/425) were associated with advanced N stage and an independent prognostic factor for overall [hazard ratio (HR) 2.03, 95 % confidence interval (CI) (1.10-3.75), p = 0.023] and disease-free survival [HR 2.41, 95 % CI (1.32-4.39), p = 0.004]. In conclusion, co-existence of high pSmad3L(Ser(213)) expression and low pSmad3C(Ser(423/425)) expression can be considered as immunohistochemical biomarkers for predicting prognosis as well as future therapeutic targets. In addition, our results of combinatory effect of differential phosphorylation of Smad3 on prognosis suggest the mode of action of Smad3 might be logically determined by its phosphorylation pattern. PMID:25267569

  12. Prognostic significance of XIAP expression in DLBCL and effect of its inhibition on AKT signalling.

    PubMed

    Hussain, Azhar R; Uddin, Shahab; Ahmed, Maqbool; Bu, Rong; Ahmed, Saeeda O; Abubaker, Jehad; Sultana, Mehar; Ajarim, Dahish; Al-Dayel, Fouad; Bavi, Prashant P; Al-Kuraya, Khawla S

    2010-10-01

    The inhibitor of apoptosis protein (IAP) family member X-linked inhibitor of apoptosis protein (XIAP) is essential for cell survival in lymphoma. However, the role of XIAP overexpression in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Therefore, we analysed the expression of XIAP protein and its clinicopathological correlation in a large cohort of DLBCLs by immunohistochemistry in a tissue micro-array format. XIAP was found to be overexpressed in 55% of DLBCLs and significantly associated with poor clinical outcome (p = 0.0421). To further elucidate the role of XIAP in DLBCL and the inter-relationship with PI3-kinase/AKT signalling, we conducted several in vitro studies using a panel of DLBCL cell lines. We found that pharmacological inhibition of XIAP led to caspase-dependent apoptosis in DLBCL cells. We also detected an inter-relationship between XIAP expression and activated AKT in DLBCL cells that may explain cellular resistance to PI3-kinase/AKT inhibition-mediated apoptosis. Finally, this anti-apoptotic effect was overcome by simultaneous pharmacological inhibition of XIAP and PI3-kinase/AKT signalling leading to a more potent synergistically induced apoptosis. In summary, our data suggest that XIAP expression is a poor prognostic factor in DLBCL and the XIAP-AKT relationship should be explored further as a potential therapeutic target in DLBCL. PMID:20632385

  13. Prognostic factors of whiplash-associated disorders: a systematic review of prospective cohort studies.

    PubMed

    Scholten-Peeters, Gwendolijne G M; Verhagen, Arianne P; Bekkering, Geertruida E; van der Windt, Daniëlle A W M; Barnsley, Les; Oostendorp, Rob A B; Hendriks, Erik J M

    2003-07-01

    We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e

  14. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-06-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells

  15. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    SciTech Connect

    Mestre, Francisco; Gutiérrez, Antonio; Rodriguez, Jose; Ramos, Rafael; Garcia, Juan Fernando; Martinez-Serra, Jordi; Casasus, Marta; Nicolau, Cristina; Bento, Leyre; Herraez, Ines; Lopez-Perezagua, Paloma; Daumal, Jaime; Besalduch, Joan

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  16. Gene expression of INPP5F as an independent prognostic marker in fludarabine-based therapy of chronic lymphocytic leukemia

    PubMed Central

    Palermo, G; Maisel, D; Barrett, M; Smith, H; Duchateau-Nguyen, G; Nguyen, T; Yeh, R-F; Dufour, A; Robak, T; Dornan, D; Weisser, M

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes (n=237; discovery set) and peripheral blood mononuclear cells (n=92; validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F (INPP5F) as a prognostic factor for progression-free survival (P<0.001; hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.35–1.98) and overall survival (P<0.001; HR, 1.47; 95% CI, 1.18–1.84), regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL. PMID:26430724

  17. Prognostic Significance of Vascular Endothelial Growth Factor Serum Determination in Women with Ovarian Cancer

    PubMed Central

    Bandiera, Elisabetta; Franceschini, Roberta; Specchia, Claudia; Bignotti, Eliana; Trevisiol, Chiara; Gion, Massimo; Pecorelli, Sergio; Santin, Alessandro Davide; Ravaggi, Antonella

    2012-01-01

    Introduction. We performed a review of the literature to elucidate the potential prognostic significance of serum vascular endothelial growth factor (sVEGF) levels in ovarian cancer. Methods. Eligible studies in English and Italian were identified in MEDLINE/PubMed from VEGF discovery to October 2011. All studies evaluating: (i) sVEGF levels before any surgical and chemotherapeutic treatment; (ii) the association between sVEGF levels and the established prognostic variables; (iii) the value of sVEGF levels in predicting patients' outcomes, were selected for this review. Results. The search resulted in 758 titles. Nine studies met the inclusion criteria. A statistically significant association between the level of sVEGF and FIGO stage, tumour grade, residual tumour size, lymph node involvement, and presence of ascites was found in at least one study. sVEGF, in comparison with the established prognostic factors, appears to be the best prognostic marker for overall survival, since it stands out as an independent prognostic factor in most of the studies considered. Moreover, sVEGF levels were shown to be independent prognostic factors by 2 out of the 3 studies that considered DFS as an end point. Conclusion. High levels of sVEGF identify a subgroup of patients with higher risk of death and/or recurrence. These patients should be eligible for individually tailored therapeutic interventions. PMID:22792477

  18. Prognostic Factors of Hepatosplenic T-cell Lymphoma: Clinicopathologic Study of 28 Cases.

    PubMed

    Yabe, Mariko; Medeiros, L Jeffrey; Tang, Guilin; Wang, Sa A; Ahmed, Sairah; Nieto, Yago; Hu, Shimin; Bhagat, Govind; Oki, Yasuhiro; Patel, Keyur P; Routbort, Mark; Luthra, Rajyalakshmi; Fanale, Michelle A; Bueso-Ramos, Carlos E; Jorgensen, Jeffrey L; Vega, Francisco; Chen, Weina; Hoehn, Daniela; Konoplev, Sergej; Milton, Denai R; Wistuba, Ignacio; Li, Shaoying; You, M James; Young, Ken H; Miranda, Roberto N

    2016-05-01

    Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αβ TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αβ TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than any other. However, patients who underwent stem cell transplant showed longer survival (OS: hazard ratio 0.3, P=0.09; EFS: hazard ratio 0.2, P=0.034). In conclusion, although HSTCL patients have a poor prognosis overall, the data presented support the novel suggestions that HSTCL patients can be stratified into 2 prognostic groups, with an elevated serum bilirubin level, αβ TCR expression, and trisomy 8 identifying a poorer prognostic group. In addition, the outcomes of this patient cohort suggest that stem cell transplantation has value for the treatment of patients with HSTCL. PMID:26872013

  19. Course and Prognostic Factors for Neck Pain in the General Population

    PubMed Central

    Hogg-Johnson, Sheilah; van der Velde, Gabrielle; Haldeman, Scott; Holm, Lena W.; Carragee, Eugene J.; Hurwitz, Eric L.; Côté, Pierre; Nordin, Margareta; Peloso, Paul M.; Guzman, Jaime; Cassidy, J. David

    2008-01-01

    Study Design Best evidence synthesis. Objective To undertake a best evidence synthesis on course and prognosis of neck pain and its associated disorders in the general population. Summary of Background Data Knowing the course of neck pain guides expectations for recovery. Identifying prognostic factors assists in planning public policies, formulating interventions, and promoting lifestyle changes to decrease the burden of neck pain. Methods The Bone and Joint Decade 2000 –2010 Task Force on Neck Pain and its Associated Disorders (Neck Pain Task Force) conducted a critical review of literature published between 1980 and 2006 to assemble the best evidence on neck pain. Findings fromstudiesmeeting criteria for scientific validity were abstracted into evidence tables and included in a best evidence synthesis. Results We found 226 articles on the course and prognostic factors in neck pain and its associated disorders. After critical review, 70 (31) of these were accepted on scientific merit. Six studies related to course and 7 to prognostic factors in the general population. Between half and three quarters of persons in these populations with current neck pain will report neck pain again 1 to 5 years later. Younger age predicted better outcome. General exercise was unassociated with outcome, although regular bicycling predicted poor outcome in 1 study. Psychosocial factors, including psychologic health, coping patterns, and need to socialize, were the strongest prognostic factors. Several potential prognostic factors have not been well studied, including degenerative changes, genetic factors, and compensation policies. Conclusion The Neck Pain Task Force undertook a best evidence synthesis to establish a baseline of the current best evidence on the course and prognosis for this symptom. General exercise was not prognostic of better outcome; however, several psychosocial factors were prognostic of outcome.

  20. Methylator phenotype in colorectal cancer: A prognostic factor or not?

    PubMed

    Gallois, C; Laurent-Puig, P; Taieb, J

    2016-03-01

    Colorectal cancer (CRC) is due to different types of genetic alterations that are translated into different phenotypes. Among them, CpG island methylator phenotype (CIMP+) is the most recently involved in carcinogenesis of some CRC. The malignant transformation in this case is mainly due to the transcriptional inactivation of tumor suppressor genes. CIMP+ are reported to be more frequently found in the elderly and in women. The tumors are more frequently located in the proximal part of the colon, BRAF mutated and are associated with microsatellite instability (MSI) phenotype. All sporadic MSI CRC belong to the methylator phenotype, however some non MSI CRC may also harbor a methylator phenotype. The prognostic value of CIMP is not well known. Most studies show a worse prognosis in CIMP+ CRC, and adjuvant treatments seem to be more efficient. We review here the current knowledge on prognostic and predictive values in CIMP+ CRC. PMID:26702883

  1. LTPB2 acts as a prognostic factor and promotes progression of cervical adenocarcinoma

    PubMed Central

    Ren, Yuan; Lu, Huan; Zhao, Danmei; Ou, Yangjun; Yu, Kang; Gu, Jiandong; Wang, Li; Jiang, Shuheng; Chen, Mo; Wang, Jinghao; Zhang, Rong; Xu, Congjian

    2015-01-01

    Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) is a member of the fibrillin/LTBP super family of extracellular matrix proteins, found to be overexpressed in certain malignant tumors. However, the clinical significance and biological role of LTBP-2 in cervical adenocarcinoma has remains unclear. We found that the expression of LTBP2 was higher in cervical adenocarcinoma than in normal cervical epithelial tissue as assessed by immunohistochemistry. Expression of LTBP2 is related to clinical stage, cervical tumor size, depth of cervical stromal invasion and lymph node metastasis. Knockdown of LTBP2 expression can inhibit the proliferation and migration of HeLa cells. Moreover, LTBP2 knockdown affected multiple tumor-related pathway genes including: the MAPK signaling pathway, the PI3K-AKT signaling pathway, receptor tyrosine kinase signaling and the P53 pathway. Taken together, this work suggests that LTBP2 may promote the development of cervical adenocarcinoma and serve as a prognostic factor in the clinical evaluation of patients with cervical adenocarcinoma. Our findings provide a new strategy for the diagnosis and treatment of cervical adenocarcinoma. PMID:26279753

  2. The Prognostic and Predictive Role of Epidermal Growth Factor Receptor in Surgical Resected Pancreatic Cancer.

    PubMed

    Guo, Meng; Luo, Guopei; Liu, Chen; Cheng, He; Lu, Yu; Jin, Kaizhou; Liu, Zuqiang; Long, Jiang; Liu, Liang; Xu, Jin; Huang, Dan; Ni, Quanxing; Yu, Xianjun

    2016-01-01

    The data regarding the prognostic significance of EGFR (epidermal growth factor receptor) expression and adjuvant therapy in patients with resected pancreatic cancer are insufficient. We retrospectively investigated EGFR status in 357 resected PDAC (pancreatic duct adenocarcinoma) patients using tissue immunohistochemistry and validated the possible role of EGFR expression in predicting prognosis. The analysis was based on excluding the multiple confounding parameters. A negative association was found between overall EGFR status and postoperative survival (p = 0.986). Remarkably, adjuvant chemotherapy and radiotherapy were significantly associated with favorable postoperative survival, which prolonged median overall survival (OS) for 5.8 and 10.2 months (p = 0.009 and p = 0.006, respectively). Kaplan-Meier analysis showed that adjuvant chemotherapy correlated with an obvious survival benefit in the EGFR-positive subgroup rather than in the EGFR-negative subgroup. In the subgroup analyses, chemotherapy was highly associated with increased postoperative survival in the EGFR-negative subgroup (p = 0.002), and radiotherapy had a significant survival benefit in the EGFR-positive subgroup (p = 0.029). This study demonstrated that EGFR expression is not correlated with outcome in resected pancreatic cancer patients. Adjuvant chemotherapy and radiotherapy were significantly associated with improved survival in contrary EGFR expressing subgroup. Further studies of EGFR as a potential target for pancreatic cancer treatment are warranted. PMID:27399694

  3. The Prognostic and Predictive Role of Epidermal Growth Factor Receptor in Surgical Resected Pancreatic Cancer

    PubMed Central

    Guo, Meng; Luo, Guopei; Liu, Chen; Cheng, He; Lu, Yu; Jin, Kaizhou; Liu, Zuqiang; Long, Jiang; Liu, Liang; Xu, Jin; Huang, Dan; Ni, Quanxing; Yu, Xianjun

    2016-01-01

    The data regarding the prognostic significance of EGFR (epidermal growth factor receptor) expression and adjuvant therapy in patients with resected pancreatic cancer are insufficient. We retrospectively investigated EGFR status in 357 resected PDAC (pancreatic duct adenocarcinoma) patients using tissue immunohistochemistry and validated the possible role of EGFR expression in predicting prognosis. The analysis was based on excluding the multiple confounding parameters. A negative association was found between overall EGFR status and postoperative survival (p = 0.986). Remarkably, adjuvant chemotherapy and radiotherapy were significantly associated with favorable postoperative survival, which prolonged median overall survival (OS) for 5.8 and 10.2 months (p = 0.009 and p = 0.006, respectively). Kaplan–Meier analysis showed that adjuvant chemotherapy correlated with an obvious survival benefit in the EGFR-positive subgroup rather than in the EGFR-negative subgroup. In the subgroup analyses, chemotherapy was highly associated with increased postoperative survival in the EGFR-positive subgroup (p = 0.002), and radiotherapy had a significant survival benefit in the EGFR-negative subgroup (p = 0.029). This study demonstrated that EGFR expression is not correlated with outcome in resected pancreatic cancer patients. Adjuvant chemotherapy and radiotherapy were significantly associated with improved survival in contrary EGFR expressing subgroup. Further studies of EGFR as a potential target for pancreatic cancer treatment are warranted. PMID:27399694

  4. Course and Prognostic Factors for Neck Pain in Whiplash-Associated Disorders (WAD)

    PubMed Central

    Holm, Lena W.; Hogg-Johnson, Sheilah; Côté, Pierre; Cassidy, J. David; Haldeman, Scott; Nordin, Margareta; Hurwitz, Eric L.; Carragee, Eugene J.; van der Velde, Gabrielle; Peloso, Paul M.; Guzman, Jaime

    2008-01-01

    Study Design Best evidence synthesis. Objective To perform a best evidence synthesis on the course and prognostic factors for neck pain and its associated disorders in Grades I–III whiplash-associated disorders (WAD). Summary of Background Data Knowledge of the course of recovery of WAD guides expectations for recovery. Identifying prognostic factors assists in planning management and intervention strategies and effective compensation policies to decrease the burden of WAD. Methods The Bone and Joint Decade 2000–2010 Task Force on Neck Pain and its Associated Disorders (Neck Pain Task Force) conducted a critical review of the literature published between 1980 and 2006 to assemble the best evidence on neck pain and its associated disorders. Studies meeting criteria for scientific validity were included in a best evidence synthesis. Results We found 226 articles related to course and prognostic factors in neck pain and its associated disorders. After a critical review, 70 (31%) were accepted on scientific merit; 47 of these studies related to course and prognostic factors in WAD. The evidence suggests that approximately 50% of those with WAD will report neck pain symptoms 1 year after their injuries. Greater initial pain, more symptoms, and greater initial disability predicted slower recovery. Few factors related to the collision itself (for example, direction of the collision, headrest type) were prognostic; however, postinjury psychological factors such as passive coping style, depressed mood, and fear of movement were prognostic for slower or less complete recovery. There is also preliminary evidence that the prevailing compensation system is prognostic for recovery in WAD. Conclusion The Neck Pain Task Force undertook a best evidence synthesis to establish a baseline of the current best evidence on the course and prognosis for WAD. Recovery of WAD seems to be multifactorial.

  5. Prognostic and Predictive Value of Baseline and Posttreatment Molecular Marker Expression in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy

    SciTech Connect

    Bertolini, Federica . E-mail: bertolini.federica@policlinico.mo.it; Bengala, Carmelo; Losi, Luisa; Pagano, Maria; Iachetta, Francesco; Dealis, Cristina; Jovic, Gordana; Depenni, Roberta; Zironi, Sandra; Falchi, Anna Maria; Luppi, Gabriele; Conte, Pier Franco

    2007-08-01

    Purpose: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. Methods and Materials: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. Results: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. Conclusions: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer.

  6. A new prognostic index to make short-term prognoses in MDS patients treated with azacitidine: A combination of p53 expression and cytogenetics.

    PubMed

    Nishiwaki, Satoshi; Ito, Masafumi; Watarai, Rie; Okuno, Shingo; Harada, Yasuhiko; Yamamoto, Satomi; Suzuki, Kotaro; Kurahashi, Shingo; Iwasaki, Toshihiro; Sugiura, Isamu

    2016-02-01

    TP53 mutation is associated with various hematological malignancies and immunohistochemistry of p53 has been used as a simple method to establish the presence of a TP53 mutation. Since the significance of p53 expression is controversial in myelodysplastic syndrome (MDS) patients treated with azacitidine (Aza), we analyzed the prevalence of p53 expression as a prognostic factor in 60 MDS patients treated with Aza. To assess p53 expression, immunohistochemical analyses of bone marrow clot sections were performed. Overall survival (OS) was significantly lower in p53-positive patients compared with p53-negetive patients (59% vs. 85% at 12 months; P=0.006). Multivariate analysis demonstrated that p53-positive was a significant prognostic factor for OS along with poor cytogenetics. Here, we propose a new prognostic index to make short-term prognoses of MDS patients in the era of Aza treatment; high: p53-positive and poor cytogenetics, low: p53-negative and absence of poor cytogenetics, and intermediate: the others. OS was significantly different among the three groups according to this index (Low 92%, Intermediate 65% and High 27% at 12 months; P<0.0001). In conclusion, p53 expression was a significant prognostic factor in MDS patients treated with Aza. In combination with cytogenetic abnormalities, it is possible to make short-term prognoses. PMID:26651421

  7. Analysis of prognostic factors and comparison of prognostic scores in peripheral T cell lymphoma, not otherwise specified: a single-institution study of 105 Chinese patients.

    PubMed

    Xu, Pengpeng; Yu, Dong; Wang, Li; Shen, Yang; Shen, Zhixiang; Zhao, Weili

    2015-02-01

    Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous subtype of non-Hodgkin's lymphoma. This study aims to better define the prognostic factors and compare the predictive value of the prognostic scores in Chinese patients with PTCL-NOS. One hundred and five patients diagnosed as PTCL-NOS from our institution were retrospectively studied and grouped according to four previously described prognostic scores [International Prognostic Index (IPI), Prognostic Index for PTCL-NOS (PIT), modified PIT (m-PIT), and International PTCL Project (IPTCLP)]. In addition to clinical parameters, peripheral lymphopenia and thrombocytopenia, serum Epstein-Barr virus positivity, and tumor Ki-67 were significantly associated with poor disease outcome. Multivariate analysis revealed that age >60 years, poor performance status, elevated lactic dehydrogenase, and bone marrow involvement were independent adverse variables for survival. All prognostic scores were successful for survival estimation. Risk subgroups in IPI and PIT could be further discriminated by platelet count (IPTCLP factor) and Ki-67 (m-PIT factor), respectively. Together, patient- and tumor-specific characteristics may be incorporated in risk stratification of PTCL-NOS patients. The prognostic scores could be mutually active to improve their predictive value of disease outcome. PMID:25193354

  8. Periodic acid-Schiff-positive loops and networks as a prognostic factor in oral mucosal melanoma.

    PubMed

    Song, Hao; Jing, Guangping; Wang, Lizhen; Guo, Wei; Ren, Guoxin

    2016-04-01

    The prognostic factors of oral mucosal melanoma (OMM), a rare and aggressive neoplasm, remain to be determined. The aim of this study is to investigate the prognostic significance of vasculogenic mimicry in OMM. The clinical data of 62 patients with primary OMM treated in Shanghai Ninth People's Hospital from April 2007 to April 2012 were retrieved and analyzed retrospectively. Staining of periodic acid-Schiff (PAS) and CD31 immunohistochemistry were performed to evaluate the prognostic value of PAS-positive patterns, blood lakes, and microvascular density. PAS-positive loops and networks (P<0.001) as well as blood lakes (P=0.040) were found to be predictors of overall survival (OS). The presence of PAS-positive loops and networks was an independent prognostic factor of poor OS in multivariate analysis (P=0.002). Although the presence of PAS-positive loops and networks was associated with hematogenous metastasis (P=0.041) and lymphogenous metastasis (P=0.041), it was not an independent predictor of both types of metastasis in multivariate analysis. Microvascular density was not associated with OS (P=0.627) and metastasis of OMM patients. PAS-positive loops and networks have a significant prognostic value in OMM. Detection of PAS-positive patterns may lead to better staging and serve as a prognostic parameter of OMM. PMID:26636907

  9. Expression and prognostic relevance of PRAME in primary osteosarcoma

    SciTech Connect

    Tan, Pingxian; Zou, Changye; Yong, Bicheng; Han, Ju; Zhang, Longjuan; Su, Qiao; Yin, Junqiang; Wang, Jin; Huang, Gang; Peng, Tingsheng; Shen, Jingnian

    2012-03-23

    Graphical abstract: High PRAME expression was associated with osteosarcoma patients' poor prognosis and lung metastasis. Highlights: Black-Right-Pointing-Pointer We analyzed and verified the role of PRAME in primary osteosarcoma. Black-Right-Pointing-Pointer High PRAME expression in osteosarcoma correlated to poor prognosis and lung metastasis. Black-Right-Pointing-Pointer PRAME siRNA knockdown significantly suppressed the proliferation, colony formation, and G1 cell cycle arrest in U-2OS cells. -- Abstract: The preferentially expressed antigen of melanoma (PRAME), a cancer-testis antigen with unknown function, is expressed in many human malignancies and is considered an attractive potential target for tumor immunotherapy. However, studies of its expression and function in osteosarcoma have rarely been reported. In this study, we found that PRAME is expressed in five osteosarcoma cell lines and in more than 70% of osteosarcoma patient specimens. In addition, an immunohistochemical analysis showed that high PRAME expression was associated with poor prognosis and lung metastasis. Furthermore, PRAME siRNA knockdown significantly suppressed the proliferation, colony formation, and G1 cell cycle arrest in U-2OS cells. Our results suggest that PRAME plays an important role in cell proliferation and disease progression in osteosarcoma. However, the detail mechanisms of PRAME function in osteosarcoma require further investigation.

  10. Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications

    PubMed Central

    2013-01-01

    Background Cancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors. Methods The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival. Results Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively). Conclusions Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies. PMID:23731661

  11. Prognostic Significance of Survivin Expression in Osteosarcoma Patients: A Meta-Analysis

    PubMed Central

    Liu, Yugang; Teng, Zhaowei; Wang, Ying; Gao, Pengfei; Chen, Junli

    2015-01-01

    Background Osteosarcoma is the most common primary bone malignancy and has poor prognosis. Survivin has been identified as an independent prognostic factor for a majority of cancers. In the present study, we evaluated the effect of survivin expression on the clinical outcome of osteosarcoma patients. Material/Methods Online electronic databases were searched for related articles published between 2000 and 2015. Odds ratio (OR) and risk ratio (RR) with their 95% confidence intervals (CI) were employed to calculate the significance. Results Overall, a total of 20 relevant studies were selected, including 1030 patients. No significant heterogeneity was observed among included studies (P>0.01, I2<50%). Survivin was expressed in 68.6% of all cases. Our results show that survivin expression increased the 5-year overall survival (RR=0.48, 95% CI=0.32–0.71, P=0.0002) and rate of postoperative recurrence (RR=1.80, 95% CI=1.09–2.97, P=0.02). It was associated with the grade of osteosarcoma (Enneking clinical stage, IIb–III vs. I–IIa: OR=5.26, 95% CI=3.76–7.34, P<0.00001; Price’s grade, III vs. I+II: OR=2.04, 95% CI=1.16–3.61, P=0.01), metastasis, and soft tissue invasion of osteosarcoma (OR=6.25, 95% CI=3.74–10.45, P<0.00001; OR=6.15, 95% CI=3.74–10.11, P<0.00001). No relationship was found between survivin expression and sex, age, or tumor size in patients with osteosarcoma. Conclusions Our results suggest that survivin can function as a new diagnostic biomarker for osteosarcoma and be used as a reference index to determine pathology classification of osteosarcoma, providing new targets for gene therapy of osteosarcoma. PMID:26408642

  12. Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer

    SciTech Connect

    Leoutsakou, Theoni; Talieri, Maroulio; Scorilas, Andreas . E-mail: ascorilas@biol.uoa.gr

    2006-06-02

    The SR-related-CTD-associated-factors (SCAFs) have the ability to interact with the C-terminal domain of the RNA polymerase II, linking this way transcription to splicing. SRA1 (SR-A1) gene, encoding for a human high-molecular weight SCAF protein, is located on chromosome 19, between the IRF3 and the R-RAS oncogene and it has been demonstrated from members of our group that SRA1 is constitutively expressed in most of the human tissues, while it is overexpressed in a subset of ovarian tumors. In this study, we examine the expression of SRA1 gene in 111 ovarian malignant tissues and in the human ovarian carcinoma cell lines OVCAR-3, TOV21-G, and ES-2, using a semi-quantitative RT-PCR method. SRA1 gene was overexpressed in 61/111 (55%) of ovarian carcinomas. This higher expression was positively associated to the size of the tumor (p < 0.001), the grade and the stage of the disease (p = 0.003 and p = 0.006, respectively), and the debulking success (p < 0.001). Kaplan-Meier survival analysis revealed that lower SRA1 expression increases the probability of both the longer overall and the progression free survival of the patients. Multivariate Cox regression analysis revealed that SRA1 may be used as an independent prognostic biomarker in ovarian cancer. Our results suggest that SRA1 is associated with cancer progression and may possibly be characterized as a new marker of unfavorable prognosis for ovarian cancer.

  13. Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences.

    PubMed

    Blanco, Rancés; Domínguez, Elizabeth; Morales, Orlando; Blanco, Damián; Martínez, Darel; Rengifo, Charles E; Viada, Carmen; Cedeño, Mercedes; Rengifo, Enrique; Carr, Adriana

    2015-01-01

    The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction (p = 0.006) and proliferation index (p = 0.000). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate (p = 0.020) and multivariate (p = 0.010) analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended. PMID:26634172

  14. Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences

    PubMed Central

    Blanco, Rancés; Domínguez, Elizabeth; Morales, Orlando; Blanco, Damián; Martínez, Darel; Rengifo, Charles E.; Viada, Carmen; Cedeño, Mercedes; Rengifo, Enrique; Carr, Adriana

    2015-01-01

    The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction (p = 0.006) and proliferation index (p = 0.000). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate (p = 0.020) and multivariate (p = 0.010) analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended. PMID:26634172

  15. Is overexpression of TWIST, a transcriptional factor, a prognostic biomarker of head and neck carcinoma? Evidence from fifteen studies

    PubMed Central

    Zhuo, Xianlu; Luo, Huanli; Chang, Aoshuang; Li, Dairong; Zhao, Houyu; Zhou, Qi

    2015-01-01

    TWIST, a basic helix-loop-helix transcription factor, has been indicated to play a critical role in the progression of numerous malignant disorders. Published data on the significance of TWIST expression in head and neck carcinoma (HNC) risk have yielded conflicting results. Thus, we conducted a quantitative meta-analysis to obtain a precise estimate of this subject. After systematic searching and screening, a total of fifteen studies using immunohistochemistry for TWIST detection were included. The results showed that TWIST positive expression rate in HNC tissues was higher than that in normal tissues. TWIST expression might have a correlation with clinical features such as low differentiation, advanced clinical stage, presence of lymph node metastasis, distant metastasis and local recurrence (P < 0.05) , but not with age, gender, T stage and smoking as well as drinking (P > 0.05). In addition, over-expression of TWIST was a prognostic factor for HNC (HR = 1.92, 95% CI = 1.13–3.25). The data suggested that TWIST might play critical roles in cancer progression and act as a prognostic factor for HNC patients. PMID:26656856

  16. Supratentorial hemispheric ependymomas: an analysis of 109 adults for survival and prognostic factors.

    PubMed

    Hollon, Todd; Nguyen, Vincent; Smith, Brandon W; Lewis, Spencer; Junck, Larry; Orringer, Daniel A

    2016-08-01

    OBJECTIVE Survival rates and prognostic factors for supratentorial hemispheric ependymomas have not been determined. The authors therefore designed a retrospective study to determine progression-free survival (PFS), overall survival (OS), and prognostic factors for hemispheric ependymomas. METHODS The study population consisted of 8 patients from our institution and 101 patients from the literature with disaggregated survival information (n = 109). Patient age, sex, tumor side, tumor location, extent of resection (EOR), tumor grade, postoperative chemotherapy, radiation, time to recurrence, and survival were recorded. Kaplan-Meier survival analyses and Cox proportional hazard models were completed to determine survival rates and prognostic factors. RESULTS Anaplastic histology/WHO Grade III tumors were identified in 62% of cases and correlated with older age. Three-, 5-, and 10-year PFS rates were 57%, 51%, and 42%, respectively. Three-, 5-, and 10-year OS rates were 77%, 71%, and 58%, respectively. EOR and tumor grade were identified on both Kaplan-Meier log-rank testing and univariate Cox proportional hazard models as prognostic for PFS and OS. Both EOR and tumor grade remained prognostic on multivariate analysis. Subtotal resection (STR) predicted a worse PFS (hazard ratio [HR] 4.764, p = 0.001) and OS (HR 4.216, p = 0.008). Subgroup survival analysis of patients with STR demonstrated a 5- and 10-year OS of 28% and 0%, respectively. WHO Grade III tumors also had worse PFS (HR 10.2, p = 0.004) and OS (HR 9.1, p = 0.035). Patients with WHO Grade III tumors demonstrated 5- and 10-year OS of 61% and 46%, respectively. Postoperative radiation was not prognostic for PFS or OS. CONCLUSIONS A high incidence of anaplastic histology was found in hemispheric ependymomas and was associated with older age. EOR and tumor grade were prognostic factors for PFS and OS on multivariate analysis. STR or WHO Grade III pathology, or both, predicted worse overall prognosis in patients

  17. Prognostic values of four Notch receptor mRNA expression in gastric cancer

    PubMed Central

    Wu, Xiaoyu; Liu, Wentao; Tang, Ding; Xiao, Haijuan; Wu, Zhenfeng; Chen, Che; Yao, Xuequan; Liu, Fukun; Li, Gang

    2016-01-01

    Notch ligands and receptors are frequently deregulated in several human malignancies including gastric cancer. The activation of Notch signaling has been reported to contribute to gastric carcinogenesis and progression. However, the prognostic roles of individual Notch receptors in gastric cancer patients remain elusive. In the current study, we accessed the prognostic roles of four Notch receptors, Notch 1–4, in gastric cancer patients through “The Kaplan-Meier plotter” (KM plotter) database, in which updated gene expression data and survival information include a total of 876 gastric cancer patients. All four Notch receptors’ high mRNA expression was found to be correlated to worsen overall survival (OS) for all gastric cancer patients followed for 20 years. We further accessed the prognostic roles of individual Notch receptors in different clinicopathological features using Lauren classification, pathological grades, clinical grades, HER2 status and different choices of treatments of gastric cancer patients. These results indicate that there are critical prognostic values of the four Notch receptors in gastric cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of gastric cancer and to develop tools to more accurately predict their prognosis. PMID:27363496

  18. MARCKS Regulates Growth, Radiation Sensitivity and is a Novel Prognostic Factor for Glioma

    PubMed Central

    Jarboe, John S.; Anderson, Joshua C.; Duarte, Christine W.; Mehta, Tapan; Nowsheen, Somaira; Hicks, Patricia H.; Whitley, Alexander C.; Rohrbach, Timothy D.; McCubrey, Raymond O.; Chiu, Sherard; Burleson, Tamara M.; Bonner, James A.; Gillespie, G. Yancey; Yang, Eddy S.; Willey, Christopher D.

    2013-01-01

    Purpose This study assessed whether Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) can regulate glioblastoma (GBM) growth, radiation sensitivity and clinical outcome. Experimental Design MARCKS protein levels were analyzed in five GBM explant cell lines and eight patient-derived xenograft tumors by immunoblot, and these levels were correlated to proliferation rates and intracranial growth rates, respectively. Manipulation of MARCKS protein levels was assessed by lentiviral-mediated shRNA knockdown in the U251 cell line and MARCKS over-expression in the U87 cell line. The effect of manipulation of MARCKS on proliferation, radiation sensitivity and senescence was assessed. MARCKS gene expression was correlated with survival outcomes in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) Database and The Cancer Genome Atlas (TCGA). Results MARCKS protein expression was inversely correlated with GBM proliferation and intracranial xenograft growth rates. Genetic silencing of MARCKS promoted GBM proliferation and radiation resistance, while MARCKS overexpression greatly reduced GBM growth potential and induced senescence. We found MARCKS gene expression to be directly correlated with survival in both the REMBRANDT and TCGA databases. Specifically, patients with high MARCKS expressing tumors of the Proneural molecular subtype had significantly increased survival rates. This effect was most pronounced in tumors with unmethylated O6-methylguanine DNA methyltransferase (MGMT) promoters, a traditionally poor prognostic factor. Conclusions MARCKS levels impact GBM growth and radiation sensitivity. High MARCKS expressing GBM tumors are associated with improved survival, particularly with unmethylated MGMT promoters. These findings suggest the use of MARCKS as a novel target and biomarker for prognosis in the Proneural subtype of GBM. PMID:22619307

  19. Prognostic significance of Dicer expression in hepatocellular carcinoma

    PubMed Central

    ZHANG, LI; WANG, CUIJU; LIU, SHUFENG; ZHAO, YUFEI; LIU, CHAO; GUO, ZHANJUN

    2016-01-01

    Dicer is a RNaseIII endonuclease of the microRNA processing pathway, which is implicated in carcinogenesis of various types of human cancer. The present study assessed the expression level of Dicer in hepatocellular carcinoma (HCC) tissue to evaluate its association with HCC tumorigenesis. A low expression of Dicer was significantly associated with a shorter postoperative survival time of patients with HCC, which was assessed using the log-rank test with Kaplan-Meier survival analysis. Multivariate analysis identified that Dicer expression was an independent predictor for HCC outcome (relative risk, 0.660; 95% confidence interval, 0.506–0.861; P=0.002). A functional assay demonstrated that Dicer overexpression inhibited the proliferation and promoted the apoptosis of HCC cells. In addition, a Transwell assay revealed that Dicer markedly inhibited the migration and invasion of HCC cells. The present findings indicate that Dicer expression modified the outcomes of HCC patients by inhibiting proliferation, promoting apoptosis and inhibiting metastasis of HCC cells. PMID:27313724

  20. Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas.

    PubMed

    Lundberg, Marie; Renkonen, Suvi; Haglund, Caj; Mattila, Petri S; Leivo, Ilmo; Hagström, Jaana; Mäkitie, Antti A

    2016-05-01

    Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC. Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations. Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other. Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997-2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry. Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T- and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found. PMID:27052966

  1. Prognostic parameters in uveal melanoma and their association with BAP1 expression

    PubMed Central

    van Essen, T Huibertus; van Pelt, Sake I; Versluis, Mieke; Bronkhorst, Inge HG; van Duinen, Sjoerd G; Marinkovic, Marina; Kroes, Wilma GM; Ruivenkamp, Claudia AL; Shukla, Shruti; de Klein, Annelies; Kiliç, Emine; Harbour, J William; Luyten, Gregorius PM; van der Velden, Pieter A; Verdijk, Rob M; Jager, Martine J

    2016-01-01

    Aim To determine whether BAP1 gene and protein expression associates with different prognostic parameters in uveal melanoma and whether BAP1 expression correctly identifies patients as being at risk for metastases, following enucleation of the primary tumour. Methods Thirty cases of uveal melanoma obtained by enucleation between 1999 and 2004 were analysed for a variety of prognostic markers, including histological characteristics, chromosome aberrations obtained by fluorescence in situ hybridisation (FISH) and single nucleotide polymorphism (SNP) analysis and gene expression profiling. These parameters were compared with BAP1 gene expression and BAP1 immunostaining. Results The presence of monosomy of chromosome 3 as identified by the different chromosome 3 tests showed significantly increased HRs (FISH on isolated nuclei cut-off 30%: HR 11.6, p=0.002; SNP analysis: HR 20.3, p=0.004) for death due to metastasis. The gene expression profile class 2, based on the 15-gene expression profile, similarly provided a significantly increased HR for a poor outcome (HR 8.5, p=0.005). Lower BAP1 gene expression and negative BAP1 immunostaining (50% of 28 tumours were immunonegative) were both associated with these markers for prognostication: FISH cut-off 30% monosomy 3 (BAP1 gene expression: p=0.037; BAP1 immunostaining: p=0.001), SNP-monosomy 3 (BAP1 gene expression: p=0.008; BAP1 immunostaining: p=0.002) and class 2 profile (BAP1 gene expression: p<0.001; BAP1 immunostaining: p=0.001) and were themselves associated with an increased risk of death due to metastasis (BAP1 gene expression dichotomised: HR 8.7, p=0.006; BAP1 immunostaining: HR 4.0, p=0.010). Conclusions Loss of BAP1 expression associated well with all of the methods currently used for prognostication and was itself predictive of death due to metastasis in uveal melanoma after enucleation, thereby emphasising the importance of further research on the role of BAP1 in uveal melanoma. PMID:25147369

  2. A systematic review of prognostic factors for distal upper limb pain

    PubMed Central

    Whibley, Daniel; Martin, Kathryn R; Lovell, Karina; Jones, Gareth T

    2015-01-01

    Background: Musculoskeletal pain in the distal upper limb is relatively common, can be a cause of disability, presents a high cost to society and is clinically important. Previous reviews of prognostic factors have focused on pain in the proximal upper limb, whole upper extremity or isolated regions of the distal upper limb. Aim: To identify factors that predict outcome of distal upper limb pain. Study design: Systematic review Method: Eight bibliographic databases were searched from inception to March 2014. Eligible articles included adults with pain anywhere in the distal upper limb at baseline from randomised controlled trials with a waiting list, expectant policy or usual care group, or observational studies where no treatment or usual care was provided. Data describing the association between a putative prognostic factor and pain or functional outcome at follow-up were required. Quality was assessed using the Quality in Prognostic Studies tool. Results: Seven articles reporting on six studies were identified. Heterogeneity of study populations and outcome measures prevented a meta-analysis so a narrative synthesis of results was undertaken. Three factors (being female, a longer duration of the complaint at initial presentation and having musculoskeletal pain in multiple locations) were significantly associated with poor pain outcome in more than one study. Being female was the only factor significantly associated with poor functional outcome in more than one study. Conclusions: A range of sociodemographic, pain-related, occupational and psychosocial prognostic factors for distal upper limb pain outcomes were investigated in studies included in the review. However, due to the lack of commonality of factors investigated and lack of consistency of results across studies, there is limited evidence for predictors of distal upper limb pain outcomes. Further research is required to identify prognostic factors of distal upper limb pain, particularly modifiable factors

  3. Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma

    PubMed Central

    Jang, Ye-Rang; Kim, Hyeyoung; Lee, Jeong-Moo; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    Backgrounds/Aims In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2). PMID:26693236

  4. Long Noncoding RNA Expression Signatures of Metastatic Nasopharyngeal Carcinoma and Their Prognostic Value

    PubMed Central

    Zhang, Wei; Wang, Lin; Zheng, Fang; Zou, Ruhai; Xie, Changqing; Guo, Qiannan; Hu, Qian; Chen, Jianing; Yang, Xing; Yao, Herui; Song, Erwei; Xiang, Yanqun

    2015-01-01

    Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (≥2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (P = 0.01). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment. PMID:26448942

  5. KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas.

    PubMed

    Becker, Aline Paixão; Scapulatempo-Neto, Cristovam; Carloni, Adriana C; Paulino, Alessandra; Sheren, Jamie; Aisner, Dara L; Musselwhite, Evelyn; Clara, Carlos; Machado, Hélio R; Oliveira, Ricardo S; Neder, Luciano; Varella-Garcia, Marileila; Reis, Rui M

    2015-07-01

    Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable. PMID:26083571

  6. Prognostic Utility of Apoptosis Index, Ki-67 and Survivin Expression in Dogs with Nasal Carcinoma Treated with Orthovoltage Radiation Therapy

    PubMed Central

    FU, Dah-Renn; KATO, Daiki; WATABE, Ai; ENDO, Yoshifumi; KADOSAWA, Tsuyoshi

    2014-01-01

    ABSTRACT Apoptosis, Ki-67 and survivin expression have been reported as prognostic values in human cancer treated with radiation therapy. The aim of this study was to evaluate the correlation between the outcome of canine nasal carcinomas treated with radiation therapy and these cancer markers. The apoptotic index (AI) was evaluated with TUNEL assays, and an immunohistochemical evaluation was performed on Ki-67 and survivin in 33 biopsy samples taken before treatment. Median survival times were estimated using Kaplan-Meier curves and the log-rank method. The AI ranged from 0 to 0.7%, and the percentage of Ki-67-positive cells defined as the proliferative index (PI) ranged from 0.8 to 77% in all samples. Neither the AI nor the PI had a significant relationship with survival time (P=0.056 and 0.211). Survivin expression was detected in 84.9% of samples of canine nasal carcinoma. Dogs with high survivin expression were associated with poorer response to treatment and had shorter survival times (P=0.017 and 0.031). Advanced-stage tumors were also significantly associated with a high level of survivin (P=0.026). Overexpression of survivin was shown to be an unfavorable prognostic factor in dogs with nasal carcinomas treated with radiation therapy. PMID:25452259

  7. Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

    PubMed Central

    ZHAO, DAHANG; LIU, XIANGJIE; ZHANG, YUNGE; DING, ZHAOMING; DONG, FENG; XU, HONGWEI; WANG, BAOXIN; WANG, WENBO

    2016-01-01

    Osteosarcoma is the most prevalent type of primary malignant bone tumor. Inhibitor of growth 4 (ING4) has been demonstrated to function as a tumor suppressor through multiple pathways, and is its expression is understood to be suppressed or reduced in various malignancies. The present study aimed to investigate the expression of ING4 and to determine its prognostic value in osteosarcoma tissue. Formalin-fixed, paraffin-embedded tissue microarrays were analyzed, and contained 41 osteosarcoma specimens and 11 normal bone tissue specimens with duplicate cores. ING4 expression was evaluated by immunohistochemical staining. The association between ING4 expression in the osteosarcoma and normal bone tissues was analyzed, in addition to the association between ING4 expression and Enneking classification of the osteosarcoma tissues. A significant statistical difference was observed in the ING4 immunohistochemical staining score between the osteosarcoma and normal bone tissues (P<0.001). Furthermore, a significant negative correlation was detected between the ING4 immunohistochemical staining scores and the Enneking classification results of the 41 osteosarcoma tissues (P=0.002). Low expression of ING4 was observed in the osteosarcoma specimens, and this reduced expression of ING4 was negatively correlated with Enneking classification. Thus, the results of the present study indicate that ING4 may serve as a promising prognostic marker in osteosarcoma. PMID:27073567

  8. [Analysis of prognostic correlated factors of 49 patients with mucosa-associated lymphoid tissue lymphoma].

    PubMed

    Jing, Hong-Mei; Ke, Xiao-Yan; Dong, Fei

    2007-12-01

    The aim of this study was to investigate the clinical feature of mucosa-associated lymphoid tissue lymphoma and clarify the relationship between the pathological, clinical features, the expression of API2-MALT1 and the prognosis. A number of factors including pathological characters, grade, stage, prognosis and treatment of 49 cases of MALT lymphoma were analyzed, and the API2-MALT1 rearrangement was detected by RT-PCR. The results showed that 49 patients were diagnosed as MALT lymphoma, in which median age was 52.4 years. The percentage of patients older than 50 years was 67.3%. The majority of tumors were found in stomach (22 cases), intestine (13 cases), thyroid (6 cases) and so on. Among 49 patients, stage I, II was 77. 6%, stage III, IV was 22.4%. API2-MALT1 rearrangement were found 38.1% in low grade, and 12.5% in transform type. Among 18 patients with gastric MALT lymphoma, 9 cases (50.0%) were helicobacter pylori (HP) positive and received antibiotic treatment. The 3 years overall survival was 93.8%. It is concluded that MALT lymphoma is often seen in older patients, most of them were in low grade with slow progression. The site, grade, stage and molecular genetic changes are important prognostic factors, which can contribute to choosing suitable treatment for patients with MALT lymphoma. The antibiotic treatment is effective for patients with positive HP. PMID:18088487

  9. Interleukin 6 Receptor Is an Independent Prognostic Factor and a Potential Therapeutic Target of Ovarian Cancer

    PubMed Central

    Isobe, Aki; Sawada, Kenjiro; Kinose, Yasuto; Ohyagi-Hara, Chifumi; Nakatsuka, Erika; Makino, Hiroshi; Ogura, Tomonori; Mizuno, Tomoko; Suzuki, Noriko; Morii, Eiichi; Nakamura, Koji; Sawada, Ikuko; Toda, Aska; Hashimoto, Kae; Mabuchi, Seiji; Ohta, Tsuyoshi; Morishige, Ken-ichirou; Kurachi, Hirohisa; Kimura, Tadashi

    2015-01-01

    Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment. PMID:25658637

  10. The Role of Steroid Sulfatase as a Prognostic Factor in Patients with Endometrial Cancer

    PubMed Central

    Lee, Won Moo; Jang, Ki-Seok; Koh, A Ra

    2016-01-01

    Purpose The aim of the study was to determine steroid sulfatase (STS) expression in endometrial cancer patients and its correlation with disease prognosis. Materials and Methods We conducted a retrospective study in 59 patients who underwent surgery with histologically confirmed endometrial cancer from January 2000 to December 2011 at Hanyang University Hospital. Immuno-histochemical staining of STS was performed using rabbit polyclonal anti-STS antibody. Results Sixteen of the 59 patients (27.1%) were positive for STS expression. Disease free survival (DFS) was 129.83±8.67 [95% confidence interval (CI): 112.84–146.82] months in the STS positive group (group A) and 111.06±7.17 (95% CI: 97.01–125.10) months in the STS negative group (group B) (p=0.92). Overall survival (OS) was 129.01±9.38 (95% CI: 110.63–147.38) months and 111.16±7.10 (95% CI: 97.24–125.07) months for the groups A and B, respectively (p=0.45). Univariate analysis revealed that FIGO stage and adjuvant therapy are significantly associated with DFS and OS. However, in multivariate analysis, FIGO stage and adjuvant therapy did not show any statistical significance with DFS and OS. STS was also not significantly associated with DFS and OS in univariate and multivariate analysis. Conclusion STS expression was not significantly associated with DFS and OS, despite positive STS expression in 27% of endometrial cancer patients. Therefore, the role of STS as a prognostic factor in patients with endometrial cancer remains unclear and requires further research. PMID:26996578

  11. Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors

    PubMed Central

    Cho, Gene Young; Moy, Linda; Kim, Sungheon G.; Baete, Steven H.; Moccaldi, Melanie; Babb, James S.; Sodickson, Daniel K.; Sigmund, Eric E.

    2016-01-01

    Purpose To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. Materials and methods This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44±11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann–Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman’s rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. Results The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Conclusion Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. PMID:26615557

  12. Coexistence of HER2, Ki67, and p53 in Osteosarcoma: A Strong Prognostic Factor

    PubMed Central

    Mardanpour, Keykhosro; Rahbar, Mahtab; Mardanpour, Sourena

    2016-01-01

    Background: Many laboratories are currently evaluating the usefulness of the determination of human epidermal growth factor receptor 2 (HER2), p53, and Ki67 proliferation indices using immunohistochemical techniques in cancer. Although the available studies suggest that these factors might indeed be helpful in making treatment decisions in osteosarcoma patients, their clinical usefulness is still controversial. Aims: We proposed to introduce the value of the coexistence of HER2 overexpression, p53 protein accumulation, and Ki67 in osteosarcoma, which could be a prognostic factor in osteosarcoma. Material and Methods: Expression of HER2, p53, and Ki67 was examined by immunohistochemistry in samples of resected bone tumor tissue from 56 patients with osteosarcoma, obtained between 2009 and 2014 (median follow-up period of 48 months), and their significance for prognosis was analyzed. Results: Of the 56 osteogenic sarcoma tissue samples, 80, 89, and 96.5% were positive for HER2 overexpression, p53 protein accumulation, and Ki67 expression, respectively. Overexpression of HER2 and accumulation of p53 protein significantly correlated with reduced disease-free (P < 0.01) and overall survival (P < 0.003). HER2 and Ki67 co-overexpression significantly correlated with decreased disease-free (P < 0.03) and overall survival (P < 0.02). HER2, accumulation of p53 protein, and Ki67 co-overexpression significantly correlated with reduced disease-free (P < 0.01) and overall survival (P < 0.005) as did patients with larger tumor size, high grade of tumor, positive lymph node, and metastasis status within the specified period of follow up. Conclusions: We found evidence that coexistence of HER2 and Ki67 overexpression and p53 protein accumulation predict the development of lymph node involvement and metastases in patients with high-grade osteosarcoma and were significantly associated with reduced survival. PMID:27298815

  13. Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

    PubMed Central

    Stoecklein, Nikolas H; Siegmund, Annika; Scheunemann, Peter; Luebke, Andreas M; Erbersdobler, Andreas; Verde, Pablo E; Eisenberger, Claus F; Peiper, Matthias; Rehders, Alexander; Esch, Jan Schulte am; Knoefel, Wolfram Trudo; Hosch, Stefan B

    2006-01-01

    Background To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. Methods The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. Results Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. Conclusion Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention. PMID:16796747

  14. Prognostic significance of TAZ expression in various cancers: a meta-analysis

    PubMed Central

    Feng, Juntao; Ren, Pengwei; Gou, Jinhai; Li, Zhengyu

    2016-01-01

    Background The overexpression of transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo pathway effector, was detected in a variety of cancers. However, controversies remain in published studies on the prognostic value of TAZ expression in cancer. We performed a meta-analysis to demonstrate the prognostic significance of TAZ in overall survival (OS) and its association with clinicopathologic characteristics. Methods A systematic literature search was performed by using PubMed, EMBASE, and Web of Science databases for eligible studies investigating the association between TAZ and survival. After extracting data, we used hazard ratio (HR), odds ratio (OR) and 95% confidence intervals (95% CIs) for association evaluation, I2 for heterogeneity across studies, and Egger’s test and Begg’s funnel plot for publication bias assessment. Results A total of 15 studies including 2,881 patients were analyzed. Pooled results showed that a high TAZ was significantly associated with poor OS (HR =1.82, 95% CI =1.58–2.11; I2=33%; P=0.11). Subgroup analysis indicated significant correlation between TAZ overexpression and OS in patients stratified by ethnicity, sample size, sample source, and staining location. Furthermore, TAZ overexpression was associated with worse OS in hepatocellular carcinoma (HR =2.26, 95% CI =1.43–3.57; P=0.49) and gastrointestinal cancers (HR =2.00, 95% CI =1.54–2.58; P=0.97), but not in non-small-cell lung cancer (HR =1.71, 95% CI =0.93–3.14; P=0.08). TAZ overexpression was also found to be significantly associated with some clinicopathologic characteristics, including TNM stage (OR =2.56, 95% CI =1.60–4.11; P=0.52), tumor differentiation (OR =3.08, 95% CI =1.25–7.63; P=0.01), and lymph node metastasis (OR =2.53, 95% CI =1.81–3.53; P=0.58). Conclusion TAZ overexpression is not only a predictive factor of poor prognosis but also associated with advanced TNM stage, poor tumor differentiation, and lymph node metastasis. PMID:27601916

  15. A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone.

    PubMed

    O'Shea, Matthew K; Clay, Katherine A; Craig, Darren G; Moore, Alastair J; Lewis, Stephen; Espina, Melanie; Praught, Jeff; Horne, Simon; Kao, Raymond; Johnston, Andrew M

    2016-04-01

    We describe the management of a Sierra Leonean health care worker with severe Ebola virus disease complicated by diarrhea, significant electrolyte disturbances, and falciparum malaria coinfection. With additional resources and staffing, high quality care can be provided to patients with Ebola infection and adverse prognostic factors in west Africa. PMID:26903609

  16. Change in Quality of Life after Rehabilitation: Prognostic Factors for Visually Impaired Adults

    ERIC Educational Resources Information Center

    Langelaan, Maaike; de Boer, Michiel R.; van Nispen, Ruth M. A.; Wouters, Bill; Moll, Annette C.; van Rens, Ger H. M. B.

    2009-01-01

    The overall aim of rehabilitation for visually impaired adults is to improve the quality of life and (societal) participation. The objectives of this study were to obtain the short-term and long-term outcome of a comprehensive rehabilitation programme on quality of life for visually impaired adults, and prognostic baseline factors responsible for…

  17. Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma.

    PubMed

    Wu, Wenting; Lamborn, Kathleen R; Buckner, Jan C; Novotny, Paul J; Chang, Susan M; O'Fallon, Judith R; Jaeckle, Kurt A; Prados, Michael D

    2010-02-01

    The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980-2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998-2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint. PMID:20150383

  18. Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma

    PubMed Central

    Wu, Wenting; Lamborn, Kathleen R.; Buckner, Jan C.; Novotny, Paul J.; Chang, Susan M.; O'Fallon, Judith R.; Jaeckle, Kurt A.; Prados, Michael D.

    2010-01-01

    The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980–2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998–2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint. PMID:20150383

  19. Clinical features, outcome and prognostic factors of 87 patients with angioimmunoblastic T cell lymphoma in Taiwan.

    PubMed

    Kao, Hsiao-Wen; Lin, Tung-Liang; Shih, Lee-Yung; Dunn, Po; Kuo, Ming-Chung; Hung, Yu-Shin; Wu, Jin-Hou; Tang, Tzung-Chih; Chang, Hung; Kuo, Tseng-Tong; Ou, Che-Wei; Wang, Po-Nan

    2016-08-01

    We retrospectively analyzed 87 patients with angioimmunoblastic T cell lymphoma (AITL) in Taiwan. The median age was 68 (range 18-89) years. Of these patients, 74 % was at an advanced stage. The most common extra-nodal site involved was bone marrow (36 %). Of these patients, 77 % were International Prognostic Index (IPI) >1 and 79 % had a prognostic index for peripheral T-cell lymphoma (PIT) >1. Of 75 patients who received systemic chemotherapy, the complete remission rate was 60 %, the relapse rate was 47 %, and the 2-year progression-free survival rate was 37.4 %. The 2-year overall survival (OS) rate for all patients was 51.9 %. By multivariate analysis, bone marrow involvement (P < 0.001) and ECOG >1 (P = 0.007) were independent adverse factors for OS. A simplified prognostic index efficiently stratified patients into the following three groups: 2-year OS rates 79.8 % (0 factor), 28.3 % (1 factor), and 10.2 % (2 factors) by using bone marrow involvement and ECOG >1 (P < 0.001). In conclusion, AITL patients were older and had poorer prognosis in Taiwan. Bone marrow involvement, EOCG >1, IPI >1 and PIT >1 had adverse impact on OS. The usefulness of this simplified prognostic index needs further validation. PMID:27095042

  20. Assessing the influence of treating therapist and patient prognostic factors on recovery from axial pain

    PubMed Central

    Simon, Corey B; Stryker, Sandra E; George, Steven Z

    2013-01-01

    Background: Limited research exists regarding the influence of a treating physical therapist on patient recovery (deemed therapist effects). Recent randomized clinical trials data provide an indication of small therapist effects for manual therapy; however, the extent to which therapist effects exist in the average outpatient facility is not clear. Moreover, patient-related prognostic factors, like fear-avoidance or pain duration, are important to consider since these may also influence the extent of therapist effects. Objective: To assess therapist effects and the influence of patient prognostic factors on recovery from axial pain in an outpatient orthopedic physical therapy facility. Methods: Clinical data were collected from consecutive patients with musculoskeletal neck and low back pain. Patient outcomes included pain intensity (visual analog scale) and functional measure (CareConnections functional outcomes index) scores. Therapist effects estimates and the influence of intake fear-avoidance (fear-avoidance beliefs questionnaire) and pain duration (days) were examined using multilevel linear or regression modeling. Results: A total of 258 patients (160 females; mean age 46.4±14.9 years) completed physical therapy and the required outcome measures. Five physical therapists (1–13 years of experience, mean 5.8 years) provided treatment. Therapists effects did not exist for discharge pain intensity or function after accounting for intake scores (P > 0.05). Further, therapist experience did not influence patient outcomes. Patient prognostic factors of fear-avoidance and pain duration did not influence therapists effects on the same patient outcome measures (P > 0.05). Discussion: Preliminary findings suggest that there are no major differences in patient outcome based on either the individual therapist (therapist effect) or therapist experience in this type of PT setting. Established prognostic factors had no influence on therapist effects for this cohort

  1. Prognostic Significance of MiR-34a Expression in Patients with Gastric Cancer after Radical Gastrectomy

    PubMed Central

    Hui, Wen-Tao; Ma, Xiao-Bin; Zan, Ying; Wang, Xi-Jing; Dong, Lei

    2015-01-01

    Background: MiR-34a dysregulation has been implicated in tumorigenesis and progression of gastric cancer, but its role in prognosis of patients with gastric cancer remains unknown. The aim of this study was to investigate the expression and prognostic significance of miR-34a in gastric cancer patients after radical gastrectomy. Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-34a in human gastric cancer cell lines and tissues in 76 patients with gastric adenocarcinoma from China. Results are assessed for association with clinical features and overall survival (OS) using Kaplan–Meier analysis. Prognostic values of miR-34a expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating miR-34a expression was determined using receiver operating characteristic analysis. Results: The results show that the expression level of miR-34a was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-34a was associated with Lauren classification (P = 0.034). Decreased miR-34a expression in gastric cancer tissues was positively correlated with poor OS of gastric cancer patients (P = 0.013). Further multivariate Cox regression analysis suggested that miR-34a expression was an independent prognostic indicator for gastric cancer (P = 0.027). Applying the prognostic value of miR-34a expression to tumor node metastasis (TNM) stage system showed a better prognostic value in patients with gastric cancer than miR-34a expression (P = 0.0435) or TNM stage (P = 0.0249) alone. Conclusion: The results reinforce the critical role for the down-regulated miR-34a expression in gastric cancer and suggest that miR-34a could be a prognostic indicator for this disease. PMID:26415802

  2. Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype

    PubMed Central

    Grelier, G; Voirin, N; Ay, A-S; Cox, D G; Chabaud, S; Treilleux, I; Léon-Goddard, S; Rimokh, R; Mikaelian, I; Venoux, C; Puisieux, A; Lasset, C; Moyret-Lalle, C

    2009-01-01

    Background: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. Methods: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription–PCR. Results: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours. Conclusion: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer. PMID:19672267

  3. Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer

    PubMed Central

    Lee, Ji-Hye; Son, Myoung-Won; Kim, Kyung-Ju; Oh, Mee-Hye; Cho, Hyundeuk; Lee, Hyun Ju; Jang, Si-Hyong

    2016-01-01

    Purpose Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions We suggested that TLE1 expression is a good prognostic indicator in GCs. PMID:27104023

  4. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors

    PubMed Central

    Kanas, Gena P; Taylor, Aliki; Primrose, John N; Langeberg, Wendy J; Kelsh, Michael A; Mowat, Fionna S; Alexander, Dominik D; Choti, Michael A; Poston, Graeme

    2012-01-01

    Background Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. Methods Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. Results Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7–7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5–1.7); carcinoembryonic antigen level, 1.9 (1.1–3.2); extrahepatic disease, 1.9 (1.5–2.4); poor tumor grade, 1.9 (1.3–2.7); positive margin, 2.0 (1.7–2.5); >1 liver metastases, 1.6 (1.4–1.8); and >3 cm tumor diameter, 1.5 (1.3–1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. Conclusion The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival. PMID:23152705

  5. ZO-1 expression shows prognostic value in chronic B cell leukemia.

    PubMed

    Nesmiyanov, Pavel P; Tolkachev, Boris E; Strygin, Andrey V

    2016-01-01

    Connexin-mediated gap junctions are vital for tumor cell function. Intracellular pathways of connexin signaling use Zonula Occludens protein-1 (ZO-1) as an intermediate. This report describes the ZO-1 and connexin 43 (Cx43) expression pattern in lymphocytes from chronic B-cell leukemia (B-CLL) patients. The ZO-1 and Cx43 expression in the B cells of 113 B-CLL patients was identified. Western blot and flow cytometry were used to determine protein expression. Results indicated that ZO-1 and Cx43 expression was reduced and correlated negatively with CD38 and Zap-70 expression. Inhibition of intercellular communication with anti-Cx43 antibodies, 1-octanol, or carbenoxolone resulted in induced cell apoptosis. These data suggest that ZO-1, along with CD38 and Zap-70, plays a role in cell cycle regulation in B-CLL and may be used as a prognostic marker in B-CLL monitoring. PMID:26306999

  6. Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinoma

    PubMed Central

    2014-01-01

    Introduction The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract. Materials and methods Immunohistochemical PIGR expression was examined in a consecutive cohort of patients with surgically resected, radio-chemonaive adenocarcinoma of the esophagus, GE-junction and stomach (n = 173), including paired samples of benign-appearing squamous epithelium (n = 51), gastric mucosa (n = 114), Barrett’s esophagus (BE) or intestinal metaplasia (IM) (n = 57) and lymph node metastases (n = 75). Non-parametric tests were applied to explore associations between PIGR expression in primary tumours and clinicopathological characteristics. Classification and regression tree analysis was applied for selection of prognostic cut-off. The impact of PIGR expression on overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier analysis and hazard ratios (HR) calculated by adjusted and unadjusted Cox proportional hazards modelling. Results PIGR expression was significantly higher in intestinal metaplasia (BE or gastric IM) compared to normal tissues and cancer (p < 0.001). Reduced PIGR expression in primary tumours was significantly associated with more advanced tumour stage (p = 0.002) and inversely associated with involved margins (p = 0.034). PIGR expression did not differ between primary tumours and lymph node metastases. There was no significant difference in PIGR expression between tumours with and without a background of intestinal metaplasia. High PIGR expression was an independent predictor of a

  7. Prognostic value of cancer stem cell marker CD133 expression in esophageal carcinoma: A meta-analysis

    PubMed Central

    SUI, YUN-PENG; JIAN, XUE-PING; MA, LI; XU, GUI-ZHEN; LIAO, HUAI-WEI; LIU, YAN-PING; WEN, HUI-CAI

    2016-01-01

    CD133 has been identified as a putative neoplastic stem cell marker in esophageal carcinoma. However, the prognostic value of CD133 overexpression in patients with esophageal carcinoma remains controversial. A meta-analysis of previous studies was performed, in order to assess the association of CD133 overexpression with the clinicopathological characteristics of esophageal carcinoma patients. A total of 7 studies, including 538 patients, were subjected to the final analysis. Our results indicated that a positive CD133 expression was significantly associated with lymph node metastasis [odds ratio (OR)=3.09, 95% confidence interval (CI): 1.93–4.95; P<0.00001], clinical stage (OR=4.26, 95% CI: 1.55–11.73; P=0.005) and histopathological grade (OR=2.40, 95% CI: 1.16–4.94; P=0.02). There was no statistically significant association of CD133 with depth of invasion (OR=1.89, 95% CI: 0.42–8.43; P=0.41). Based on the results of this study, we concluded that CD133 is an efficient prognostic factor in esophageal carcinoma. Higher CD133 expression is significantly associated with lymph node metastasis, clinical stage and histopathological grade. PMID:26870362

  8. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients.

    PubMed

    Guillevin, L; Lhote, F; Gayraud, M; Cohen, P; Jarrousse, B; Lortholary, O; Thibult, N; Casassus, P

    1996-01-01

    We undertook this study to determine the clinical, biologic, immunologic, and therapeutic factors associated with the prognoses of polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). Three hundred forty-two patients (260 with PAN, 82 with CSS) followed from 1980 to 1993 were included in a prospective study on prognostic factors. Two hundred eighty-eight of these patients were included in the prospective studies on PAN and CSS. Items to be considered for analysis were collected at the time of diagnosis, during the acute phase of the disease. A survival curve was plotted for each clinical and biologic symptom observed in PAN or CSS. Each treatment arm of the prospective therapeutic trials was also tested: 1) prednisone (CS) + oral cyclophosphamide (CYC) + plasma exchanges (PE) versus CS E, 2) CS + PE versus CS, 3) CS + oral CY versus CS + pulse CY, 4) CS + pulse CY + PE versus CS + pulse CY in severe PAN and CSS, and 5) PE + antiviral agents after short-term CS in hepatitis B virus-related PAN. Of the parameters thus evaluated, the following had significant prognostic value and were responsible for higher mortality: proteinuria > 1 g/d (p < 0.0001; relative risk [RR] 3.6), renal insufficiency with serum creatinine > 1.58 mg/DL (p < 0.02; RR 1.86), GI tract involvement (p < 0.008. RR 2.83 for surgery). Cardiomyopathy and CNS involvement were associated with a RR of mortality of 2.18 and 1.76, respectively; these were not statistically significant. Similar survival rates were obtained with the prospectively tested therapies. The five-factors score (FFS) we established considered the prognostic factors creatinemia, proteinuria, cardiomyopathy, GI tract involvement, and CNS signs. Multivariate analysis showed that proteinuria (due to vascular or glomerular disease) and GI tract involvement were independent prognostic factors. When FFS = 0 (none of the 5 prognostic factors present), mortality at 5 years was 11.9%; when FFS = 1 (1 of the 5 factors present

  9. Clinical, pathological and molecular prognostic factors in prostate cancer decision-making process.

    PubMed

    Pugliese, Dario; Palermo, Giuseppe; Totaro, Angelo; Bassi, Pier Francesco; Pinto, Francesco

    2016-01-01

    Prostate cancer is the most common urologic neoplasm and the second leading cause of cancer-related death among men in many developed countries. Given the highly heterogeneous behaviour of the disease, there is a great need for prognostic factors, in order to stratify the clinical risk and give the best treatment options to the patient. Clinical factors, such as prostate-specific antigen value and derivatives, and pathological factors, such as stage and Gleason grading, are well kown prognostic factors. Nomograms can provide useful prediction in each clinical sceario. The field of molecular biomarkers is briskly evolving towards personalized medicine. TMPRSS2-ERG fusion, deletion of PTEN ed and gene panels are some of the more extensively explored molecular features in prostate cancer outcome prediction. In the near future, circulating tumour cells, exosomes and microRNAs could give us further, not invasive important tools. PMID:26917215

  10. Prognostic Value of Brain and Acute Leukemia Cytoplasmic Gene Expression in Egyptian Children with Acute Myeloid Leukemia

    PubMed Central

    Hagag, Adel A.; El-Lateef, Amal Ezzat Abd

    2015-01-01

    = 0.017). Conclusion and Recommendation BAALC expression is an important bad prognostic factor in AML patients with normal karyotype and therefore we recommend its incorporation into novel risk-adapted therapeutic strategies to improve the currently disappointing cure rate of patients with AML. PMID:25960861

  11. Microenvironmental remodeling as a parameter and prognostic factor of heterogeneous leukemogenesis in acute myelogenous leukemia.

    PubMed

    Kim, Jin-A; Shim, Jae-Seung; Lee, Ga-Young; Yim, Hyeon Woo; Kim, Tae-Min; Kim, Myungshin; Leem, Sun-Hee; Lee, Jong-Wook; Min, Chang-Ki; Oh, Il-Hoan

    2015-06-01

    Acute myelogenous leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of stem cell-like blasts in bone marrow (BM); however, their unique cellular interaction within the BM microenvironment and its functional significance remain unclear. Here, we assessed the BM microenvironment of AML patients and demonstrate that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells (MSC). The modified leukemic niche alters the expressions of cross-talk molecules (i.e., CXCL12 and JAG1) in MSCs to provide a distinct cross-talk between normal and leukemia cells, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemoresistance. Of note, AML patients exhibited distinct heterogeneity in the alteration of mesenchymal stroma in BM. The distinct pattern of stromal changes in leukemic BM at initial diagnosis was associated with a heterogeneous posttreatment clinical course with respect to the maintenance of complete remission for 5 to 8 years and early or late relapse. Thus, remodeling of mesenchymal niche by leukemia cells is an intrinsic self-reinforcing process of leukemogenesis that can be a parameter for the heterogeneity in the clinical course of leukemia and hence serve as a potential prognostic factor. PMID:25791383

  12. Prognostic factors in non-surgically treated sciatica: A systematic review

    PubMed Central

    2011-01-01

    Background When present sciatica is considered an obstacle to recovery in low back pain patients, yet evidence is limited regarding prognostic factors for persistent disability in this patient group. The aim of this study is to describe and summarise the evidence regarding prognostic factors for sciatica in non-surgically treated cohorts. Understanding the prognostic factors in sciatica and their relative importance may allow the identification of patients with particular risk factors who might benefit from early or specific types of treatment in order to optimise outcome. Methods A systematic literature search was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective cohort studies describing subjects with sciatica and measuring pain, disability or recovery outcomes were included. Studies of cohorts comprised entirely of surgically treated patients were excluded and mixed surgically and conservatively treated cohorts were included only if the results were analysed separately by treatment group or if the analysis was adjusted for treatment. Results Seven adequate or high quality eligible studies were identified. There were conflicting but mainly negative results regarding the influence of baseline pain severity, neurological deficit, nerve root tension signs, duration of symptoms and radiological findings on outcome. A number of factors including age, gender, smoking, previous history of sciatica and heaviness of work do not appear to influence outcome. In contrast to studies of low back pain and purely surgically treated sciatica cohorts, psychological factors were rarely investigated. Conclusions At present, the heterogeneity of the available studies makes it difficult to draw firm conclusions about sciatica prognosis, and highlights the need for further research for this group of patients. Large scale prospective studies of high methodological quality, using a well-defined, consistent definition of sciatica and investigating psychosocial

  13. Prognostic significance of the heterogenous expression of IgG Fc receptors in B-cell chronic lymphocytic leukemia.

    PubMed

    Schranz, V; Gráf, F

    1992-03-01

    Receptors for the Fc part of IgG (Fc gamma R) are expressed in three forms on peripheral blood lymphocytes. The presence of the releasable form (Fc gamma R(REL.)) as well as of the two nonreleasable forms with lower (Fc gamma R(LOW)) and higher (Fc gamma R(HIGH)) cellular avidity was correlated with survival in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL). High percentage of cells with Fc gamma R(LOW) as well as high "absolute" number of cells carrying the two nonreleasable forms of Fc gamma R were connected to unfavorable prognosis. Combining these three parameters, an Fc gamma R constellation was defined which pointed to a favorable prognosis (in 24 patients) when all three parameters were low, but detected short survivors when all three data were high (in 14 patients). The Fc gamma R constellation was capable of identifying patients with better or worse prognosis within groups that were homogeneous regarding some other known prognostic factors. Fc gamma R constellation as a prognostic factor was shown to be independent of age, sex, and Rai and Binet stages, but it was found to be connected with the total tumor mass score (TTM). The three forms of Fc gamma R on B cells might reflect stages of B-cell activation. Differences in Fc gamma R constellations between patients with B-CLL would thus correspond to differently activated B-cell clones with variable prognosis. PMID:1571409

  14. OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

    PubMed Central

    Weixler, Benjamin; Cremonesi, Eleonora; Sorge, Roberto; Muraro, Manuele Giuseppe; Delko, Tarik; Nebiker, Christian A.; Däster, Silvio; Governa, Valeria; Amicarella, Francesca; Soysal, Savas D.; Kettelhack, Christoph; von Holzen, Urs W.; Eppenberger-Castori, Serenella; Spagnoli, Giulio C.; Oertli, Daniel; Iezzi, Giandomenica; Terracciano, Luigi; Tornillo, Luigi

    2015-01-01

    Background OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. Methods OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. Results OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40high/CD8high infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40low/CD8high, OX40high/CD8low or OX40low/CD8low infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40high/CD8high density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. Conclusions OX40high/CD8high density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers. PMID:26439988

  15. HIF-1alpha Expression Profile in Intratumoral and Peritumoral Inflammatory Cells as a Prognostic Marker for Squamous Cell Carcinoma of the Oral Cavity

    PubMed Central

    Mendes, Suzanny Oliveira; dos Santos, Marcelo; Peterle, Gabriela Tonini; Maia, Lucas de Lima; Stur, Elaine; Agostini, Lidiane Pignaton; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Trivilin, Leonardo Oliveira; da Silva-Conforti, Adriana Madeira Álvares

    2014-01-01

    The HIF-1 transcriptional complex is responsible for controlling transcription of over 100 genes involved in cell hypoxia response. HIF-1alpha subunit is stabilized in hypoxia conditions, creating the HIF-1 nuclear transcription factor. In inflammatory cells, high HIF-1alpha expression induces lymphocytic immunosuppression, decreasing tumoral antigen recognition, which promotes tumor growth. The present work investigated the relationship between HIF-1alpha expression in lymphocytes populating the intratumoral and peritumoral region of 56 patients with oral cancer. Our data indicates a prognostic value for this expression. High HIF-1alpha expression in peritumoral inflammatory cells is significantly related to worse patient outcome, whereas high expression in the intratumoral lymphoid cells correlates with a better prognosis. A risk profile indicating the chance of disease relapse and death was designed based on HIF-1alpha expression in tumoral inflammatory cells, defining low, intermediate and high risks. This risk profile was able to determine that high HIF-1alpha expression in peritumoral cells correlates with worse prognosis, independently of intratumoral expression. Low HIF-1alpha in tumor margins and high expression in the tumor was considered a low risk profile, showing no cases of disease relapse and disease related death. Intermediate risk was associated with low expression in tumor and tumor margins. Our results suggest that HIF-1alpha expression in tumor and peritumoral inflammatory cells may play an important role as prognostic tumor marker. PMID:24416312

  16. Aberrant phenotypic expression of CD15 and CD56 identifies poor prognostic acute promyelocytic leukemia patients.

    PubMed

    Breccia, Massimo; De Propris, Maria Stefania; Minotti, Clara; Stefanizzi, Caterina; Raponi, Sara; Colafigli, Gioia; Latagliata, Roberto; Guarini, Anna; Foà, Robin

    2014-02-01

    Limited information is available on the relationship between expression of some additional aberrant phenotypic features and outcome of acute promyelocytic leukemia (APL) patients. Here, we set out to assess the frequency of CD15 and CD56 expression, and their prognostic value in a large series of APL patients. One hundred and fourteen adult patients consecutively diagnosed with PML/RARα-positive APL and homogeneously treated with the AIDA induction schedule at a single institution were included in the study. Twelve (10.5%) and 9 (8%) of the 114 patients expressed CD15 and CD56, respectively. CD15 expression identified a subset of patients with a classic morphologic subtype (92%), a prevalent association with a bcr1 expression (67%) with an unexpectedly higher frequency of relapses (42% vs 20% for the CD15- patients, p=0.03) and a low overall survival (OS) (median OS at 5 years 58% vs 85% for the CD15- patients, p=0.01). CD56 expression was detected only in patients with a classic morphologic subtype, a prevalent bcr3 expression (67%), high incidence of differentiation syndrome (55%), higher frequency of relapse (34% vs 20% for the CD56- population, p=0.04) and a low OS (60% vs 85% for the CD56- population p=0.02). We hereby confirm the negative prognostic value of CD56 and we show that the same applies also to cases expressing CD15. These aberrant markers may be considered for the refinement of risk-adapted therapeutic strategies in APL patients. PMID:24296270

  17. Prognostic Value of Osteopontin Splice Variant-c Expression in Breast Cancers: A Meta-Analysis

    PubMed Central

    Hao, Chengcheng; Wang, Zhiyan; Gu, Yanan; Jiang, Wen G.

    2016-01-01

    Objectives. Osteopontin (OPN) is overexpressed in breast cancers, while its clinical and prognostic significance remained unclear. This study aimed to assess the prognostic value of OPN, especially its splice variants, in breast cancers. Methods. Data were extracted from eligible studies concerning the OPN and OPN-c expression in breast cancer patients and were used to calculate the association between OPN/OPN-c and survival. Two reviewer teams independently screened the literatures according to the inclusion and exclusion criteria based on quality evaluation. Following the processes of data extraction, assessment, and transformation, meta-analysis was carried out via RevMan 5.3 software. Results. A total of ten studies involving 1,567 patients were included. The results demonstrated that high level OPN indicated a poor outcome in the OS (HR = 2.22, 95% CI: 1.23–4.00, and P = 0.008; random-effects model) with heterogeneity (I2 = 62%) of breast cancer patients. High level OPN-c appeared to be more significantly associated with poor survival (HR = 2.14, 95% CI: 1.51–3.04, and P < 0.0001; fixed-effects model) with undetected heterogeneity (I2 = 0%). Conclusions. Our analyses indicated that both OPN and OPN-c could be considered as prognostic markers for breast cancers. The high level of OPN-c was suggested to be more reliably associated with poor survival in breast cancer patients. PMID:27462610

  18. Prognostic role of YB-1 expression in breast cancer: a meta-analysis

    PubMed Central

    Wang, Xu; Guo, Xiao-Bo; Shen, Xiao-Chun; Zhou, Hao; Wan, Dan-Wei; Xue, Xiao-Feng; Han, Ye; Yuan, Bin; Zhou, Jin; Zhao, Hong; Zhi, Qiao-Ming; Kuang, Yu-Ting

    2015-01-01

    Objective: In published studies, Y-box binding protein-1 (YB-1) correlated with the prognosis of patients with breast cancer (BC), but the specific role of YB-1 is still unclear. Our study aimed to evaluate the prognostic value of YB-1 in BC patients using meta-analysis based on the published studies. Methods: We searched the relevant literatures deadline for June 2014 in databases, including PubMed, Embase, Medline and Cochrane library, and finally 8 studies were included in our study. Our study contained 1094 BC patients with 398 YB-1 positive and 696 YB-1 negative. Results: Our results showed that YB-1 abnormal expression did not correlated with the lymph node status [OR = 1.258, 95% CI = 0.895-1.769, P = 0.186], high histological grade [OR = 2.709, 95% CI = 0.861-8.530, P = 0.089], histological type [OR = 0.837, 95% CI = 0.526-1.331, P = 0.452], P53 status [OR = 2.006, 95% CI 0.686-5.865, P = 0.203] and PR [OR = 0.607, 95% CI = 0.347-1.061, P = 0.080] in BC patients. But YB-1 over-expression was associated with other unfavorable factors: ER negativity [OR = 0.604, 95% CI = 0.388-0.941, P = 0.026], HER2 positivity [OR = 3.841, 95% CI = 2.637-5.594, P = 0.000], and high tumorous T stage [OR = 2.169, 95% CI = 1.295-3.632, P = 0.003]. In addition, our data suggested that high YB-1 expression had an adverse impact on 5-year OS [RR = 2.767, 95% CI = 2.054-3.727, P = 0.000] in BC patients. Conclusions: Our findings implied that YB-1 might a novel biomarker to predict the prognosis of BC, and could be a potential direction for developing diagnostic and therapeutic approaches in BC. PMID:25932106

  19. Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

    PubMed

    Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-01-01

    Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients. PMID:26634475

  20. Malignant myelomatous pleural effusion-Is onset of effusion a new prognostic factor?

    PubMed

    Attili, Suresh; Ullas, Batra; Lakshm, Devi; Bapsy, P P; Lakshm, K C; Govind, K; Lokana, D; Kamal, Saini; Anupam, G

    2007-12-01

    Malignant pleural effusion in myeloma (MMPE) is a rare terminal event; with a median survival is four months. All the patients usually have multiple poor prognostic factors and none of them (like beta 2-microglobulin, karyotype, Stage of disease, C-reactive protein etc.) correctly predicts the survival. We are reporting a series of five cases and evaluated the factors influencing the overall survival. All of our patients had a very good response to treatment and had a better survival compared to the reported cases so far. After reviewing the literature carefully we found that timing of development of pleural effusion is probably the most important prognostic factor. Those who develop effusion after some time lag form the initial treatment, will have a poor survival (median four months) compared to those who had effusion at the start of the disease. PMID:27263959

  1. Prognostic Significance of Nuclear β-Catenin Expression in Patients with Colorectal Cancer from Iran

    PubMed Central

    Nazemalhosseini Mojarad, Ehsan; Kashfi, Seyed Mohammad Hossein; Mirtalebi, Hanieh; Almasi, Shohre; Chaleshi, Vahid; Kishani Farahani, Roya; Tarban, Peyman; Molaei, Mahsa; Zali, Mohammad Reza; J.K. Kuppen, Peter

    2015-01-01

    Background: Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/β-catenin pathway. Accumulation of nuclear β-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear β-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC. Objectives: In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated. Patients and Methods: In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear β-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant. Results: The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of β-catenin and 133 (80.6 %) were negative for β-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear β-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear β-catenin positive expression

  2. Seeking new prognostic and predictive factors in patients with metastatic renal cell carcinoma – apoptosis-regulating factors

    PubMed Central

    Szczylik, Cezary; Rzepecki, Piotr

    2012-01-01

    Kidney cancer, despite the constant upward trend in the incidence of this type of cancer (about 1.5-5.9% per year), is rather rare, representing approximately 2-3% of all adult cancers. Since recently, drugs based on so-called targeted therapy play a decisive role in the treatment of patients with metastatic kidney cancer. Prognostic and predictive factors can significantly contribute to prognosis assessment and the correct classification of patients to specific forms of causal treatment of kidney cancer. In addition to the most commonly used and widely known prognostic factors, grouped in the so-called Motzer model, new prognostic markers of this tumour are being sought. Preliminary reports indicate that there may be a promising role of factors that regulate the cell cycle and apoptosis, and agents from the group of hypoxia-induced proteins. The proliferation markers or proteins related to cellular adhesion can also be relevant. This article presents examples of markers from the first of the above groups of proteins, which on the basis of the performed analyses showed independent prognostic or predictive value in kidney cancer. PMID:23788861

  3. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    SciTech Connect

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  4. ARID1A expression in early stage colorectal adenocarcinoma: an exploration of its prognostic significance.

    PubMed

    Lee, Lik Hang; Sadot, Eran; Ivelja, Sinisa; Vakiani, Efsevia; Hechtman, Jaclyn F; Sevinsky, Christopher J; Klimstra, David S; Ginty, Fiona; Shia, Jinru

    2016-07-01

    ARID1A is a chromatin remodeling gene that is mutated in a number of cancers including colorectal carcinoma (CRC). Loss of ARID1A has been associated with an adverse outcome in some types of cancer. However, literature data have not been consistent. Major limitations of some outcome studies include small sample size and heterogeneous patient population. In this study, we evaluated the prognostic value of ARID1A in a homogeneous group of early stage CRC patients, a population where prognostic markers are particularly relevant. We collected a retrospective series of 578 stage I or II CRCs. All patients underwent surgery with curative intent and without neoadjuvant or adjuvant therapy. ARID1A expression was analyzed by immunohistochemistry using tissue microarray. We found ARID1A loss in 49 of 552 analyzable tumors (8.9%). Compared with the ARID1A-retained group, cases with ARID1A loss were associated with female sex (P<.001), mismatch-repair protein deficiency (P<.001), poor differentiation (P<.001), lymphovascular invasion (P=.001), and higher pT stage (P=.047). However, at a median follow-up of 49months, ARID1A loss did not correlate with overall, disease-specific, or recurrence-free survival. This is the first systematic analysis to evaluate the prognostic significance of ARID1A in stage I/II CRCs, and our data indicate that ARID1A loss lacks prognostic significance in this population despite its association with other adverse features. Such data are clinically relevant, as efforts are ongoing in identifying markers that can detect the small but significant subset of early stage CRCs that will have a poor outcome. PMID:26980037

  5. The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts.

    PubMed

    Aleskandarany, Mohammed A; Agarwal, Devika; Negm, Ola H; Ball, Graham; Elmouna, Ahmed; Ashankyty, Ibraheem; Nuglozeh, Edem; Fazaludeen, Mohammad F; Diez-Rodriguez, Maria; Nolan, Christopher C; Tighe, Patrick J; Green, Andrew R; Ellis, Ian O; Rakha, Emad A

    2016-02-01

    Signal transducer and activator of transcription (STAT) transcription factors family are involved in diverse cellular biological functions. Reports regarding the prognostic impact of STAT3 expression in breast cancer (BC) are variable whether being a factor of poor or good prognosis. Immunohistochemical expression of phospho-STAT3 (pSTAT3) was studied in large series of invasive BC (n = 1270). pSTAT3 and STAT3 were quantified using reverse phase protein array (RPPA) on proteins extracted from macro-dissected FFPE tissues (n = 49 cases). STAT3 gene expression in the METABRIC cohort was also investigated. STAT3 gene expression prognostic impact was externally validated using the online BC gene expression data (n = 26 datasets, 4.177 patients). pSTAT3 was expressed in the nuclei and cytoplasm of invasive BC cells. Nuclear pSTAT3 overexpression was positively associated with smaller tumour size, lower grade, good NPI, negative lymphovascular invasion (LVI), ER+, PgR+, p53-, HER2-, and low Ki67LI and an improved breast cancer-specific survival (BCSS), independently of other factors. On RPPA, the mean pSTAT3 and STAT3 expressions were higher in ER+, PgR+, and smaller size tumours. Higher STAT3 transcripts in the METABRIC cohort were observed in cases with favourable prognostic criteria and as well as improved BCSS within the whole cohort, ER+ cohort with and without hormonal therapy, and ER- cohort including those who did not receive adjuvant chemotherapy. Pooled STAT3 gene expression data in the external validation cohort showed an association with improved patients' outcome (P < 0.001, HR = 0.84, 95 % CI 0.79-0.90). Results of this study suggest nuclear localisation of pSTAT3 as favourable prognostic marker in invasive BC, results re-enforced by analysis of STAT3 gene expression data. This good prognostic advantage was maintained in patients who received and who did not receive adjuvant therapy. Therefore, STAT3 could have context-dependent molecular roles of in BC

  6. Adjuvant radiochemotherapy for gastric cancer: Should we use prognostic factors to select patients?

    PubMed

    Agolli, Linda; Maurizi Enrici, Riccardo; Osti, Mattia Falchetto

    2016-01-21

    Radiotherapy has a not well-established role in the pre-operative and in the post-operative setting in gastric cancer (GC) patients. Randomized trials report controversial outcomes and impact on survival. In the D2 loco-regional node resection era, after a well-performed radical surgery, local treatment using radiotherapy combined to chemotherapy should be considered for locally advanced GC. Prognostic factors could help the better selection of subgroups that present high risk of loco-regional recurrence. Then, the addition of radiotherapy could improve the disease-free survival and also quality of life. There are no large prospective studies that have assessed specific factors predicting for recurrence or survival, but only retrospective series, some of them including high number of patients with homogeneous characteristics. In locally advanced GC adding radiotherapy to the post-operative chemotherapy seems to improve outcomes and quality of life. Prognostic factors such as T-stage, N-status, nodal ratio, and other histological factors should be considered to submit patients to post-operative combined treatment. Larger prospective series are necessary to investigate the role of combined chemoradiation after radical D2-resection, especially in locally advanced GC. Further prospective investigations are needed to suggest prognostic factors that have significant impact on survival and recurrence, improving the management and outcomes, particularly in locally advanced GC patients. PMID:26811652

  7. Diffuse large B-cell lymphoma of the breast: prognostic factors and treatment outcomes

    PubMed Central

    Sun, Yao; Joks, Monika; Xu, Li-Ming; Chen, Xiu-Li; Qian, Dong; You, Jin-Qiang; Yuan, Zhi-Yong

    2016-01-01

    Background The breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL). We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL. Patients and methods We retrospectively analyzed 113 patients (from our institution and the literature) between 1973 and 2014. The primary end point was overall survival (OS). Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS), local control (LC), and cause-specific survival (CSS). Results A total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN) dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size >4 cm and nonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6%) developed local relapse and 33 (29.2%) developed systemic relapse. Eight patients had central nervous system relapse (7.3%). Conclusion Our results reveal that local and extended staging criteria can reflect the different prognosis and treatment outcomes of breast DLBCL. Rituximab use, lumpectomy, and more than four cycles of chemotherapy are recommended as a treatment regimen. However, further study is warranted to validate our data. PMID:27103833

  8. Integrin α5 promotes tumor progression and is an independent unfavorable prognostic factor in esophageal squamous cell carcinoma.

    PubMed

    Xie, Jian-Jun; Guo, Jin-Cheng; Wu, Zhi-Yong; Xu, Xiu-E; Wu, Jian-Yi; Chen, Bo; Ran, Li-Qiang; Liao, Lian-Di; Li, En-Min; Xu, Li-Yan

    2016-02-01

    The integrin family plays a major role in complex biological events such as differentiation, development, wound healing, and the altered adhesive and invasive properties of tumor cells. The expression and function of integrin α5 in esophageal squamous cell carcinoma (ESCC) are not clear. Here, by using tissue microarrays and immunohistochemical method, integrin α5 expression was retrospectively evaluated in 147 samples of human ESCC. Results showed that expression of integrin α5 was heterogeneous and varied from negative to intense expression in a membrane and cytoplasmic distribution manner. High expression of integrin α5 was significantly correlated with lymph node metastasis (P = .042) and tumor size (P = .042). Kaplan-Meier analysis revealed that high expression of integrin α5 was related to poor overall survival of ESCC patients (P = .018). Multivariate analysis suggested that integrin α5 expression status was an independent prognostic factor for ESCC (P = .003). Moreover, integrin α5 expression was associated with the survival of patients with lymph node metastasis (P = .020), but did not influence the survival of patients without lymph node metastasis. Finally, we found that RNAi-mediated knockdown of integrin α5 led to decreased growth, migration, and invasion of ESCC cells. Combined, integrin α5 might play important roles in the progression of ESCC. Integrin α5 is a novel biomarker to predict the prognosis of ESCC patients. PMID:26772401

  9. MicroRNA 141 Expression Is a Potential Prognostic Marker of Biliary Tract Cancers

    PubMed Central

    Kim, Jaihwan; Ryu, Ji Kon; Lee, Sang Hyub; Kim, Yong-Tae

    2016-01-01

    Background/Aims In recent years, a large number of micro-ribonucleic acids (miRNAs) have been identified as putative prognostic biomarkers for solid cancers because of their role in controlling the expression of oncogenes and tumor suppressor genes. The aim of this study was to verify the utility of miRNA 141 as a prognostic biomarker of biliary tract cancers. Methods From June 2010 to June 2012, common bile duct cancer tissue samples and matched noncancerous tissues from the ampulla of Vater were obtained from patients with biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography. Using quantitative real-time polymerase chain reaction assays, we measured the mean relative expression levels of miRNA 141 in both groups of tissues. Overexpression of miRNA 141 was defined as a greater than 2-fold increase in expression levels as determined by the 2−ΔΔCt method. Results In a cohort of 38 patients with biliary tract cancers (seven gallbladder, 13 hilar, and 18 distal bile duct cancers), 26 patients (68.4%) were male, and the median age was 69.5 (52 to 85) years. Nineteen patients (50%) had undergone R0 resection procedures, including three Whipple operations, seven pylorus-preserving pancreaticoduodenectomies, six bile duct resections, and three extended lobectomies. Among the patients who had undergone R0 resection, the overexpression of miRNA 141 was significantly associated with shorter disease-free survival and a greater risk of angiolymphatic invasion. Among the patients who did not undergo R0 resection, miRNA 141 overexpression was significantly associated with reduced overall survival. Conclusions Overexpression of miRNA 141 is an indicator of a poor prognosis in patients with biliary tract cancer, suggesting that miRNA 141 may be a valuable prognostic biomarker of this disease. PMID:27172928

  10. Prognostic significance of PD-L1 expression in patients with gastric cancer in East Asia: a meta-analysis

    PubMed Central

    Liu, Yong-Xuan; Wang, Xin-Shuai; Wang, Yu-Feng; Hu, Xiao-Chen; Yan, Jun-Qiang; Zhang, Ya-Li; Wang, Wei; Yang, Rui-Jie; Feng, Ying-Ying; Gao, She-Gan; Feng, Xiao-Shan

    2016-01-01

    The overexpression of programmed cell death-ligand 1(PD-L1) has been observed in gastric cancer (GC). However, whether the expression of PD-L1 in tumor cells or blood serum is associated with the prognosis of patients with GC remains unclear. Therefore, we performed a meta-analysis to evaluate the prognostic significance of PD-L1 expression in GC. Electronic databases were searched systematically. Studies that met the inclusion criteria were included in the meta-analysis. Data concerning the hazard ratio (HR) for overall survival and disease-free survival with a 95% confidence interval (CI) according to the expression status of PD-L1 evaluated by immunohistochemistry or enzyme-linked immunosorbent assay were extracted. The data were analyzed using a random effects model. Subgroup analyses were proposed. Our results showed that eight studies with 950 patients met the inclusion criteria and were included in the meta-analysis. The pooled HR for overall survival indicated that patients with PD-L1-positive expression had significantly shorter survival time compared with the PD-L1-negative group (HR 1.60, 95% CI 1.09–2.36, P=0.012). The pooled HR for disease-free survival demonstrated that the difference between the two groups was not statistically significant (HR 1.02, 95% CI 0.32–3.20, P=0.98). In conclusion, our results indicate that the evaluation of PD-L1 overexpression in GC tissue or blood serum may be useful in the future as a novel prognostic factor. PMID:27226727

  11. Prognostic Impact of mRNA Expression Levels of HER1–4 (ERBB1–4) in Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Kripp, Melanie; Merx, Kirsten; Wirtz, Ralph Markus; Gaiser, Timo; Eidt, Sebastian; Schwaab, Juliana; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas

    2016-01-01

    Background. No predictive or prognostic biomarker is available for patients with locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy (CRT). Members of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was performed to assess expression levels and study the potential prognostic impact for disease-free and overall survival in patients with LARC. Patients and Methods. ERBB1–4 mRNA expression and tumor proliferation using Ki-67 (MKI67) mRNA were evaluated using RT-quantitative PCR in paraffin-embedded tumor samples from 86 patients (median age: 63) treated with capecitabine or 5-fluorouracil-based CRT within a phase 3 clinical trial. Results. A positive correlation of HER4 and HER2, HER3 and HER2, and HER4 and HER3 with each other was observed. Patients with high mRNA expression of ERBB1 (EGFR, HER1) had significantly increased risk for recurrence and death. Patients with high mRNA expression of MKI67 had reduced risk for relapse. Conclusion. This analysis suggests a prognostic impact of both ERBB1 and MKi67 mRNA expression in LARC patients treated with capecitabine or fluorouracil-based chemoradiotherapy. PMID:27610130

  12. Immunohistochemical Expression and Prognostic Significance of CD97 and its Ligand DAF in Human Cervical Squamous Cell Carcinoma.

    PubMed

    He, Ying; Wang, Wei; Xu, Lian; Li, Li; Liu, Juan; Feng, Min; Bu, Hong

    2015-09-01

    Accumulating evidences had demonstrated that the CD97, a member of the epidermal growth factor 7-transmembrane family, and its cellular ligand decay accelerating factor (DAF) both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. However, the roles of CD97 and DAF in human cervical squamous cell carcinoma (CSCC) have not been investigated. The purpose of this study was to observe the expression profile of CD97 and DAF in CSCC and evaluate their clinical significance. Immunohistochemistry was used to investigate the expression of CD97 and DAF proteins in 97 patients with CSCC and 53 patients with cervical intraepithelial neoplasia, a precursor lesion of CSCC. CD97 and DAF were absent or only weakly expressed in the normal epithelium of the cervix but were present in 83.5% (81/97) and 90.7% (88/97) of CSCC samples, respectively. Overexpression of CD97 was significantly associated with a high International Federation of Gynecology and Obstetrics stage (P=0.010) and lymph node metastasis (P=0.026). The majority of CSCCs, irrespective of staging/grading classification, displayed strong DAF immunostaining. Kaplan-Meier survival analysis revealed that overexpression of CD97 was associated with a worse prognosis. Multivariate analyses showed that the International Federation of Gynecology and Obstetrics stage (P=0.000), lymph node metastasis (P=0.004), and CD97 expression (P=0.040) were independent risk factors for overall survival. The present study suggested that the expressions of CD97 and DAF were both upregulated in CSCC. The expression level of CD97 in CSCC was associated with the severity of the tumor. Furthermore, CD97 might be an independent poor prognostic factor for CSCC patients. PMID:26107567

  13. Prognostic factors on survival rate of fingers replantation

    PubMed Central

    Lima, José Queiroz; Carli, Alberto De; Nakamoto, Hugo Alberto; Bersani, Gustavo; Crepaldi, Bruno Eiras; de Rezende, Marcelo Rosa

    2015-01-01

    Objective: To evaluate the factors that influence the survival rate of replantation and revascularization of the thumb and/or fingers. Methods: We included fifty cases treated in our department from May 2012 to October 2013 with total or partial finger amputations, which had blood perfusion deficit and underwent vascular anastomosis. The parameters evaluated were: age, gender, comorbidities, trauma, time and type of ischemia, mechanism, the injured area, number of anastomosed vessels and use of vein grafts. The results were statistically analyzed and type I error value was set at p <0.05 . Results: Fifty four percent of the 50 performed replantation survived. Of 15 revascularizations performed, the survival rate was 93.3%. The only factor that affected the survival of the amputated limb was the necessity of venous anastomosis. Conclusion: We could not establish contraindications or absolute indications for the replantation and revascularization of finger amputations in this study. Level of Evidence III, Retropective Study. PMID:26327788

  14. Predicting prognostic factors of breast cancer using shear wave elastography.

    PubMed

    Choi, Woo Jung; Kim, Hak Hee; Cha, Joo Hee; Shin, Hee Jung; Kim, Hyunji; Chae, Eun Young; Hong, Min Ji

    2014-02-01

    The purpose of the study described here was to investigate the correlation between histologic factors, including immunohistochemical factors, related to the prognosis of breast cancer and shear wave elastography (SWE) measurements. One hundred twenty-two breast cancers from 116 women were subjected to sonoelastography. Of the SWE features, mean and maximum elasticity and SWE ratio were extracted. The SWE ratio was calculated as the ratio of the stiffness of a portion of the lesion to that of a similar region of interest in fatty tissue. High ratios indicate stiffer lesions. The Mann-Whitney U-test, Kruskal-Wallis test and receiver operating characteristic (ROC) curve were used for statistical analysis. Estrogen receptor negativity, progesterone receptor negativity, p53 positivity, Ki-67 positivity, high nuclear grade, high histologic grade and large tumor (invasive) size were associated with a significantly high SWE ratio (p < 0.05). ROC curve analysis yielded SWE ratio cutoff values of 2.74-3.69 for significant immunohistochemical factors and 4.21 for the basal-like subtype by maximizing specificity while ensuring more than 80% sensitivity. Breast cancers with aggressive histologic features had high SWE ratios. Shear wave elastography may provide useful information for determining prognosis. PMID:24268451

  15. The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma

    PubMed Central

    Nota, Sjoerd P. F. T.; Braun, Yvonne; Schwab, Joseph H.; van Dijk, C. Niek; Bramer, Jos A. M.

    2015-01-01

    Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma. Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients. Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival. Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients. PMID:26633939

  16. The Association between EGFR and cMET Expression and Phosphorylation and Its Prognostic Implication in Patients with Breast Cancer

    PubMed Central

    Chae, Young Kwang; Gagliato, Debora de Melo; Pai, Sachin Gopalkrishna; Carneiro, Benedito; Mohindra, Nisha; Giles, Francis Joseph; Ramakrishnan-Geethakumari, Praveen; Sohn, Joohyuk; Liu, Shuying; Chen, Huiqin; Ueno, Naoto; Hortobagyi, Gabriel; Gonzalez-Angulo, Ana Maria

    2016-01-01

    EGFR and cMET cross-talk is involved in breast cancer (BC) progression and resistance to different targeted therapies, however little is known about the co-expression patterns of EGFR and cMET or its prognostic significance in BC. Protein levels of EGFR, cMET and their phosphorylated proteins were measured in 825 BC samples using reverse phase protein array (RPPA). Given unimodal distribution of proteins, the median was selected as a cut-off after sensitivity analyses. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall survival (OS). Cox-proportional hazards models were utilized to determine associations between EGFR and cMET with outcomes. Mean age was 58 years with 457 (55%) hormone receptor (HR) positive, 211 (26%) triple-negative (TN) and 148 (18%) HER2 positive tumors (HER2+). HER2+ was associated with higher EGFR expression and phosphorylation, compared to HR and TN (p<0.05). High EGFR expression was associated with higher phosphorylated-cMET (p-cMET) but not cMET (ANOVA p-cMET p < 0.001; cMET p = 0.34). The same association was found with high phosphorylated-EGFR (p-EGFR) group at Tyr992 and Tyr1068 (both p < 0.001). High expressions in either of two p-EGFRs were linked with higher cMET as well (all p<0.001). For the TN subtype, high expression in EGFR and p-EGFR at Tyr992 but not at Tyr1068 was associated with higher p-cMET (p<0.00, p = 0.012, p = 0.4 respectively). Only high expression in p-EGFR at Tyr992 was linked with higher expression of cMET (p = 0.02). In contrast, among HER2 subtype, high expression in p-EGFR at Tyr1068 but not at Tyr992 was associated with higher cMET and p-cMET (cMET p = 0.023;p-cMET p<0.001). Four subgroups of patients defined by dichotomized EGFR/p-EGFR and cMET/p-cMET level demonstrated no significant differences in survival. In multivariate analyses, neither cMET nor EGFR expression/activation was found to be an independent prognostic factor in survival outcome. PMID:27055285

  17. Acute Liver Failure in Pregnancy: Causative and Prognostic Factors

    PubMed Central

    Sahai, Shweta; Kiran, Ravi

    2015-01-01

    Background/Aims: Acute liver failure (ALF) in pregnancy is often associated with a poor prognosis. In this single-center observational study we aim to study the incidence, causes, and factors affecting mortality in pregnant women with ALF. Patients and Methods: Sixty-eight pregnant women reporting with clinical features of liver dysfunction were enrolled as cases. Their clinical course was followed and laboratory studies were performed. The presence of ALF was defined as the appearance of encephalopathy. The results were compared with a control group of 16 nonpregnant women presenting with similar complaints. The cases were further subdivided into two groups of survivors and nonsurvivors and were compared to find out the factors that contribute to mortality. Results: ALF was seen in significantly more number of pregnant women than the controls (P = 0.0019). The mortality rate was also significantly higher (P = 0.0287). Hepatitis E virus (HEV) caused jaundice in a higher number of pregnant women (P < 0.001). It also caused ALF in majority (70.3%) of pregnant women, but HEV infection was comparable between the survivors and nonsurvivors (P = 0.0668), hence could not be correlated with mortality. Conclusions: Pregnant women appear to be more susceptible for HEV infection and development of ALF. The mortality of jaundiced pregnant women increased significantly with appearance of ALF, higher bilirubin, lower platelet count, higher international normalized ratio, and spontaneous delivery. PMID:25672236

  18. Prognostic value of decreased expression of RBM4 in human gastric cancer

    PubMed Central

    Yong, Hongmei; Zhu, Huijun; Zhang, Shu; Zhao, Wei; Wang, Wei; Chen, Chen; Ding, Guipeng; Zhu, Lun; Zhu, Ziyuan; Liu, Huaidong; Zhang, Yongjie; Wen, Jinbo; Kang, Xing; Zhu, Jin; Feng, Zhenqing; Liu, Baorui

    2016-01-01

    RNA-binding motif 4 (RBM4) is a multifunctional protein that participates in regulating alternative splicing and mRNA translation. Its reduced expression has been associated with poor overall survival in lung cancer, breast cancer and ovarian cancer. We assessed RBM4 protein expression levels with immunohistochemistry in tissue microarrays containing malignant gastric cancer tissues and benign tissues from 813 patients. We also examined the expression levels of RBM4 mRNA in twenty-five paired gastric cancer samples and adjacent noncancerous tissues. Both RBM4 protein and mRNA expression levels were significantly lower in gastric cancer tissues compared with the adjacent noncancerous tissues. There was a significant association between reduced RBM4 protein expression and differentiation (P < 0.001), lymph node metastasis (P = 0.026), TNM state (P = 0.014) and distant metastasis (P = 0.036). Patients with reduced RBM4 expression (P < 0.001, CI = 0.315–0.710) and TNM stage III and IV (P < 0.001, CI = 4.757–11.166) had a poor overall survival. These findings suggest that RBM4 is a new biomarker in gastric cancer, as the reduced expression of this protein is correlated with poor differentiation, lymph node status and distant metastasis. Further, lower RBM4 expression is an independent prognostic marker for gastric cancer. PMID:27324405

  19. Etiologies and prognostic factors of leukocytoclastic vasculitis with skin involvement

    PubMed Central

    Bouiller, Kévin; Audia, Sylvain; Devilliers, Hervé; Collet, Evelyne; Aubriot, Marie Hélène; Leguy-Seguin, Vanessa; Berthier, Sabine; Bonniaud, Philippe; Chavanet, Pascal; Besancenot, Jean-François; Vabres, Pierre; Martin, Laurent; Samson, Maxime; Bonnotte, Bernard

    2016-01-01

    Abstract In this study, outcomes of patients with leukocytoclastic vasculitis (LCV) were analyzed focusing on clinical, histopathology and laboratory findings, relapses, and survival. Data from patients with cutaneous vasculitis diagnosed between January 1, 2000, and December 31, 2010, at Dijon University Hospital (France) were retrospectively reviewed. LCV was defined as perivascular neutrophilic infiltrate, endothelial cell nuclear swelling, extravasation of red blood cells, and/or fibrin deposition in vessels. Patients were classified according to the 2012 Chapel Hill Consensus Conference. Relapses were defined as the recurrence of vasculitis symptoms after a period of remission >1 month. Time to relapse and/or death was calculated from the date of diagnosis. Univariate and multivariate (Cox model) analyses were performed. A total of 112 patients (57 males and 55 females), with a mean age of 60 ± 19 (18–98) years, were analyzed. Overall follow-up was 61 ± 38 months. At diagnosis, all patients had skin lesions, purpura being the most common (n = 83). Lesions were associated with systemic involvement in 55 (51%) patients. Only 41 (36.6%) patients received specific treatment: glucocorticoids in 29 of 41 (70.7%) and immunosuppressants in 9 of 41 (22%). Sixty-two patients (55%) had LCV due to underlying causes, 29 (25.9%) had single-organ cutaneous small vessel vasculitis (SoCSVV), and 21 (18.8%) had unclassifiable LCV. Twenty patients of the cohort (18%) experienced relapse, 14 ± 13 (1–40) months after the diagnosis of LCV. None of the 29 patients with SoCSVV relapsed. Independent risk factors for relapse were vascular thrombosis in the biopsy [hazard ratio (HR) = 4.9; P = 0.017], peripheral neuropathy (HR = 9.8; P = 0.001), hepatitis (HR = 3.1; P = 0.004), and positive antineutrophil cytoplasm antibodies (ANCA, HR = 5.9 P = 0.005). In contrast, SoCSVV was a protective factor for relapse (HR = 0.12; P = 0.043). The 1-, 3-, and 6-year overall

  20. Prognostic factors of tumor recurrence in completely resected non-small cell lung cancer

    PubMed Central

    Tantraworasin, Apichat; Saeteng, Somcharoen; Lertprasertsuke, Nirush; Arreyakajohn, Nuttapon; Kasemsarn, Choosak; Patumanond, Jayanton

    2013-01-01

    Background Patients with completely resected non-small cell lung cancer (NSCLC) have an excellent outcome; however tumor recurs in 30%–77% of patients. This study retrospectively analyzed the clinicopathologic features of patients with any operable stage of NSCLC to identify the prognostic factors that influence tumor recurrence, including intratumoral blood vessel invasion (IVI), tumor size, tumor necrosis, and intratumoral lymphatic invasion. Methods From January 2002 to December 2011, 227 consecutive patients were enrolled in this study. They were divided into two groups: the “no recurrence” group and the “recurrence” group. Recurrence-free survival was analyzed by multivariable Cox regression analysis, stratified by tumor staging, chemotherapy, and nodal involvement. Results IVI, tumor necrosis, tumor diameter more than 5 cm, and nodal involvement were identified as independent prognostic factors of tumor recurrence. The hazard ratio (HR) of patients with IVI was 2.1 times higher than that of patients without IVI (95% confident interval [CI]: 1.4–3.2) (P = 0.001).The HR of patients with tumor necrosis was 2.1 times higher than that of patients without tumor necrosis (95% CI: 1.3–3.4) (P = 0.001). Patients who had a maximum tumor diameter greater than 5 cm had significantly higher risk of recurrence than patients who had a maximum tumor diameter of less than 5 cm (HR 1.9, 95% CI: 1.0–3.5) (P = 0.033). Conclusion IVI, tumor diameter more than 5 cm, and tumor necrosis are prognostic factors of tumor recurrence in completely resected NSCLC. Therefore, NSCLC patients, with or without nodal involvement, who have one or more prognostic factors of tumor recurrence may benefit from adjuvant chemotherapy for prevention of tumor recurrence. PMID:23785244

  1. Prognostic factors in the rehabilitation of patients with spinal problems

    PubMed Central

    Richardson, Alan E.; Tupper, Annemarie D.

    1975-01-01

    One hundred patients undergoing intensive rehabilitation for painful spinal lesions were studied. They were divided into three groups in relation to result, these being ‘good’, ‘moderate’ or ‘poor’. Seventy-eight per cent were regarded as ‘good’ or ‘moderate’. The ‘poor’ group showed significantly raised neuroticism scores measured by the Middlesex Hospital Questionnaire, particularly sub-scores for ‘depression’ and ‘somatic concomitants of anxiety’ in women and ‘free floating anxiety’, ‘depression’ and ‘obsessionality’ in men. Other factors associated with poor outcome were long history, multiple operations and a nonspecific diagnosis of ‘low back pain’. It is suggested that this group can be identified early and might benefit from a combined physical rehabilitation and psychotherapy programme. A controlled study to test this is planned.

  2. Therapeutic Outcomes and Prognostic Factors in Childhood Absence Epilepsy

    PubMed Central

    Kim, Hye Ryun; Kim, Gun-Ha; Eun, So-Hee; Eun, Baik-Lin

    2016-01-01

    Background and Purpose Childhood absence epilepsy (CAE) is one of the most common types of pediatric epilepsy. It is generally treated with ethosuximide (ESM), valproic acid (VPA), or lamotrigine (LTG), but the efficacy and adverse effects of these drugs remain controversial. This study compared initial therapy treatment outcomes, including VPA-LTG combination, and assessed clinical factors that may predict treatment response and prognosis. Methods Sixty-seven patients with typical CAE were retrospectively enrolled at the Korea University Medical Center. We reviewed patients' clinical characteristics, including age of seizure onset, seizure-free interval, duration of seizure-free period, freedom from treatment failure, breakthrough seizures frequency, and electroencephalogram (EEG) findings. Results The age at seizure onset was 7.9±2.7 years (mean±SD), and follow-up duration was 4.4±3.7 years. Initially, 22 children were treated with ESM (32.8%), 23 with VPA (34.3%), 14 with LTG (20.9%), and 8 with VPA-LTG combination (11.9%). After 48 months of therapy, the rate of freedom from treatment failure was significantly higher for the VPA-LTG combination therapy than in the three monotherapy groups (p=0.012). The treatment dose administrated in the VPA-LTG combination group was less than that in the VPA and LTG monotherapy groups. The shorter interval to loss of 3-Hz spike-and-wave complexes and the presence of occipital intermittent rhythmic delta activity on EEG were significant factors predicting good treatment response. Conclusions This study showed that low-dose VPA-LTG combination therapy has a good efficacy and fewer side effects than other treatments, and it should thus be considered as a firstline therapy in absence epilepsy. PMID:26610892

  3. miR-422a is an independent prognostic factor and functions as a potential tumor suppressor in colorectal cancer

    PubMed Central

    Zheng, Gui-Xi; Qu, Ai-Lin; Yang, Yong-Mei; Zhang, Xin; Zhang, Shou-Cai; Wang, Chuan-Xin

    2016-01-01

    AIM: To determine the expression of miR-422a in colorectal cancer (CRC) tissues and to further explore the prognostic value and function of miR-422a in CRC carcinogenesis. METHODS: miR-422a expression was analyzed in 102 CRC tissues and paired normal mucosa adjacent to carcinoma by quantitative real-time PCR. The relationship of miR-422a expression with clinicopathological parameters was also analyzed. Kaplan-Meier analysis and Cox multivariate analysis were performed to estimate the potential role of miR-422a. Cell proliferation, migration, and invasion were used for in vitro functional analysis of miR-422a. RESULTS: The levels of miR-422a were dramatically reduced in CRC tissues compared with normal mucosa (P < 0.05), and significantly correlated with local invasion (P = 0.004) and lymph node metastasis (P < 0.001). Kaplan-Meier survival and Cox regression multivariate analyses revealed that miR-422a expression (HR = 0.568, P = 0.015) and clinical TNM stage (HR = 2.942, P = 0.003) were independent prognostic factors for overall survival in CRC patients. Furthermore, in vitro experiments showed that overexpression of miR-422a inhibited the proliferation, migration, and invasion of SW480 and HT-29 cells. CONCLUSION: Down-regulation of miR-422a may serve as an independent prognosis factor in CRC. MiR-422a functions as a tumor suppressor and regulates progression of CRC. PMID:27350737

  4. Primary breast lymphoma: Patient profile, outcome and prognostic factors. A multicentre Rare Cancer Network study

    PubMed Central

    Jeanneret-Sozzi, Wendy; Taghian, Alphonse; Epelbaum, Ron; Poortmans, Philip; Zwahlen, Daniel; Amsler, Beat; Villette, Sylviane; Belkacémi, Yazid; Nguyen, Tan; Scalliet, Pierre; Maingon, Philippe; Gutiérrez, Cristina; Gastelblum, Pauline; Krengli, Marco; Raad, Rita Abi; Ozsahin, Mahmut; Mirimanoff, René-Olivier

    2008-01-01

    Background To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL). Methods Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT) with (n = 37) or without (n = 14) chemotherapy. Median RT dose was 40 Gy (range 12–55 Gy). Results Ten (12%) patients progressed locally and 43 (55%) had a systemic relapse. Central nervous system (CNS) was the site of relapse in 12 (14%) cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. Conclusion The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequently. PMID:18380889

  5. Malignant lymphoma of the oral cavity and the maxillofacial region: Overall survival prognostic factors

    PubMed Central

    Morales-Vadillo, Rafael; Sacsaquispe-Contreras, Sonia J.; Barrionuevo-Cornejo, Carlos; Montes-Gil, Jaime; Cava-Vergiú, Carlos E.; Soares, Fernando A.; Chaves-Netto, Henrique D M.; Chaves, Maria G A M.

    2013-01-01

    Objective: To identify the overall survival and prognostic factors of malignant lymphoma of the oral cavity and the maxillofacial region. Study Design: Clinical records data were obtained in order to determine overall survival at 2 and 5 years, the individual survival percentage of each possible prognostic factor with the actuarial technique, and the survival regarding the possible prognostic factors with the actuarial technique and the Log-rank and Cox’s regression tests. Results: Of 151 subjects, an overall survival was 60% at 2 years, and 45% at 5 years. The multivariate analysis demonstrated statistically significant differences for clinical stage (p=0.002), extranodal involvement (p=0.030), presence of human immunodeficiency virus (p=0.032), and presence of Epstein-Barr virus (p=0.010). Conclusion: The advanced clinical stage and the larger number of involved extranodular sites are related to a lower overall survival, as well as, the presence of previous infections such as the human immunodeficiency and the Epstein-Barr virus. Key words:Lymphoma, oral cavity, survival. PMID:23722134

  6. Survival and prognostic factors of motor neuron disease in a multi-ethnic Asian population.

    PubMed

    Goh, Khean-Jin; Tian, Sharen; Shahrizaila, Nortina; Ng, Chiu-Wan; Tan, Chong-Tin

    2011-03-01

    Our objective was to determine the survival and prognostic factors of motor neuron disease (MND) in a multi-ethnic cohort of Malaysian patients. All patients seen at a university medical centre between January 2000 and December 2009 had their case records reviewed for demographic, clinical and follow-up data. Mortality data, if unavailable from records, were obtained by telephone interview of relatives or from the national mortality registry. Of the 73 patients, 64.4% were Chinese, 19.2% Malays and 16.4% Indians. Male: female ratio was 1.43: 1. Mean age at onset was 51.5 + 11.3 years. Onset was spinal in 75.3% and bulbar in 24.7% of the patients; 94.5% were ALS and 5.5% were progressive muscular atrophy (PMA). Overall median survival was 44.9 + 5.8 months. Ethnic Indians had shorter interval from symptom onset to diagnosis and shorter median survival compared to non-Indians. On Cox proportional hazards analysis, poor prognostic factors were bulbar onset, shorter interval from symptom onset to diagnosis and worse functional score at presentation. In conclusion, age of onset and median survival duration are similar to previous reports in Asians. Clinical features and prognostic factors are similar to other populations. In our cohort, ethnic Indians had more rapid disease course accounting for their shorter survival. PMID:21039118

  7. Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer

    PubMed Central

    Elebro, Jacob; Ben Dror, Liv; Heby, Margareta; Nodin, Björn; Jirström, Karin; Eberhard, Jakob

    2016-01-01

    Abstract Background: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. Material and methods: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. Results: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03–4.17) but not in untreated patients (pinteraction = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01–0.73, pinteraction = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10–0.59), regardless of adjuvant treatment. Conclusion: hENT1 expression is a favourable prognostic factor in I-type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio

  8. Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma.

    PubMed

    Nakano, Satoko; Nakamuro, Takako; Yokoyama, Katsuhiko; Kiyosaki, Kunihiro; Kubota, Toshiaki

    2016-01-01

    Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP. PMID:27579175

  9. Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma

    PubMed Central

    Nakamuro, Takako; Yokoyama, Katsuhiko; Kiyosaki, Kunihiro

    2016-01-01

    Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP. PMID:27579175

  10. Prognostic factors in recurrent glioblastoma patients treated with bevacizumab.

    PubMed

    Schaub, Christina; Tichy, Julia; Schäfer, Niklas; Franz, Kea; Mack, Frederic; Mittelbronn, Michel; Kebir, Sied; Thiepold, Anna-Luisa; Waha, Andreas; Filmann, Natalie; Banat, Mohammed; Fimmers, Rolf; Steinbach, Joachim P; Herrlinger, Ulrich; Rieger, Johannes; Glas, Martin; Bähr, Oliver

    2016-08-01

    The value of bevacizumab (BEV) in recurrent glioblastoma is unclear. Imaging parameters and progression-free survival (PFS) are problematic endpoints. Few data exist on clinical factors influencing overall survival (OS) in unselected patients with recurrent glioblastoma exposed to BEV. We retrospectively analyzed 174 patients with recurrent glioblastoma treated with BEV at two German brain tumor centers. We evaluated general patient characteristics, MGMT status, pretreatment, concomitant oncologic treatment and overall survival. Karnofsky performance score, number of prior chemotherapies, number of prior recurrences and combined treatment with irinotecan (IRI) were significantly associated with OS in univariate analysis. We did not find differences in OS related to sex, age, histology, MGMT status, prior surgical treatment or number of prior radiotherapies. Combined treatment with IRI and higher KPS both remained significantly associated with prolonged survival in multivariate analysis, but patients receiving IRI co-treatment had less advanced disease. Grouping into clinically relevant categories revealed an OS of 16.9 months from start of BEV in patients with first recurrence and KPS ≥ 80 % (n = 25). In contrast, in patients with second recurrence and KPS < 80 %, OS was 3.6 months (n = 27). Our observational data support an early use of BEV in patients with good performance status. The benefit of co-treatment with IRI in our cohort seems to be the result of biased patient recruitment. PMID:27193554

  11. [Long-term prognostic factors in Parkinson's disease (author's transl)].

    PubMed

    Guillard, A; Chastang, C

    1978-05-01

    Acturial methods are used to study the correlation between the initial condition and early therapeutic results, and the present condition of 164 parkinsonian patients treated with L. dopa for 4 to 8 years. There is an ineluctable deterioration in motility. There is a lower risk in patients who are autonomous and only slightly akinetic at the beginning of treatment. Intellectual deterioration is seen in some patients only. The risk factors are: males, the clinical forms of Parkinson's disease in which tremor is not predominant, onset of the disease before 60 years of age, and depression and transitory psychotic disorders during the first year of treatment. This deterioration appears 3 to 5 years after starting dopatherapy, which could be the cause. Life expectancy is still reduced by the disease at the present time. It is longer in patients in whom the disease started with isolated tremors, absence of Babinski's sign, and no loss of autonomy, and those in whom a good initial therapeutic result was obtained. PMID:725403

  12. Prognostic factors and biomarkers of congenital obstructive nephropathy.

    PubMed

    Chevalier, Robert L

    2016-09-01

    Congenital obstructive nephropathy (CON) is the leading cause of chronic kidney disease (CKD) in children. Anomalies of the urinary tract are often associated with abnormal nephrogenesis, which is compounded by obstructive injury and by maternal risk factors associated with low birth weight. Currently available fetal and postnatal imaging and analytes of amniotic fluid, urine, or blood lack predictive value. For ureteropelvic junction obstruction, biomarkers are needed for optimal timing of pyeloplasty; for posterior urethral valves, biomarkers of long-term prognosis and CKD are needed. The initial nephron number may be a major determinant of progression of CKD, and most patients with CON who progress to renal failure reach this point in adulthood, presumably compounded by episodes of acute kidney injury. Biomarkers of tubular injury may be of particular value in predicting the need for surgical intervention or in tracking progression of CKD, and must be adjusted for patient age. Discovery of new biomarkers may depend on "unbiased" proteomics, whereby patterns of urinary peptide fragments from patients with CON are analyzed in comparison to controls. Most promising are the analysis of urinary exosomes (restricting biomarkers to relevant tubular cells) and quantitative magnetic resonance imaging techniques allowing precise determination of nephron number and tubular mass. The greatest need is for large prospective multicenter studies with centralized biomarker sample repositories to follow patients with CON from fetal life through adulthood. PMID:26667236

  13. GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer

    PubMed Central

    Lee, Hee Yeon; Jung, Ji-Han; Cho, Hyun-Min; Kim, Sung Hwan; Lee, Kang-Moon; Kim, Hyung-Jin; Lee, Jong Hoon; Shim, Byoung Yong

    2015-01-01

    Purpose We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. Materials and Methods All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m2/day) and leucovorin (20 mg/m2/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Results High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045). Conclusion GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT. PMID:25687871

  14. Expression of store-operated channel components in prostate cancer: the prognostic paradox.

    PubMed

    Perrouin Verbe, Marie-Aimée; Bruyere, Franck; Rozet, Francois; Vandier, Christophe; Fromont, Gaelle

    2016-03-01

    In vitro studies in prostate cancer (PCa) cell lines have suggested a key and complex role of the store-operated channels (SOCs) in major cancer hallmarks, including proliferation, apoptosis, and migration. In the present study, we investigated in vivo the expression of the SOC components transient receptor potential canonical (TRPC) 1, TRPC4, Orai1, and stromal interaction molecule 1 (STIM1), during all stages of PCa progression, and evaluated their prognostic impact in clinically localized cancer (CLC). The expressions of TRPC1, TRPC4, Orai1, STIM1, and the androgen receptor and the proliferation marker Ki-67 were evaluated by immunohistochemistry on tissue microarrays containing samples of normal prostate tissues (n=91), prostatic intraepithelial neoplasia (n=61), CLC surgically treated (n=238), and castration-resistant prostate cancer (CRPC; n=45). All markers significantly increased in CLC compared with normal tissues and (for Orai1 and STIM1) in advanced pT3 tumors compared with pT2. In contrast, their expression decreased in CRPC, particularly for Orai1. In CLC, staining for TRPC1, Orai1 and STIM1 correlated with androgen receptor expression, and TRPC1 status was associated with lower proliferation and longer recurrence-free survival, after adjusting for classical prognostic markers. Although increased SOC expression during PCa progression supports a role in cancer cell migration, the inverse association between TRPC1 and biochemical relapse suggests a protective effect in CLC. Moreover, the dramatic down-regulation of Orai1 in CRPC supports its role in apoptosis at this stage of the disease. These results call for caution when considering SOCs as potential therapeutic targets for PCa. PMID:26826413

  15. Multifocal Glioblastoma Multiforme: Prognostic Factors and Patterns of Progression

    SciTech Connect

    Showalter, Timothy N.; Andrel, Jocelyn; Andrews, David W.; Curran, Walter J.; Daskalakis, Constantine; Werner-Wasik, Maria

    2007-11-01

    Purpose: To assess the progression patterns in patients with multifocal glioblastoma multiforme who had undergone whole brain radiotherapy (WBRT), the historical standard, versus three-dimensional conformal radiotherapy, and to identify predictive treatment and pretreatment factors. Methods and Materials: The records of 50 patients with multifocal glioblastoma multiforme treated with RT were reviewed. Univariate analyses were performed using survival methods and the Cox proportional hazards regression method. Multivariate analyses were performed using the Cox proportional hazards regression method. Results: The mean age was 61 years, and 71% had a Karnofsky performance status (KPS) score of {>=}70. Of the 50 patients, 32% underwent WBRT and 68%, three-dimensional conformal RT. Progression was local in all evaluable patients, as determined by imaging in 38 patients and early neurologic progression in 12. The median time to progression (TTP) was 3.1 months, and the median survival time (MST) was 8.1 months. The significant independent predictors of TTP on multivariate analysis were a KPS score <70 (p = 0.001), the extent of surgery (p = 0.040), a radiation dose <60 Gy (p = 0.027), and the lack of chemotherapy (p = 0.001). The significant independent predictors of a reduced MST were a KPS score <70 (p = 0.022) and the absence of salvage surgery (p = 0.011) and salvage chemotherapy (p = 0.003). Conclusion: Local progression was observed in all patients. On multivariate analysis, no significant difference was found in the TTP or MST between three-dimensional conformal radiotherapy and WBRT. The KPS was a consistent independent predictor of both TTP and MST. On the basis of the progression pattern, we do not recommend WBRT as a mandatory component of the treatment of multifocal glioblastoma multi0011for.

  16. Procalcitonin as a Diagnostic and Prognostic Factor for Tuberculosis Meningitis

    PubMed Central

    Kim, Jinseung; Kim, Si Eun; Park, Bong Soo; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Kim, Sung Eun

    2016-01-01

    Background and Purpose We investigated the potential role of serum procalcitonin in differentiating tuberculosis meningitis from bacterial and viral meningitis, and in predicting the prognosis of tuberculosis meningitis. Methods This was a retrospective study of 26 patients with tuberculosis meningitis. In addition, 70 patients with bacterial meningitis and 49 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed among the three groups. In addition, we analyzed the predictive factors for a prognosis of tuberculosis meningitis using the Glasgow Coma Scale (GCS) at discharge, and the correlation between the level of procalcitonin and the GCS score at discharge. Results Multiple logistic regression analysis showed that a low level of procalcitonin (≤1.27 ng/mL) independently distinguished tuberculosis meningitis from bacterial meningitis. The sensitivity and specificity for distinguishing tuberculosis meningitis from bacterial meningitis were 96.2% and 62.9%, respectively. However, the level of procalcitonin in patients with tuberculosis meningitis did not differ significantly from that in patients with viral meningitis. In patients with tuberculosis meningitis, a high level of procalcitonin (>0.4 ng/mL) was a predictor of a poor prognosis, and the level of procalcitonin was negatively correlated with the GCS score at discharge (r=-0.437, p=0.026). Conclusions We found that serum procalcitonin is a useful marker for differentiating tuberculosis meningitis from bacterial meningitis and is also valuable for predicting the prognosis of tuberculosis meningitis. PMID:27165424

  17. LOX expression in primary nasopharyngeal carcinoma: correlation with prognostic parameters and outcome

    PubMed Central

    Tang, Ling-Quan; Chen, Qiu-Yan; Shao, Jian-Yong; Mai, Hai-Qiang

    2016-01-01

    Lysyl oxidase (LOX) is an extracellular matrix-remodeling enzyme that plays important roles in tumor development and progression. To evaluate the prognostic value of LOX levels in primary nasopharyngeal carcinoma, we performed an immunohistochemical analysis using 233 tissue biopsy specimens from as many patients. We found that the extent of immunohistochemical LOX staining correlated inversely with the clinicopathological features and survival. High LOX expression correlated with decreases in 5-year survival, overall survival, distant metastasis-free survival and disease-free survival (p < 0.05). Cox regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5-year mortality for all patients (hazard ratio [HR], 1.670; 95% confidence interval [95% CI], 1.033–2.701 [p < .005]). Higher LOX expression was also an independent predictor of poor prognosis in patients with nasopharyngeal carcinoma. These findings suggest LOX may be a new biomarker predictive of NPC prognosis and may also be a useful treatment target. PMID:26882568

  18. CD123 immunostaining patterns in systemic mastocytosis: differential expression in disease subgroups and potential prognostic value.

    PubMed

    Pardanani, A; Reichard, K K; Zblewski, D; Abdelrahman, R A; Wassie, E A; Morice Ii, W G; Brooks, C; Grogg, K L; Hanson, C A; Tefferi, A; Chen, D

    2016-04-01

    CD123 is the α-subunit of the interleukin-3 receptor; it represents a potential therapeutic target in systemic mastocytosis (SM) given its absent expression on normal/reactive mast cells (MCs) and aberrant expression on neoplastic MCs. We studied 58 SM patients to define CD123 expression patterns by immunohistochemistry and its clinical significance. Two hematopathologists independently scored bone marrow slides using predefined histologic parameters. In all, 23 patients had indolent SM (ISM), 10 aggressive SM (ASM), 23 SM with associated hematological neoplasm (SM-AHN) and 2 had mast cell leukemia (MCL). MC_CD123 expression was demonstrable in 37 (64%) cases; expression rates were 100%, 61%, 57% and 0% in ASM, ISM, SM-AHN and MCL, respectively (P=0.02). Focal proliferation of plasmacytoid dendritic cells (PDCs) around MC aggregates, suggesting a tumor-promoting role for PDCs, was noted in 44 (76%) cases, and was significantly higher in CD123-positive versus -negative cases (87% versus 50%, P=0.005). CD123 expression and its staining intensity had prognostic value in SM-chronic myelomonocytic leukemia and nonindolent SM patients, respectively. These observations suggest that targeting CD123 in SM may have direct (via MCs) and indirect (via PDCs) antitumor effects and clinical trials to that effect require laboratory correlative studies to address the observed target expression heterogeneity. PMID:26678095

  19. Primary tumor inflammation in gross tumor volume as a prognostic factor for nasopharyngeal carcinoma patients

    PubMed Central

    Peng, Hao; Chen, Lei; Tang, Ling-Long; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Purpose The objective of this study is to investigate the prognostic value of primary tumor inflammation (PTI) in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT). Results PTI was observed in 376/1708 (22.0%) patients, and was present in the sphenoid sinus in 289/376 (76.9%), in the nasal cavity in 27 (7.2%), and in both places in 60 (15.9%). The estimated 4-year local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS) and distant metastasis-free survival (DMFS) rates for PTI vs. non-PTI group were 89.2% vs. 96.1% (P < 0.001), 73.4% vs. 85.1% (P < 0.001), 85.0% vs. 92.1% (P < 0.001) and 83.6% vs. 91.4% (P < 0.001), respectively. After adjustment for these known prognostic factors, PTI was confirmed as an independent prognostic factor for LRFS (HR 2.152, 95% CI 1.318–3.516, P = 0.002), DFS (HR 1.581, 95% CI 1.204–2.077, P = 0.001) and DMFS (HR 1.682, 95% CI 1.177–2.402, P = 0.004). Conclusions Primary tumor inflammation was identified as a strong prognostic factor for patients with NPC in the era of IMRT and should be considered when devising future treatment strategies aimed at improving survival in NPC patients. Materials and Methods Data on 1708 patients with nonmetastatic, histologically-confirmed NPC treated with IMRT between November 2009 and February 2012 at Sun Yat-Sen University Cancer Center were retrospectively reviewed. Patient survival between PTI and non-PTI groups were compared. PMID:26934649

  20. Clinical Outcome and Prognostic Factors of Intensity-Modulated Radiotherapy for T4 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Luo, Yangkun; Gao, Yang; Yang, Guangquan; Lang, Jinyi

    2016-01-01

    Objective. To analyze the clinical outcomes and prognostic factors of intensity-modulated radiotherapy (IMRT) for T4 stage nasopharyngeal carcinoma (NPC). Methods. Between March 2005 and March 2010, 110 patients with T4 stage NPC without distant metastases were treated. All patients received IMRT. Induction and/or concurrent chemotherapy were given. 47 (42.7%) patients received IMRT replanning. Results. The 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 90.1%, 97.0%, 67.5%, 63.9%, and 64.5%, respectively. Eleven patients experienced local-regional failure and total distant metastasis occurred in 34 patients. 45 patients died and 26 patients died of distant metastasis alone. The 5-year LRFS rates were 97.7% and 83.8% for the patients that received and did not receive IMRT replanning, respectively (P = 0.023). Metastasis to the retropharyngeal lymph nodes (RLN) was associated with inferior 5-year OS rate (61.0% versus 91.7%, P = 0.034). The gross tumor volume of the right/left lymph nodes (GTVln) was an independent prognostic factor for DMFS (P = 0.006) and PFS (P = 0.018). GTVln was with marginal significance as the prognostic factor for OS (P = 0.050). Conclusion. IMRT provides excellent local-regional control for T4 stage NPC. Benefit of IMRT replanning may be associated with improvement in local control. Incorporating GTVln into the N staging system may provide better prognostic information. PMID:27195286

  1. Heart rate variability and heart rate recovery as prognostic factors

    PubMed Central

    GRAD, COSMIN

    2015-01-01

    Background and aim Heart rate (HR) can appear static and regular at rest, during exercise or recovery after exercise. However, HR is constantly adjusted due to factors such as breathing, blood pressure control, thermoregulation and the renin-angiotensin system, leading to a more dynamic response that can be quantified using HRV (heart rate variability). HRV is defined as the deviation in time between successive normal heart beat and is a noninvasive method to measure the total variation in a number of HR interval. HRV can serve as measure of autonomic activity of sino-atrial node. The aim of the study was to determine the influence of certain clinical and paraclinical parameters on heart rate recovery after exercise in patients with ischemic heart disease and the relation with HRV using 24 h Holter monitoring. Methods The study included 46 patients who were submitted to cardiovascular exercise stress test and also to 24 h Holter EKG monitoring. Subjects had a mean age of 56.2±11.2 years, with a minimum of 25 and a maximum of 79 years. The study included 22 (47.8%) men and 24 (52.2%) women. Statistical analysis was performed using MedCalc software version 14.8.1. Multivariate analysis consisted of the construction of several multiple linear regression models. A p value of 0.05 was considered statistically significant. Results The HRV values (time domain) were all lower in the IHD compared with the group without coronary heart disease, even if the difference is not statistically significant. Also rest and maximal HR values were similar but during the test varies in the sense that those with IHD had higher values of rest and maximal HR and lower HRR, but not statistically significant. Conclusions HRV is a very easy and safe method if there is an available device and it is used for evaluation of the autonomic nervous system in many cardiovascular diseases, but also in other pathologies. In uncomplicated ischemic heart disease HRV is depressed, but not significant. HRR

  2. Risk factors and prognostic factors of acute kidney injury in children: A retrospective study between 2003 and 2013.

    PubMed

    Zhou, Yan-mei; Yin, Xiao-ling; Huang, Zhi-bin; He, Yong-hua; Qiu, Li-ru; Zhou, Jian-hua

    2015-12-01

    Recent report on epidemiology of acute kidney injury (AKI) is lacking for Chinese children. We aimed to investigate the risk factors for stage and prognostic factors for renal recovery in hospitalized children. Pediatric patients (≤18 years old) admitted during 2003 to 2013 were enrolled in this study. AKI was defined and staged using Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression analysis was performed to determine the risk factors and prognostic factors. The morbidity of pediatric AKI was 0.31% (205/65 237). There were 45 (22.0%) cases in stage III, 30 (14.6%) cases in stage II and 130 (63.4%) cases in stage III. The majority of etiologies were intrinsic renal defects (85.4%). Age, weight, vomit, etiology, blood urea nitrogen (BUN) at admission and several blood gas measurements were associated with AKI stage III. Age (OR=0.894; 95% CI, 0.832-0.962; P=0.003), vomit (OR=2.375; 95% CI, 1.058-5.333; P=0.036) and BUN at admission (OR=1.135; 95% CI, 1.085-1.187; P<0.001) were identified as independent risk factors for AKI stage III. After treatment, 172 (83.9%) patients achieved complete or partial recovery. The mortality was 3.9%. Variables were found as prognostic factors for renal recovery, such as age, stage, hospital stay, BUN at discharge, white blood cells, red blood cells, platelets (PLTs), blood pH and urine blood. Among them, AKI stage (stage III vs. stage I; OR, 6.506; 95% CI, 1.640-25.816; P=0.008), BUN at discharge (OR, 0.918; 95% CI, 0.856-0.984; P=0.016) and PLTs (OR, 1.007; 95% CI, 1.001-1.013; P=0.027) were identified as independent prognostic factors. AKI is still common in Chinese hospitalized children. Identified risk factors and prognostic factors provide guiding information for clinical management of AKI. PMID:26670426

  3. Prognostic significance of Minichromosome maintenance protein 7 and Geminin expression in patients with 109 soft tissue sarcomas

    PubMed Central

    HAMAMOTO, YUKI; SHOMORI, KOHEI; NOSAKA, KANAE; HARUKI, TOMOHIRO; TESHIMA, RYOTA; ITO, HISAO

    2010-01-01

    Minichromosome maintenance complex (MCM2-7) and Geminin are important in the prevention of DNA re-replication in the cell cycle, and are also prognostic markers for numerous human malignancies. The present study examined Minichromosome maintenance protein 7 (MCM7) and Geminin expression in human soft tissue sarcomas (STSs) to clarify their correlation to the clinicopathological factors. Immunohistochemistry was performed to detect the expression of MCM7, Geminin and Ki-67 on paraffin-embedded sections of 109 STSs. Labeling indices (LIs) of the molecules were evaluated in the tumors. Higher LIs of MCM7, Geminin and Ki-67 were significantly correlated with distant metastasis (P<0.01), histological grade (P<0.01) and poor prognosis (P<0.01), respectively. LIs of MCM7 and Geminin were significantly correlated with Ki-67 LIs, (MCM7/Ki-67: rs=0.745, P<0.01 and Geminin/Ki-67: rs=0.604, P<0.01). Multivariate analyses showed that the higher LIs of Geminin, but not MCM7 and Ki-67, were shown to be an independent factor of poorer prognosis (relative risk 2.72, P=0.013). The immunohistochemical expression of MCM7 and Geminin may be novel and useful markers for evaluating the prognosis in patients with human STS. PMID:22966367

  4. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

    PubMed Central

    Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

    2015-01-01

    Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

  5. Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

    PubMed Central

    Martins, Gustavo Rodrigues; Gelaleti, Gabriela Bottaro; Moschetta, Marina Gobbe; Maschio-Signorini, Larissa Bazela; Zuccari, Debora Ap. Pires de Campos

    2016-01-01

    Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-α with procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-α were found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-α protein expression and survival time was observed (p < 0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p < 0.05). In addition, there was a positive correlation between TNF-α and IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer. PMID:26989335

  6. Expression and prognostic relevance of MET and phospho-BAD in non-small cell lung cancer

    PubMed Central

    Sun, Wenze; Ai, Ting; Gao, Ying; Zhang, Yingbing; Cui, Jie; Song, Liping

    2013-01-01

    Background MET is involved in the progression of several types of human cancers, while phospho-BAD(Ser-136) is a key molecule in apoptosis and might be regulated by MET. The aim of this study was to investigate the correlation between altered expression of MET and phospho-BAD in non-small cell lung cancer (NSCLC) and their association with clinicopathologic parameters and overall survival. Methods MET and phospho-BAD(Ser-136) proteins were evaluated by immunohistochemical analysis in 183 paraffin-embedded specimens and were also assessed by Western blotting analysis in 12 frozen tumor tissue samples, which were representative examples of immunohistochemical staining. Results Positive expression of MET and phospho-BAD(Ser-136) occurred in 67.2% and 49.2% of the 183 cases of NSCLC, respectively. However, neither MET expression nor phospho-BAD(Ser-136) expression was associated with any clinicopathologic parameter. A significant correlation was found between MET and phospho-BAD(Ser-136) expression levels evaluated by immunohistochemistry (r = 0.268, P < 0.001). Overexpression of MET was significantly associated with shortened overall survival in univariate analysis (P < 0.001). Moreover, patients with a MET+/phospho-BAD(Ser-136)+ phenotype had a poorer prognosis than others (P < 0.001). Multivariate Cox proportional hazard analysis confirmed that MET expression is a prognostic factor for NSCLC. Conclusion MET expression might be correlated with phospho-BAD(Ser-136) expression, and may be an adverse predictor for NSCLC. Activation of the MET/phospho-BAD(Ser-136) signaling pathway might play a role in the development and progression of NSCLC. PMID:24092988

  7. Osteopontin, E-cadherin, and β-catenin expression as prognostic biomarkers in patients with radically resected gastric cancer.

    PubMed

    Di Bartolomeo, Maria; Pietrantonio, Filippo; Pellegrinelli, Alessandro; Martinetti, Antonia; Mariani, Luigi; Daidone, Maria Grazia; Bajetta, Emilio; Pelosi, Giuseppe; de Braud, Filippo; Floriani, Irene; Miceli, Rosalba

    2016-04-01

    A correlation between osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal β-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer. PMID:25862567

  8. Prognostic factors for 1-week survival in dogs diagnosed with meningoencephalitis of unknown aetiology.

    PubMed

    Cornelis, I; Volk, H A; Van Ham, L; De Decker, S

    2016-08-01

    Although long-term outcomes of meningoencephalitis of unknown aetiology (MUA) in dogs have been evaluated, little is known about short-term survival and initial response to therapy. The aim of this study was to evaluate possible prognostic factors for 7-day survival after diagnosis of MUA in dogs. Medical records were reviewed for dogs diagnosed with MUA between 2006 and 2015. Previously described inclusion criteria were used, as well as 7-day survival data for all dogs. A poor outcome was defined as death within 1 week. Of 116 dogs that met inclusion criteria, 30 (26%) died within 7 days of diagnosis. Assessed variables included age, sex, bodyweight, duration of clinical signs and treatment prior to diagnosis, venous blood glucose and lactate levels, white blood cell count on complete blood count, total nucleated cell count/total protein concentration/white blood cell differentiation on cerebrospinal fluid (CSF) analysis, presence of seizures and cluster seizures, mentation at presentation, neuroanatomical localisation, imaging findings and treatment after diagnosis. Multivariate analysis identified three variables significantly associated with poor outcome; decreased mentation at presentation, presence of seizures, and increased percentage of neutrophils on CSF analysis. Despite initiation of appropriate treatment, more than a quarter of dogs died within 1 week of diagnosis of MUA, emphasising the need for evaluation of short-term prognostic factors. Information from this study could aid clinical staff to provide owners of affected dogs with prognostic information. PMID:27387733

  9. Expression of MAGE-A1, -A9, -A11 in laryngeal squamous cell carcinoma and their prognostic significance: a retrospective clinical study.

    PubMed

    Liu, Shenghui; Sang, Meixiang; Xu, Yuru; Gu, Lina; Liu, Fei; Shan, Baoen

    2016-05-01

    Conclusion The melanoma-associated antigens A1, -A9, -A11 (MAGE-A1, -A9, -A11) are relatively tumor-specific in laryngeal squamous cell carcinoma (LSCC), and could be ideal antigens for LSCC immunotherapy. In addition, MAGE-A9 probably is a poor prognostic marker for LSCC patients. Objective The MAGE-A family belongs to Cancer/testis antigens (CTA). However, the expression pattern of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC is still unclear. This study aims to evaluate the expression and possible prognostic role of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC patients. Methods The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC specimens was investigated by immunohistochemistry, and the association of their expression and the clinical parameters and the survival of LSCC patients were analyzed by chi-square test, Kaplan-Meier survival and Cox regression analysis. Results The expression rates of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC were 54.7%, 46.2%, and 51.9%, respectively. The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC was correlated with clinical stage, lymph node metastasis, and tumor size. The overall survival of LSCC patients with positive MAGE-A1, MAGE-A9, or MAGE-A11 expression was lower than the patients without MAGE-A1, MAGE-A9, or MAGE-A11 expression. Cox's multivariable analysis showed that MAGE-A9 expression was an independently poor prognostic factor for LSCC patients. PMID:26766421

  10. Prognostic significance of CD44V6 expression in osteosarcoma: a meta-analysis.

    PubMed

    Zhang, Yunyuan; Ding, Chunming; Wang, Jing; Sun, Guirong; Cao, Yongxian; Xu, Longqiang; Zhou, Lan; Chen, Xian

    2015-01-01

    Numerous individual studies evaluating the relationship between CD44V6 over-expression and prognostic impact in patients with osteosarcoma (OS) have yielded in conclusive results. This meta-analysis aimed to determine the value of cell adhesion molecule CD44V6 in prognosis of OS by conducting a systematic review and meta-analysis. A comprehensive search was conducted using PubMed (medline), Embase, ISI Web of Knowledge, Springer, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, Wanfang, Weipu, and China National Knowledge Internet (CNKI) databases from inception through May 26, 2015. All available articles written in English or Chinese that investigated the expression of CD44V6 and the prognosis of OS were included. The quantity of the studies was evaluated according to the critical review checklist of the Dutch Cochrane Centre proposed by MOOSE. Finally, a total of eight studies with 486 OS patients were involved and the results indicated that the positive expression of CD44V6 predicts neoplasm metastasis (RR = 1.76, 95 % CI 1.38-2.25, p < 0.00001), and poor survival in OS with the pooled HR of 1.53 (95 % CI 1.25-1.88, p < 0.0001). No significant heterogeneity was observed among all studies. In conclusion, the present meta-analysis and systematic review strongly suggest that CD44V6 over-expression is associated with overall survival rate and metastasis in OS, and may be used as a prognostic biomarker to guide the clinical therapy for OS. PMID:26697855

  11. MicroRNA-711 is a prognostic factor for poor overall survival and has an oncogenic role in breast cancer

    PubMed Central

    HU, JING-YE; YI, WEI; ZHANG, MEI-YIN; XU, RUI; ZENG, LI-SI; LONG, XIAO-RAN; ZHOU, XIAO-MIN; ZHENG, XIAO-FENG STEVEN; KANG, YIBIN; WANG, HUI-YUN

    2016-01-01

    MicroRNAs are important in cancer development and progression. In the present study, the clinical significance and function of microRNA-711 (miR-711) expression in breast cancer were investigated. The expression level of miR-711 was analyzed in breast cancer tissue samples using reverse transcription-quantitative polymerase chain reaction. Cell proliferation, colony formation, apoptosis and Transwell assays were performed in breast cancer cell lines transfected with miR-711 mimics or inhibitors, or control sequence. miR-711 was found to be upregulated in 30 formalin-fixed paraffin-embedded breast cancer tissue samples compared with paired non-cancerous breast tissues (P<0.05). Furthermore, a higher miR-711 expression was demonstrated to be associated with poor overall and disease-free survival times in 161 breast cancer patients, and miR-711 was identified as an independent prognostic factor using multivariate Cox regression analysis. In vitro, overexpression of miR-711 resulted in a significant increase in proliferation, colony formation, migration and invasion of breast cancer cells. By contrast, downregulating miR-711 inhibited cell proliferation, colony formation, migration and invasion and enhanced the rate of apoptosis of breast cancer cells. To the best of our knowledge, the present study is the first to demonstrate that miR-711 is an independent prognostic factor and serves an important oncogenic function in breast cancer, suggesting that miR-711 is a potential biomarker of prognosis and a molecular therapeutic target in breast cancer. PMID:26998141

  12. A profile of prognostic and molecular factors in European and Māori breast cancer patients

    PubMed Central

    2010-01-01

    Background New Zealand Māori have a poorer outcome from breast cancer than non-Māori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Māori and European breast cancer patients from Christchurch, New Zealand. Methods and Results Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Māori, 310 European) were evaluated. Fewer tumours were high grade in Māori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 Māori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1α correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. Conclusions In this Christchurch cohort of breast cancer patients, Māori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences. PMID:20932344

  13. Analysis of prognostic factors affecting mortality in Fournier’s gangrene: A study of 72 cases

    PubMed Central

    Tarchouli, Mohamed; Bounaim, Ahmed; Essarghini, Mohamed; Ratbi, Moulay Brahim; Belhamidi, Mohamed Said; Bensal, Abdelhak; Zemmouri, Adil; Ali, Abdelmounaim Ait; Sair, Khalid

    2015-01-01

    Introduction: Fournier’s gangrene is a rapidly progressing necrotizing fasciitis of the perineum and genital area associated with a high mortality rate. We presented our experience in managing this entity and identified prognostic factors affecting mortality. Methods: We carried out a retrospective study of 72 patients treated for Fournier’s gangrene at our institution between January 2005 and December 2014. Patients were divided into survivors and non-survivors and potential prognostic factors were analyzed. Results: Of the 72 patients, 64 were males (89%) and 8 females (11%), with a mean age of 51 years. The most common predisposing factor was diabetes mellitus (38%). The mortality rate was 17% (12 patients died). Statistically significant differences were not found in age, gender, and predisposing factors, except in heart disease (p = 0.038). Individual laboratory parameters significantly correlating with mortality included hemoglobin (p = 0.023), hematocrit (p = 0.019), serum urea (p = 0.009), creatinine (p = 0.042), and potassium (p = 0.026). Severe sepsis on admission and the extent of affected surface area also predicted higher mortality. Others factors, such as duration of symptoms before admission, number of surgical debridement, diverting colostomy and length of hospital stay, did not show significant differences. The median Fournier’s Gangrene Severity Index (FGSI) was significantly higher in non-survivors (p = 0.002). Conclusion: Fournier’s gangrene is a severe surgical emergency requiring early diagnosis and aggressive therapy. Identification of prognostic factors is essential to establish an optimal treatment and to improve outcome. The FGSI is a simple and valid method for predicting disease severity and patient survival. PMID:26600888

  14. Novel prognostic genes of diffuse large B-cell lymphoma revealed by survival analysis of gene expression data

    PubMed Central

    Li, Chenglong; Zhu, Biao; Chen, Jiao; Huang, Xiaobing

    2015-01-01

    Objective This study aimed to identify prognostic genes for diffuse large B-cell lymphoma (DLBCL), using bioinformatic methods. Methods Five gene expression data sets were downloaded from the Gene Expression Omnibus database. Significance analysis of microarrays algorithm was used to identify differentially expressed genes (DEGs) from two data sets. Functional enrichment analysis was performed for the DEGs with the Database for Annotation, Visualization and Integration Discovery (DAVID). Survival analysis was performed with the Kaplan–Meier method using function survfit from package survival of R for the other three data sets. Cox univariate regression analysis was used to further screen out prognostic genes. Results Thirty-one common DEGs were identified in the two data sets, mainly enriched in the regulation of lymphocyte activation, immune response, and interleukin-mediated signaling pathway. Combined with 47 DLBCL-related genes acquired by literature retrieval, a total of 78 potential prognostic genes were obtained. Cases from the other three data sets were used in hierarchical clustering, and the 78 genes could cluster them into several subtypes with significant differences in survival curves. Cox univariate regression analysis revealed 45, 33, and eleven prognostic genes in the three data sets, respectively. Five common prognostic genes were revealed, including LCP2, TNFRSF9, FUT8, IRF4, and TLE1, among which LCP2, FUT8, and TLE1 were novel prognostic genes. Conclusion Five prognostic genes of DLBCL were identified in this study. They could not only be used for molecular subtyping of DLBCL but also be potential targets for treatment. PMID:26604798

  15. Preoperative Neutrophil-to-Lymphocyte Ratio as a Predictive and Prognostic Factor for High-Grade Serous Ovarian Cancer

    PubMed Central

    Bi, Rui; Ju, Xingzhu; Chen, Xiaojun; Yang, Wentao; Wu, Xiaohua

    2016-01-01

    Objective We aimed to demonstrate the clinical and prognostic significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in high-grade serous ovarian cancer (HGSC). Methods We retrospectively investigated 875 patients who underwent primary staging or debulking surgery for HGSC between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which were expressed as hazard ratios (HRs). Results The NLRs ranged from 0.30 to 24.0. The median value was 3.24 and used as the cutoff value to discriminate between the high-NLR (≥3.24) and low-NLR (<3.24) groups. A high preoperative NLR level was associated with an advanced FIGO stage, increased CA125 level, more extensive ascites, worse cytoreduction outcome and chemoresistance. For univariate analyses, a high NLR was associated with reduced PFS (p<0.001) and OS (p<0.001). In multivariate analyses, a high NLR was still an independent predictor of PFS (p = 0.011), but not OS (p = 0.148). Conclusion Our study demonstrated that NLR could reflect tumor burden and clinical outcomes to a certain extent and should be regarded as a predictive and prognostic parameter for HGSC. PMID:27203425

  16. A systematic review of early prognostic factors for persistent pain following acute orthopedic trauma

    PubMed Central

    Clay, Fiona J; Watson, Wendy L; Newstead, Stuart V; McClure, Roderick J

    2012-01-01

    BACKGROUND: Acute orthopedic trauma contributes substantially to the global burden of disease. OBJECTIVES: The present systematic review aimed to summarize the current knowledge concerning prognostic factors for the presence of persistent pain, pain severity and pain-related disability following acute orthopedic trauma involving a spectrum of pathologies to working-age adults. METHODS: The Ovid MEDLINE and EMBASE databases were searched for level II prognostic studies published between January 1996 and October 2010. Studies that were longitudinal and reported results with multivariate analyses appropriate for prognostic studies were included. Studies that addressed two specific injury types that have been the subject of previous reviews, namely, injuries to the spinal column and amputations, were excluded. RESULTS: The searches yielded 992 studies; 10 studies met the inclusion criteria and were rated for methodological quality. Seventeen factors were considered in more than one cohort. There was strong evidence supporting the association of female sex, older age, high pain intensity, preinjury anxiety or depression, and fewer years of education with persistent pain outcomes. There was moderate evidence supporting the association between postinjury depression or anxiety with persistent pain, and that injury severity was not a risk factor for ongoing pain. CONCLUSION: Many individuals experience persistent pain following acute trauma. Due to the lack of studies, the use of different constructs to measure the same factor and the methodological limitations associated with many of the studies, the present review was only able to reliably identify a limited set of factors that predicted persistent pain. Recommendations for the conduct of future methodologically rigorous studies of persistent pain are provided. PMID:22518366

  17. Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse.

    PubMed

    Zhang, Na; Ouyang, Taohui; Kang, Huicong; Long, Wang; Thomas, Benjamin; Zhu, Suiqiang

    2015-09-01

    To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P < 0.05). High-risk category was associated with just lower PFS, but not OS. In multivariate analysis, complete resection and desmoplastic pathology were independently predictive factors of improved PFS and OS. In adult medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes. PMID:26026861

  18. The Prognostic Role of STEAP1 Expression Determined via Immunohistochemistry Staining in Predicting Prognosis of Primary Colorectal Cancer: A Survival Analysis

    PubMed Central

    Lee, Ching-Hsiao; Chen, Sung-Lang; Sung, Wen-Wei; Lai, Hung-Wen; Hsieh, Ming-Ju; Yen, Hsu-Heng; Su, Tzu-Cheng; Chiou, Yu-Hu; Chen, Chia-Yu; Lin, Cheng-Yu; Chen, Mei-Ling; Chen, Chih-Jung

    2016-01-01

    STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients. The mean and medium follow-up times after surgery were 5.1 and 3.9 years, respectively. A total of 139 patients died during the 13 years of follow-up in the survey period. The prognostic value of STEAP1 with respect to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. In total, 164 samples displayed detectable STEAP1 expression in the cytoplasm and membrane. Low STEAP1 expression was correlated with poor overall survival (five-year survival: 33.7% vs. 57.0%, low expression vs. high expression, p = 0.020). Accordingly, multivariate analysis identified low STEAP1 expression as an independent risk factor (hazard ratio = 1.500, p = 0.018), especially in elderly patients or those with late stage cancers, late T values, and early N values. We suggest that analysis of STEAP1 expression by immunohistochemical staining could serve as an independent prognostic marker for colorectal patients. This finding should be validated by other investigative groups. PMID:27104516

  19. Expression and Prognostic Significance of p53 in Glioma Patients: A Meta-analysis.

    PubMed

    Jin, Yueling; Xiao, Weizhong; Song, Tingting; Feng, Guangjia; Dai, Zhensheng

    2016-07-01

    Glioma is a brain tumor deriving from the neoplastic glial cells or neuroglia. Due to its resistance to anticancer drugs and different disease progress of individuals, patients with high-grade glioma are difficult to completely cure, leading to a poor prognosis and low overall survival. Therefore, there is an urgent need to look for prognostic and diagnostic indicators that can predict glioma grades. P53 is one of the widely studied biomarkers in human glioma. The purpose of this study was to comprehensively evaluate the significance of p53 expression in glioma grades and overall survival. We searched commonly used electronic databases to retrieve related articles of p53 expression in glioma. Overall, a total of 21 studies including 1322 glioma patients were finally screened out. We observed that the frequency of p53 immuno-positivity was higher in high-grade patients than that in low-grade category (63.8 vs. 41.6 %), and our statistic analysis indicated that p53 expression was associated with pathological grade of glioma (OR 2.93, 95 % CI 1.87-4.60, P < 0.00001). This significant correction was also found in 1-, 3- and 5-year overall survival. However, no positive relationship was found between age, sex, tumor size and p53 expression in patients with glioma. In conclusion, our results suggested that p53 immunohistochemical expression might have an effective usefulness in predicting the prognosis in patients with glioma. PMID:27038932

  20. Prognostic value of melanoma cell adhesion molecule expression in cancers: a meta-analysis

    PubMed Central

    Zhu, Guoqing; Zhang, Xiao; Wang, Yulan; Xiong, Huizi; Zhao, Yinghui; Wang, Jiayi; Sun, Fenyong

    2015-01-01

    Melanoma cell adhesion molecule (MACM) has been reported in many studies as a novel bio-marker for its prognosis value in cancers. But the prognosis significance of MACM expression in cancer remains inconclusive. Therefore, we conducted a system review and meta-analysis to assess its prognosis value in cancers. A systematic search through Pubmed, EMBASE and Cochran Library database was conducted. Hazard Ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the prognosis value of MACM expression. Eleven studies with 2657 cases were included after sorting out 462 articles for this meta-analysis. The results of the fixed-model depending on the heterogeneity in studies demonstrated that MACM expression was significantly associated with overall survival (OS) in cancer (HR=2.84, 95% CI: 1.10-7.31, P<0.00001). Furthermore, subgroup analysis indicated that high expressed MACM predicted a poor OS in both Asian (HR=2.52, 95% CI: 1.80-3.52, P<0.00001) and Caucasian (HR=2.40, 95% CI: 2.01-2.88, P<0.00001). In conclusion, high expression of MACM was significantly associated with a poor prognostic outcome in cancer. MACM can be regarded as a novel bio-marker in different types of cancers and can be used to evaluate the prognosis of therapeutic effect during clinical practices. PMID:26550117

  1. Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

    PubMed

    Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

    2015-07-30

    A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). PMID:25924725

  2. Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer

    PubMed Central

    Lu, Wei; Cao, Yang; Zhang, Yijian; Li, Sheng; Gao, Jian; Wang, Xu-An; Mu, Jiasheng; Hu, Yun-Ping; Jiang, Lin; Dong, Ping; Gong, Wei; Liu, Yingbin

    2016-01-01

    Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression. PMID:27283076

  3. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group

    PubMed Central

    Hilden, Joanne M.; Dinndorf, Patricia A.; Meerbaum, Sharon O.; Sather, Harland; Villaluna, Doojduen; Heerema, Nyla A.; McGlennen, Ron; Smith, Franklin O.; Woods, William G.; Salzer, Wanda L.; Johnstone, Helen S.; Dreyer, Zoann; Reaman, Gregory H.

    2006-01-01

    Infant acute lymphoblastic leukemia (ALL) has a poor therapeutic outcome despite attempts to treat it based on prognostic factor–guided therapy. This is the first cooperative group trial characterizing all infants at the molecular level for MLL/11q23 rearrangement. All infants enrolled on Children's Cancer Group (CCG) 1953 were tested for MLL rearrangement by Southern blot and the 11q23 translocation partner was identified (4;11, 9;11, 11;19, or “other”) by reverse-transcriptase polymerase chain reaction (PCR). One hundred fifteen infants were enrolled; overall event-free survival (EFS) was 41.7% (SD = 9.2%) and overall survival (OS) was 44.8% at 5 years. Five-year EFS for MLL-rearranged cases was 33.6% and for MLL-nonrearranged cases was 60.3%. The difference in EFS between the 3 major MLL rearrangements did not reach statistical significance. Multivariate Cox regression analyses showed a rank order of significance for negative impact on prognosis of CD10 negativity, age younger than 6 months, and MLL rearrangement, in that order. Toxicity was the most frequent cause of death. Relapse as a first event in CCG 1953 was later (median, 295 days) compared with CCG 1883 historic control (median, 207 days). MLL/11q23 rearrangement, CD10 expression, and age are important prognostic factors in infant ALL, but molecular 11q23 translocation partners do not predict outcome. PMID:16556894

  4. Assessment of microtubule-associated protein (MAP)-Tau expression as a predictive and prognostic marker in TACT; a trial assessing substitution of sequential docetaxel for FEC as adjuvant chemotherapy for early breast cancer.

    PubMed

    Irshad, S; Gillett, C; Pinder, S E; A'hern, R P; Dowsett, M; Ellis, I O; Bartlett, J M S; Bliss, J M; Hanby, A; Johnston, S; Barrett-Lee, P; Ellis, P; Tutt, A

    2014-04-01

    The TACT trial is the largest study assessing the benefit of taxanes as part of adjuvant therapy for early breast cancer. The goal of this translational study was to clarify the predictive and prognostic value of Tau within the TACT trial. Tissue microarrays (TMA) were available from 3,610 patients. ER, PR, HER2 from the TACT trial and Tau protein expression was determined by immunohistochemistry on duplicate TMAs. Two parallel scoring systems were generated for Tau expression ('dichotomised' vs. 'combined' score). The positivity rate of Tau expression was 50 % in the trial population (n = 2,483). Tau expression correlated positively with ER (p < 0.001) and PR status (p < 0.001); but negatively with histological grade (p < 0.001) and HER2 status (p < 0.001). Analyses with either scoring systems for Tau expression demonstrated no significant interaction between Tau expression and efficacy of docetaxel. Contrary to the hypothesis that taxane benefit would be enriched in Tau negative/low patients, the only groups with a suggestion of a reduced event rate in the taxane group were the HER2-positive, Tau positive subgroups. Tau expression was seen to be a prognostic factor on univariate analysis associated with an improved DFS, independent of the treatment group (p < 0.001). It had no prognostic value in ER-negative tumours and the weak prognostic effect of Tau in ER-positive tumours (p = 0.02) diminished, when considering ER as an ordinal variable. On multivariable analyses, Tau had no prognostic value in either group. In addition, no significant interaction between Tau expression and benefit from docetaxel in patients within the PR-positive and negative subsets was seen. This is now the second large adjuvant study, and the first with quantitative analysis of ER and Tau expression, failing to show an association between Tau and taxane benefit with limited utility as a prognostic marker for Tau in ER-positive early breast cancer patients. PMID:24519386

  5. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Aust, Stefanie; Knogler, Thomas; Pils, Dietmar; Obermayr, Eva; Reinthaller, Alexander; Zahn, Lisa; Radlgruber, Ilja; Mayerhoefer, Marius Erik; Grimm, Christoph; Polterauer, Stephan

    2015-01-01

    Objective Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients. Methods We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient’s outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis. Results Muscle attenuation (MA)—a well established BCM parameter—is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA—reflecting a state of cachexia—is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively). Conclusion MA—ascertained by routine pre-operative CT—is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA. PMID:26457674

  6. Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma

    PubMed Central

    Ito, Takamichi; Kohashi, Kenichi; Yamada, Yuichi; Iwasaki, Takeshi; Maekawa, Akira; Kuda, Masaaki; Hoshina, Daichi; Abe, Riichiro; Furue, Masutaka; Oda, Yoshinao

    2016-01-01

    Background: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. Methods: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Results: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. Conclusions: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma. PMID:27162541

  7. Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma

    PubMed Central

    Ni, Jia-Yan; Sun, Hong-Liang; Chen, Yao-Ting; Luo, Jiang-Hong; Chen, Dong; Jiang, Xiong-Ying; Xu, Lin-Feng

    2014-01-01

    AIM: To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC). METHODS: Clinical data of 86 patients who underwent TACE combined with MWA between January 2006 and December 2013 were retrospectively analyzed in this study. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 47.6 mo, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ2 = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ2 = 29.765, P = 0.000), Child-Pugh class (χ2 = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ2 = 43.086, P = 0.000), arterio-venous fistula (χ2 = 29.791, P = 0.000), MWA therapy times (χ2 = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ2 = 28.660, P = 0.000) and targeted drug usage (χ2 = 10.901, P = 0.001) were found to be significantly associated with overall survival by univariate analysis. Multivariate analysis identified that tumor size (95%CI: 1.608-4.962, P = 0.000), BCLC stage (95%CI: 1.016-2.208, P = 0.020), PVTT (95%CI: 2.062-9.068, P = 0.000), MWA therapy times (95%CI: 0.402-0.745, P = 0.000), ECOG score (95%CI: 1.012-3.053, P = 0.045) and targeted drug usage (95%CI: 1.335-3.143, P = 0.001) were independent prognostic factors associated with overall survival. CONCLUSION: Superior performance status, MWA treatment and targeted drug were favorable factors, and large HCC, PVTT and advanced BCLC

  8. Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma.

    PubMed

    Koirala, Pratistha; Roth, Michael E; Gill, Jonathan; Piperdi, Sajida; Chinai, Jordan M; Geller, David S; Hoang, Bang H; Park, Amy; Fremed, Michael A; Zang, Xingxing; Gorlick, Richard

    2016-01-01

    Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival. PMID:27456063

  9. Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma

    PubMed Central

    Koirala, Pratistha; Roth, Michael E.; Gill, Jonathan; Piperdi, Sajida; Chinai, Jordan M.; Geller, David S.; Hoang, Bang H.; Park, Amy; Fremed, Michael A.; Zang, Xingxing; Gorlick, Richard

    2016-01-01

    Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival. PMID:27456063

  10. Prognostic factors for the progression of Parkinson's disease: a systematic review.

    PubMed

    Post, Bart; Merkus, Maruschka P; de Haan, Rob J; Speelman, Johannes D

    2007-10-15

    The purpose of this systematic review is to summarize studies that describe the course of Parkinson's disease (PD) and to identify factors that predict change in motor impairment, disability, and quality of life. A literature search was conducted in MEDLINE, EMBASE, CINAHL, and Web of Science limited to the English, French, German, Spanish, and Dutch language. Reports were selected if the study involved subjects with PD, the outcome measures described impairment, disability, or quality of life and follow-up was at least 6 months. All included studies were scored for methodological quality. Data were extracted and summarized in a best evidence synthesis. We screened 1,535 titles and abstracts, of which 27 fulfilled our inclusion criteria. A meta-analysis to quantitatively aggregate progression scores of motor impairment and disability was not possible because of the wide variety of outcome measures used and the heterogeneous study populations. Limited evidence is found for lower UPDRS-ME at baseline, dementia and SE < 70% as prognostic factors for future motor impairment. There is strong evidence for higher age at onset and higher PIGD-score; and limited evidence for higher bradykinesia-score, non-tremor dominant subtype, symmetrical disease at baseline, and depression as prognostic factors for progression of disability. Prognostic factors were identified for impairment and disability. The literature on prognosis in PD is not fulfilling the high methodological standards applied nowadays. There is a need for prospective cohorts of PD patients assembled at a common early point in the disease with long time follow-up. PMID:17595026

  11. Prognostic factors for salvage endoscopic resection for esophageal squamous cell carcinoma after chemoradiotherapy or radiotherapy alone

    PubMed Central

    Kondo, Shinya; Tajika, Masahiro; Tanaka, Tsutomu; Kodaira, Takeshi; Mizuno, Nobumasa; Hara, Kazuo; Hijioka, Susumu; Imaoka, Hiroshi; Goto, Hidemi; Yamao, Kenji; Niwa, Yasumasa

    2016-01-01

    Background and study aims: Endoscopic resection is one treatment option for residual or locally recurrent esophageal cancer after definitive chemoradiotherapy or radiotherapy alone. However, little is known about the clinical benefit of salvage endoscopic resection for these lesions. Therefore, the effectiveness and prognostic factors of salvage endoscopic resection were investigated. Patients and methods: A total of 37 patients with esophageal squamous cell carcinoma (SCC) who underwent salvage endoscopic resection after definitive chemoradiotherapy or radiotherapy alone were reviewed. The method of salvage endoscopic resection was endoscopic mucosal resection using a cap (EMR-C), strip biopsy, or endoscopic submucosal dissection. The effectiveness and prognostic factors of salvage endoscopic resection were retrospectively analyzed. Results: A total of 37 patients with 49 lesions underwent salvage endoscopic resection. Baseline clinical stages were I in 23 patients, II in 3 patients, III in 9 patients, and IV in 2 patients. The number of locoregional recurrences and residual lesions were 35 and 14, respectively. The curative en bloc resection rate was 53.1 % (26/49). The total incidence of complications was 18.9 % (7/37); all were successfully managed conservatively. The 3-year and 5-year overall survival rates were 72.9 % and 53.3 %, respectively, with a median follow-up period of 54 months. Baseline clinical T1 – 2 and N0 were significant factors for good prognosis in terms of overall survival on univariate analysis. Conclusions: Salvage endoscopic resection, especially EMR-C, is a safe and feasible procedure to control residual or recurrent superficial esophageal SCC after definitive chemoradiotherapy or radiotherapy alone. The present results showed that baseline clinical T1 – 2 and N0 before chemoradiotherapy or radiotherapy were significant prognostic factors. PMID:27540571

  12. Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia.

    PubMed

    Staffas, Anna; Kanduri, Meena; Hovland, Randi; Rosenquist, Richard; Ommen, Hans Beier; Abrahamsson, Jonas; Forestier, Erik; Jahnukainen, Kirsi; Jónsson, Ólafur G; Zeller, Bernward; Palle, Josefine; Lönnerholm, Gudmar; Hasle, Henrik; Palmqvist, Lars; Ehrencrona, Hans

    2011-11-24

    Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information. PMID:21967978

  13. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications

    PubMed Central

    Janik, S.; Schiefer, A. I.; Bekos, C.; Hacker, P.; Haider, T.; Moser, J.; Klepetko, W.; Müllauer, L.; Ankersmit, H. J.; Moser, B.

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated. PMID:27097982

  14. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.

    PubMed

    Janik, S; Schiefer, A I; Bekos, C; Hacker, P; Haider, T; Moser, J; Klepetko, W; Müllauer, L; Ankersmit, H J; Moser, B

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated. PMID:27097982

  15. AB179. KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma

    PubMed Central

    Guo, Zhongqiang; Liu, Jin; Su, Boxing; Li, Xuesong; Zhou, Liqun

    2014-01-01

    Objective Potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), plays an essential role in potassium balance by transporting potassium out of cells. KCNJ1 variation is associated with multiple diseases, such as antenatal Bartter syndrome and diabetes. However, the role of KCNJ1 in clear cell renal cell carcinoma (ccRCC) is still unknown. The aim of this study was to detect the expression of KCNJ1 in ccRCC and determine the relationship of KCNJ1 expression with the progression and prognosis of ccRCC. Methods Expression of KCNJ1 was evaluated in ccRCC tissues and cell lines by qRT-PCR, Western blot and immunohistochemistry analysis. The relationship between KCNJ1 expression and clinicopathological characteristics was analyzed. P3xFLAG-CMV-14 vector containing KCNJ1 was constructed, and used for infecting ccRCC cell lines 786-O and Caki-2. The effects of KCNJ1 on cell proliferation, invasion and apoptosis were detected in ccRCC cell lines using cell proliferation assay, transwell assay and flow cytometry. Results KCNJ1 was low-expressed in ccRCC tissues samples and cell lines. The KCNJ1 expression level was significantly associated with tumor pathology grade (P=0.002), and clinical stage (P=0.023). Furthermore, the KCNJ1 expression was a prognostic factor of ccRCC patient’s survival (P=0.033). The re-expression of KCNJ1 in 786-O and Caki-2 significantly inhibited cancer cell growth and invasion, and promoted cancer cell apoptosis. Conclusions Taken together, we concluded that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis.

  16. Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis

    PubMed Central

    Hu, Mingming; Hu, Ying; He, Jiabei; Li, Baolan

    2016-01-01

    Background Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis. Method Studies were identified by an electronic search of PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang databases, including publications prior toAugust 2014. Pooled hazard ratios (HR) for overall survival (OS) were aggregated and quantitatively analyzed by meta-analysis. Results Twenty-two studies (n = 2154) were evaluated in the meta-analysis. Combined HR suggested that bFGF overexpression had an adverse impact on survival of patients with lung cancer(HR = 1.202,95%CI, 1.022–1.382). Our subgroup analysis revealed that the combined HR evaluating bFGF expression on OS in operable non-small cell lung cancer (NSCLC) was 1.553 (95%CI, 1.120–1.986); the combined HR in small cell lung cancer (SCLC) was 1.667 (95%CI, 1.035–2.299). There was no significant impact of bFGF expression on survival in advanced NSCLC. Conclusion This meta-analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC, but is not associated with outcome in advanced NSCLC. The data suggests that high bFGF expression is highly related to poor prognosis. Nevertheless,more high-quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer. PMID:26824699

  17. Distinct prognostic values of four-Notch-receptor mRNA expression in ovarian cancer.

    PubMed

    Zhou, Xinling; Teng, Lingling; Wang, Min

    2016-05-01

    Notch signaling pathway includes ligands and Notch receptors, which are frequently deregulated in several human malignancies including ovarian cancer. Aberrant activation of Notch signaling has been linked to ovarian carcinogenesis and progression. In the current study, we used the "Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information from a total of 1306 ovarian cancer patients were used to access the prognostic value of four Notch receptors in ovarian cancer patients. Hazard ratio (HR), 95 % confidence intervals, and log-rank P were calculated. Notch1 messenger RNA (mRNA) high expression was not found to be correlated to overall survival (OS) for all ovarian cancer, as well as in serous and endometrioid cancer patients followed for 20 years. However, Notch1 mRNA high expression is significantly associated with worsen OS in TP53 wild-type ovarian cancer patients, while it is significantly associated with better OS in TP53 mutation-type ovarian cancer patients. Notch2 mRNA high expression was found to be significantly correlated to worsen OS for all ovarian cancer patients, as well as in grade II ovarian cancer patients. Notch3 mRNA high expression was found to be significantly correlated to better OS for all ovarian cancer patients, but not in serous cancer patients and endometrioid cancer patients. Notch4 mRNA high expression was not found to be significantly correlated to OS for all ovarian cancer patients, serous cancer patients, and endometrioid cancer patients. These results indicate that there are distinct prognostic values of four Notch receptors in ovarian cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of ovarian cancer and for developing tools to more accurately predict their prognosis. Based on our results, Notch1 could be a potential drug target of TP53 wild-type ovarian cancer and Notch2 could be a potential drug

  18. Prognostic and Clinicopathological Significance of Downregulated E-Cadherin Expression in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

    PubMed Central

    Xian, Lei

    2014-01-01

    Background Many studies have investigated the prognostic role of E-cadherin in patients with NSCLC; however, the result still remains inconclusive. An up-to data system review and meta-analysis was necessary to give a comprehensive evaluation of prognostic role of E-cadherin in NSCLC. Methods Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between E-cadherin expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with NSCLC. Subgroup analysis according to race, percentage of reduced/negative E-cadherin expression, histological type, and sample size were also conducted. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association. Results A total of 29 studies including 4010 patients were qualified for analysis. The analysis suggested that downregulated E-cadherin expression was significant associated with unfavorable overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS) in patients with NSCLC. Subgroup analysis by race, percentage of reduced/negative E-cadherin expression, sample size also found the significant association in OS. When only the stage I NSCLC were considered, downregulated E-cadherin expression still had an unfavorable impact on OS. Additionally, downregulated E-cadherin expression was significantly associated with differentiation grade, lymphnode metastasis, vascular invasion, and TNM stage. Conclusion Downregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC. PMID:24978478

  19. The prognostic significance of specific HOX gene expression patterns in ovarian cancer.

    PubMed

    Kelly, Zoe; Moller-Levet, Carla; McGrath, Sophie; Butler-Manuel, Simon; Kavitha Madhuri, Thumuluru; Kierzek, Andrzej M; Pandha, Hardev; Morgan, Richard; Michael, Agnieszka

    2016-10-01

    HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials. PMID:27225067

  20. The expression and prognostic relevance of indoleamine 2,3-dioxygenase in tongue squamous cell carcinoma.

    PubMed

    Seppälä, Miia; Halme, Elina; Tiilikainen, Lauri; Luukkainen, Annika; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-07-01

    Conclusion IDO might be useful for predicting progression of primary tumor stage T2 and T3 in tongue squamous cell carcinoma (TSCC), but does not seem like a specific biomarker for diagnosing TSCC and predicting patient survival. Objectives Indoleamine 2,3-dioxygenase (IDO) is expressed in many cells and it catabolises the essential amino acid tryptophan to kynurenine. IDO acts as an immune modulator through suppression of T-cell immunity and other pathways. In cancer cells, IDO has been proposed to promote tumor progression by enabling malignant cells to escape from the immune system. The aim of this study was to evaluate the association and prognostic relevance of IDO expression in TSCC. Method One hundred and eight retrospective tongue and lymph node specimens were stained immunohistochemically with monoclonal antibody anti-indoleamine 2,3-dioxygenase. The relative abundance of IDO positive epithelial cells, IDO staining intensity, and inflammation were assessed semi-quantitatively with light microscopy. Results IDO was expressed stronger in tongue hyperplasia than in TSCC. However, IDO expression associated with poor survival in the sub-groups with primary tumor stage T2-T4 and in the sub-group with strong inflammation in tumors' invasive front. PMID:26982018

  1. The prognostic potential and oncogenic effects of PRR11 expression in hilar cholangiocarcinoma

    PubMed Central

    Qian, Baohua; Yu, Wenlong; Li, Wenfeng; Yu, Guanzhen; Gao, Yong

    2015-01-01

    PRR11 is a newly identified oncogene in lung cancer, yet its role in others tumors remains unclear. Gastrointestinal tissue microarrays were used to evaluate PRR11 expression and its association with clinical outcome was analyzed in patients with hilar cholangiocarcinoma. Overexpression of PRR11 was observed in esophageal, gastric, pancreatic, colorectal, and hilar cholangiocarcinoma. Expression of PRR11 correlated with lymph node metastasis and CA199 level in two HC patient cohorts. After an R0 resection, a high level of PRR11 expression was found to be an independent indicator of recurrence (P = 0.001). In cell culture, PRR11 silencing resulted in decreased cellular proliferation, cell migration, tumor growth of QBC939 cells. Microarray analysis revealed that several genes involved in cell proliferation, cell adhesion, and cell migration were altered in PRR11-knockout cells, including: vimentin (VIM), Ubiquitin carboxyl-terminal hydrolase 1 (UCHL1), early growth response protein (EGR1), and System A amino acid transporter1 (SNAT1). Silencing PRR11 inhibited the expression of UCHL1, EGR1, and SNAT1 proteins, with immunoassays revealing a significant correlation among the levels of these four proteins. These results indicate that PRR11 is an independent prognostic indicator for patients with HC. PMID:25971332

  2. Prognostic prediction through biclustering-based classification of clinical gene expression time series.

    PubMed

    Carreiro, André V; Anunciação, Orlando; Carriço, João A; Madeira, Sara C

    2011-01-01

    The constant drive towards a more personalized medicine led to an increasing interest in temporal gene expression analyzes. It is now broadly accepted that considering a temporal perpective represents a great advantage to better understand disease progression and treatment results at a molecular level. In this context, biclustering algorithms emerged as an important tool to discover local expression patterns in biomedical applications, and CCC-Biclustering arose as an efficient algorithm relying on the temporal nature of data to identify all maximal temporal patterns in gene expression time series. In this work, CCC-Biclustering was integrated in new biclustering-based classifiers for prognostic prediction. As case study we analyzed multiple gene expression time series in order to classify the response of Multiple Sclerosis patients to the standard treatment with Interferon-β, to which nearly half of the patients reveal a negative response. In this scenario, using an effective predictive model of a patient's response would avoid useless and possibly harmful therapies for the non-responder group. The results revealed interesting potentialities to be further explored in classification problems involving other (clinical) time series. PMID:21926438

  3. Expression, prognostic significance and mutational analysis of protein tyrosine phosphatase SHP-1 in chronic myeloid leukemia.

    PubMed

    Papadopoulou, Vasiliki; Kontandreopoulou, Elina; Panayiotidis, Panayiotis; Roumelioti, Maria; Angelopoulou, Maria; Kyriazopoulou, Lydia; Diamantopoulos, Panagiotis T; Vaiopoulos, George; Variami, Eleni; Kotsianidis, Ioannis; Athina Viniou, Nora

    2016-05-01

    The protein tyrosine phosphatase SHP-1 dephosphorylates BCR-ABL1, thereby serving as a potential control mechanism of BCR-ABL1 kinase activity. Pathways regulating SHP-1 expression, which could be exploited in the therapeutics of TKI-resistant chronic myeloid leukemia (CML), remain unknown. Moreover, the questions of whether there is any kind of SHP-1 deregulation in CML, contributing to disease initiation or evolution, as well as the question of prognostic significance of SHP-1, have not been definitively answered. This study shows moderately lower SHP-1 mRNA expression in chronic phase CML patients in comparison to healthy individuals and no change in SHP-1 mRNA levels after successful TKI treatment. Mutational analysis of the aminoterminal and phosphatase domains of SHP-1 in patients did not reveal genetic lesions. This study also found no correlation of SHP-1 expression at diagnosis with response to treatment, although a trend for lower SHP-1 expression was noted in the very small non-responders' group of the 3-month therapeutic milestone. PMID:26373709

  4. Learning curve: the surgeon as a prognostic factor in colorectal cancer surgery.

    PubMed

    Renzulli, Pietro; Laffer, Urban T

    2005-01-01

    The individual surgeon is an independent prognostic factor for outcome in colorectal cancer surgery. The surgeon's learning curve is therefore directly related to the patient's outcome. The exact shape of the learning curve, however, is unknown. The present study reviewed supervision, training/teaching, specialization, surgeon's caseload, and hospital's caseload as the five main surgeon- and hospital-related confounding factors for outcome, and examined their influence on the learning curve as well as their interactions and prognostic significance. All five confounding factors were related to outcome. The highest degree of evidence, however, was found for training/teaching (introduction of total mesorectal excision), specialization in colorectal surgery (special interest, board-certification, specialized colorectal cancer units), and the surgeon's caseload. Five surgeon- and hospital-related factors directly influence the surgeon's learning curve and are therefore rightly considered predictors of outcome in colorectal cancer surgery. Improvements in supervision, training/teaching, specialization, the surgeon's caseload, and the hospital's caseload will therefore translate into enhanced patient outcome. PMID:15865024

  5. Nuclear fractal dimension as a prognostic factor in oral squamous cell carcinoma.

    PubMed

    Goutzanis, L; Papadogeorgakis, N; Pavlopoulos, P M; Katti, K; Petsinis, V; Plochoras, I; Pantelidaki, C; Kavantzas, N; Patsouris, E; Alexandridis, C

    2008-04-01

    Strong theoretical reasons exist for using fractal geometry in measurements of natural objects, including most objects studied in pathology. Indeed, fractal dimension provides a more precise and theoretically more appropriate approximation of their structure properties and especially their shape complexity. The aim of our study was to evaluate the nuclear fractal dimension (FD) in tissue specimens from patients with oral cavity carcinomas in order to assess its potential value as prognostic factor. Relationships between FD and other factors including clinicopathologic characteristics were also investigated. Histological sections from 48 oral squamous cell carcinomas as well as from 17 non-malignant mucosa specimens were stained with Hematoxylin-Eosin for pathological examination and with Feulgen for nuclear complexity evaluation. The sections were evaluated by image analysis using fractal analysis software to quantify nuclear FD by the box-counting method. Carcinomas presented higher mean values of FD compared to normal mucosa. Well differentiated neoplasms had lower FD values than poorly differentiated ones. FD was significantly correlated with the nuclear size. Patients with FD lower than the median value of the sample had statistically significant higher survival rates. Within the sample of patients studied, FD was proved to be an independent prognostic factor of survival in oral cancer patients. In addition this study provides evidence that there are several statistically significant correlations between FD and other morphometric characteristics or clinicopathologic factors in oral squamous cell carcinomas. PMID:17692559

  6. ERG Expression in Prostate Needle Biopsy: Potential Diagnostic and Prognostic Implications.

    PubMed

    Lee, Sandra L; Yu, Darryl; Wang, Cheng; Saba, Raya; Liu, Shuhong; Trpkov, Kiril; Donnelly, Bryan; Bismar, Tarek A

    2015-08-01

    To investigate the prognostic and diagnostic value of ERG immunohistochemistry (IHC) in prostate needle biopsy when combined with AMACR-CK5/6. ERG IHC was assessed in 119 consecutive prostate needle biopsies where the dual-stain AMACR-CK5/6 IHC was ordered and in 16 cases with a Gleason score (GS) ≥7. IHC results were evaluated in prostate carcinoma (PCA), high-grade prostatic intraepithelial neoplasia (HGPIN), HGPIN with adjacent atypical glands (PINATYP), atypical/suspicious (ASAP) foci, and benign PCA mimickers. GS, HGPIN, extraprostatic extension, perineural invasion, bilateralism of PCA, largest percent of core, and the overall percent of tissue involved by PCA were recorded. ERG was detected in 36% of PCA, 27% of HGPIN, 13% of ATYP/PINATYP, and none of benign mimickers. ERG-positive HGPIN was strongly associated with ERG-positive PCA in the same core compared with ERG-negative HGPIN (P<0.0001). Positive ERG expression in PCA was inversely related to GS and showed trends toward association with higher volume and bilateral disease. ERG was more specific for PCA than AMACR (0.87 vs. 0.23), but less sensitive (0.36 vs. 0.95). In conclusion, ERG IHC is of limited additional diagnostic value when added to AMACR and CK5/6. ERG expression is inversely related to GS and is associated with bilateral involvement and higher PCA tumor volume. ERG-positive HGPIN is strongly associated with the presence of PCA in the same core. Studies investigating the prognostic value of ERG in HGPIN should be implemented to address whether patients with ERG-positive HGPIN are at increased risk for subsequent PCA development. PMID:25517865

  7. HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker12

    PubMed Central

    Sconocchia, Giuseppe; Eppenberger-Castori, Serenella; Zlobec, Inti; Karamitopoulou, Eva; Arriga, Roberto; Coppola, Andrea; Caratelli, Sara; Spagnoli, Giulio Cesare; Lauro, Davide; Lugli, Alessandro; Han, Junyi; Iezzi, Giandomenica; Ferrone, Cristina; Ferlosio, Amedeo; Tornillo, Luigi; Droeser, Raoul; Rossi, Piero; Attanasio, Antonio; Ferrone, Soldano; Terracciano, Luigi

    2014-01-01

    The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1β (IL-1β) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1β production by monocytes. PMID:24563618

  8. Long-Term Follow-Up and Prognostic Factors for Advanced Thymic Carcinoma

    PubMed Central

    Wu, Jun-xin; Chen, Hui-qin; Shao, Ling-dong; Qiu, Su-fang; Ni, Qian-yu; Zheng, Bu-hong; Wang, Jie-zhong; Pan, Jian-ji; Li, Jin-luan

    2014-01-01

    Abstract The aim of this study was to evaluate the long-term survival outcomes in patients with advanced thymic carcinoma and identify prognostic factors influencing the survival. We retrospectively analyzed 90 consecutive patients with pathologically confirmed advanced thymic carcinoma (Masaoka III and IV) in our institute, from December 2000 to 2012. Age, sex, clinical characteristics, laboratory findings, Masaoka and tumor node metastasis staging, pathologic grade, and treatment modalities were analyzed to identify prognostic factors associated with the progress-free survival (PFS) and the overall survival (OS) rates. Statistical analysis was conducted using SPSS, version 19.0 (SPSS, Inc, Chicago, IL). A total of 73 (81.1%) male and 17 (18.9%) female patients participated in the study. The median follow-up time was 75 months (range, 20–158 months). The 5-year PFS and OS rates were 23.6% (95% confidence interval [CI], 14.6%–33.8%) and 35.7% (95% CI, 25.1%–46.4%), respectively. The multivariate Cox regression model analysis showed that factors improving the PFS were the normal lactate dehydrogenase (LDH) level (P < 0.001), Masaoka III stage (P = 0.028), and radiotherapy (RT) (P < 0.001). The LDH (P < 0.001), T stage (P < 0.001), and the pathologic grade (P = 0.047) were independently prognostic of OS. Long-term follow-up of the advanced thymic carcinoma showed poor outcomes of PFS and OS. LDH, Masaoka stage, and RT affected the PFS, and LDH, T stage, and pathologic grade seemed to affect the OS. Establishing a better staging system for predicting outcomes would be warranted. PMID:25526488

  9. Prognostic Factors for Neurologic Outcome in Patients with Carotid Artery Stenting

    PubMed Central

    Hung, Chi-Sheng; Lin, Mao-Shin; Chen, Ying-Hsien; Huang, Ching-Chang; Li, Hung-Yuan; Kao, Hsien-Li

    2016-01-01

    Background Carotid artery stenting (CAS) is a valid treatment for patients with carotid artery stenosis. The long-term outcome and prognostic factors in Asian population after CAS are not clear. This study aimed to identify the prognostic factors among Asian patients who have undergone CAS. Methods We retrospectively analyzed 246 patients with CAS. Annual carotid duplex ultrasound was used to identify restenosis. Peri-procedural complications, restenosis, neurologic outcomes, and mortality were recorded. Cox regression analyses were used to identify prognostic factors. Results The mean follow-up time was 49.2 months. Procedural success was achieved in 237 patients (98.3%), and protection devices were used in 208 patients (84.5%). Within 30 days of CAS, 13 (4.3% per procedure) peri-procedural complications occurred. During the follow-up period, 24 (9.7%) patients developed restenosis, and 37 (15.0%) developed ischemic strokes. In a multiple logistic regression analysis, head and neck radiotherapy [hazard ratio (HR) = 9.9, 95% confidence interval (CI), 3.38-29.1, p < .001], stent diameter (HR = 0.72, 95% CI, 0.58-0.89, p = .003), and predilatation (HR = 3.08 95% CI, 1.21-7.81, p = .018) were independent predictors for restenosis. In Cox regression analysis, hypercholesterolemia (HR = 0.25, 95% CI, 0.07-0.94, p = .04), head and neck radiotherapy (HR = 6.2, 95% CI, 1.8-21.3, p = .004), and restenosis (HR = 3.6, 95% CI, 1.1-11.18, p = .04) were predictors for recurrent ipsilateral ischemic stroke. Conclusions CAS provides reliable long-term results in Asian patients with carotid stenosis. Restenosis is associated with an increased rate of recurrent stroke and should be monitored carefully following CAS. PMID:27122951

  10. Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study

    PubMed Central

    2010-01-01

    Background We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. Methods This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Results Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Conclusion Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered. PMID:21182799

  11. Prognostic factors in children with extracranial germ cell tumors treated with cisplatin-based chemotherapy

    PubMed Central

    Kim, Jinsup; Lee, Na Hee; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Seo, Jeong-Meen; Lee, Suk-Koo

    2015-01-01

    Purpose To evaluate the outcomes and prognostic factors in children with extracranial germ cell tumors (GCTs) treated at a single institution. Methods Sixty-six children diagnosed with extracranial GCTs between 1996 and 2012 were included in the study. Primary treatment was surgical excision, followed by six cycles of cisplatin-based chemotherapy. The survival rates were compared according to the International Germ Cell Cancer Cooperative Group classification used for GCTs in adults to validate the classification guidelines for GCTs in children. Results The median patient age was 4.4 years. In 34 patients (51.5%), the primary tumor site was the gonad. Extragonadal GCTs were detected in 32 patients. The 5-year overall survival and event-free survival (EFS) were 92.0%±3.5% and 90.4%±3.7%, respectively. In univariate analysis, tumor histology, metastasis, and elevated alpha-fetoprotein were not prognostic factors in children with extracranial GCTs. However, EFS was poorer in patients with mediastinal disease (n=12, 66.7%±13.6 %) than in those with nonmediastinal disease (n=54, 96.0%±2.8%) (P=0.001). The 5-year EFS was lower in patients older than 10 years, (n=21, 80.0%±8.9%) compared with those younger than 10 years (n=45, 95.2%±3.3%) (P=0.04). Multivariate analysis identified the mediastinal tumor site as the only independent prognostic factor. Conclusion The prognosis of children with extracranial GCTs was favorable. However, nongerminomatous mediastinal tumors were associated with poor survival in children. Further research is needed to improve the prognosis of children with malignant mediastinal GCTs. PMID:26576183

  12. Estrogen receptor beta as a prognostic factor in breast cancer patients: A systematic review and meta-analysis

    PubMed Central

    Chen, Kai; Su, Fengxi; Song, Erwei; Gong, Chang

    2016-01-01

    Background The prognostic role of estrogen receptor beta (ERβ) in early-stage breast cancer is unclear. We performed a systematic review and meta-analysis to evaluate the prognostic value of ERβ in early-stage breast cancer patients. Method We searched Medline, Embase, and the Web of Science for studies published between 1990 and 2015 that assessed ERβ status in breast cancer patients. A total of 25 studies comprising 9919 patients fitting our inclusion and exclusion criteria were included. The hazard ratios of ERβ status were extracted for diseases free survival (DFS)/) and overall survival (OS). Random or fixed-effects models were used when appropriate, and between-study heterogeneity was assessed. Results In the 20 studies that assessed ERβ status using immunohistochemical (IHC) methods, we observed significantly improved DFS in patients positive for ERβ-1 (HR=0.56, 95%CI 0.40-0.78, P=0.0007) and ERβ-2 (HR=0.67, 95%CI 0.45-1.00, P=0.05). Improved OS was associated with a positive status for pan-ERβ (HR=0.60, 95%CI 0.45-0.80, P=0.0004) and ERβ-2 (HR=0.44, 95%CI 0.31-0.62, P<0.0001). In ERα-positive patients, ERβ positivity was not associated with DFS (HR=0.77, 95%CI 0.46-1.27, P=0.31) or OS (HR=0.64, 95%CI 0.37-1.11, P=0.11). In contrast, ERβ expression was significantly associated with increased DFS (HR=0.37, 95%CI 0.14-0.93, P=0.03) or OS (HR=0.44, 95%CI 0.30-0.65, P<0.0001) in ERα-negative patients. We did not observe an association between ERβ mRNA levels and DFS and OS. Conclusion In this study, we showed that IHC ERβ status, rather than mRNA levels, is a prognostic factor that is associated with DFS and OS in breast cancer patients. The prognostic value of ERβ may be higher in ERα-negative patients than in ERα-positive patients. PMID:26863572

  13. Prognosis and prognostic factors of retinal infarction: a prospective cohort study.

    PubMed Central

    Hankey, G J; Slattery, J M; Warlow, C P

    1991-01-01

    OBJECTIVE--To determine the prognosis and adverse prognostic factors in patients with retinal infarction due to presumed atheromatous thromboembolism or cardiogenic embolism. DESIGN--Prospective cohort study. SETTING--University hospital departments of clinical neurology. PATIENTS--99 patients with retinal infarction, without prior stroke, referred to a single neurologist between 1976 and 1986 and evaluated and followed up prospectively until death or the end of 1986 (mean follow up 4.2 years). INTERVENTIONS--Cerebral angiography (55 patients), aspirin treatment (37), oral anticoagulant treatment (eight), carotid endarterectomy (13), cardiac surgery (six), and peripheral vascular surgery (two). MAIN OUTCOME MEASURES--Death, stroke, coronary events, contralateral retinal infarction; survival analysis confined to 98 patients with retinal infarction due to presumed artheromatous thromboembolism or cardiogenic embolism (one patient with giant cell arteries excluded), and Cox's proportional hazards regression analysis, including age as a prognostic factor. RESULTS--During follow up 29 patients died (21 of vascular causes and eight of non-vascular or unknown causes), 10 had a first ever stroke, 19 had a coronary event, and only one developed contralateral retinal infarction. A coronary event accounted for more than half (59%) of the deaths whereas stroke was the cause of only one death (3%). Over the first five years after retinal infarction the actuarial average absolute risk of death was 8% per year; of stroke 2.5% per year (7.4% in the first year); of coronary events 5.3% per year, exceeding that of stroke; and of stroke, myocardial infarction, or vascular death 7.4% per year. Prognostic factors associated with an increased risk of death were increasing age, peripheral vascular disease, cardiomegaly, and carotid bruit. Adverse prognostic factors for serious vascular events were increasing age and carotid bruit for stroke, and increasing age, cardiomegaly, and carotid

  14. Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic Value

    PubMed Central

    Marisa, Laetitia; de Reyniès, Aurélien; Duval, Alex; Selves, Janick; Gaub, Marie Pierre; Vescovo, Laure; Etienne-Grimaldi, Marie-Christine; Schiappa, Renaud; Guenot, Dominique; Ayadi, Mira; Kirzin, Sylvain; Chazal, Maurice; Fléjou, Jean-François; Benchimol, Daniel; Berger, Anne; Lagarde, Arnaud; Pencreach, Erwan; Piard, Françoise; Elias, Dominique; Parc, Yann; Olschwang, Sylviane; Milano, Gérard; Laurent-Puig, Pierre; Boige, Valérie

    2013-01-01

    Background Colon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses. Methods and Findings Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype–like, normal-like, serrated CC phenotype–like), and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II–III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival

  15. Prognostic value of stromal decorin expression in patients with breast cancer: a meta-analysis

    PubMed Central

    Li, Shuang-Jiang; Chen, Da-Li; Zhang, Wen-Biao; Shen, Cheng

    2015-01-01

    Background Numbers of studies have investigated the biological functions of decorin (DCN) in oncogenesis, tumor progression, angiogenesis and metastasis. Although many of them aim to highlight the prognostic value of stromal DCN expression in breast cancer, some controversial results still exist and a consensus has not been reached until now. Therefore, our meta-analysis aims to determine the prognostic significance of stromal DCN expression in breast cancer patients. Methods PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literatures met out inclusion criteria. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I2 statistic were employed to estimate the level of heterogeneity across the included studies. Sensitivity analysis was conducted to further identify the possible origins of heterogeneity. The publication bias was detected by Begg’s test and Egger’s test. Results There were three English literatures (involving 6 studies) included into our meta-analysis. On the one hand, both the summarized outcomes based on univariate analysis (HR: 0.513; 95% CI: 0.406-0.648; P<0.001) and multivariate analysis (HR: 0.544; 95% CI: 0.388-0.763; P<0.001) indicated that stromal DCN expression could promise the high cancer-specific survival (CSS) of breast cancer patients. On the other hand, both the summarized outcomes based on univariate analysis (HR: 0.504; 95% CI: 0.389-0.651; P<0.001) and multivariate analysis (HR: 0.568; 95% CI: 0.400-0.806; P=0.002) also indicated that stromal DCN expression was positively associated with high disease-free survival (DFS) of breast cancer patients. No significant heterogeneity or publication bias was observed within this meta-analysis. Conclusions The present evidences indicate that high stromal DCN expression can significantly predict the good prognosis in patients with breast cancer. The

  16. KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma.

    PubMed

    Guo, Zhongqiang; Liu, Jin; Zhang, Lian; Su, Boxing; Xing, Yunchao; He, Qun; Ci, Weimin; Li, Xuesong; Zhou, Liqun

    2015-02-01

    Potassium inwardly rectifying channel, subfamily J, member 1 (KCNJ1), as an ATP-dependent potassium channel, plays an essential role in potassium balance. KCNJ1 variation is associated with multiple diseases, such as antenatal Bartter syndrome and diabetes. However, the role of KCNJ1 in clear cell renal cell carcinoma (ccRCC) is still unknown. Here, we studied the expression and function of KCNJ1 in ccRCC. The expression of KCNJ1 was evaluated in ccRCC tissues and cell lines by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry analysis. The relationship between KCNJ1 expression and clinicopathological characteristics was analyzed. p3xFLAG-CMV-14 vector containing KCNJ1 was constructed and used for transfecting ccRCC cell lines 786-O and Caki-2. The effects of KCNJ1 on cell proliferation, invasion, and apoptosis were detected in ccRCC cell lines using cell proliferation assay, transwell assay, and flow cytometry, respectively. We found that KCNJ1 was low-expressed in ccRCC tissues samples and cell lines, and its expression level was significantly associated with tumor pathology grade (P = 0.002) and clinical stage (P = 0.023). Furthermore, the KCNJ1 expression was a prognostic factor of ccRCC patient's survival (P = 0.033). The re-expression of KCNJ1 in 786-O and Caki-2 significantly inhibited cancer cell growth and invasion and promoted cancer cell apoptosis. Moreover, knockdown of KCNJ1 in HK-2 cells promoted cell proliferation. Collectively, these data highlight that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis. PMID:25344677

  17. Correlation of ER, PR and HER-2/Neu with other Prognostic Factors in Infiltrating Ductal Carcinoma of Breast

    PubMed Central

    Siadati, Sepideh; Sharbatdaran, Majid; Nikbakhsh, Novin; Ghaemian, Naser

    2015-01-01

    Background and Objectives: Breast cancer is the most common malignancy among women in the world. The aim of this study was to assess estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu of infiltrating ductal carcinoma (IDC) with tumor size, histologic grade, lymph node metastasis and age. Methods: This study was carried out on 300 tissue blocks of patients with IDC who underwent mastectomy from 2007 to 2011 in Shahid Beheshti Hospital, affiliated to Babol University of Medical Sciences, Babol, Iran. Data including age, tumor size, and histologic grade and lymph node status retrieved from pathology department. Result: The mean age of the patients was 40.2±2.3 (ranged 19-82 years). ER and PR were positively correlated with each other ( P = 0.001) and they inversely correlated with HER-2/neu ( P =0.001). We observed correlation between ER and PR expression and low histologic grade ( P = 0.001) and HER-2/neu expression and high histologic grade ( P = 0.003). There was correlation between HER-2/neu expression and lymph node involvement ( P =0.03). None of these makers showed correlation with age and tumor size ( P > 0.05). Conclusion: Our findings indicate the importance of ER, PR and HER-2/neu expression as prognostic factors for therapeutic decision. PMID:26351488

  18. Expression and Prognostic Significance of a Panel of Tissue Hypoxia Markers in Head-and-Neck Squamous Cell Carcinomas

    SciTech Connect

    Le, Quynh-Thu Kong, Christina; Lavori, Phillip W.; O'Byrne, Ken; Erler, Janine T.; Huang Xin; Chen Yijun; Cao Hongbin; Tibshirani, Robert; Denko, Nic; Giaccia, Amato J.; Koong, Albert C.

    2007-09-01

    Purpose: To investigate the expression pattern of hypoxia-induced proteins identified as being involved in malignant progression of head-and-neck squamous cell carcinoma (HNSCC) and to determine their relationship to tumor pO{sub 2} and prognosis. Methods and Materials: We performed immunohistochemical staining of hypoxia-induced proteins (carbonic anhydrase IX [CA IX], BNIP3L, connective tissue growth factor, osteopontin, ephrin A1, hypoxia inducible gene-2, dihydrofolate reductase, galectin-1, I{kappa}B kinase {beta}, and lysyl oxidase) on tumor tissue arrays of 101 HNSCC patients with pretreatment pO{sub 2} measurements. Analysis of variance and Fisher's exact tests were used to evaluate the relationship between marker expression, tumor pO{sub 2}, and CA IX staining. Cox proportional hazard model and log-rank tests were used to determine the relationship between markers and prognosis. Results: Osteopontin expression correlated with tumor pO{sub 2} (Eppendorf measurements) (p = 0.04). However, there was a strong correlation between lysyl oxidase, ephrin A1, and galectin-1 and CA IX staining. These markers also predicted for cancer-specific survival and overall survival on univariate analysis. A hypoxia score of 0-5 was assigned to each patient, on the basis of the presence of strong staining for these markers, whereby a higher score signifies increased marker expression. On multivariate analysis, increasing hypoxia score was an independent prognostic factor for cancer-specific survival (p = 0.015) and was borderline significant for overall survival (p = 0.057) when adjusted for other independent predictors of outcomes (hemoglobin and age). Conclusions: We identified a panel of hypoxia-related tissue markers that correlates with treatment outcomes in HNSCC. Validation of these markers will be needed to determine their utility in identifying patients for hypoxia-targeted therapy.

  19. Evaluating the Prevalence of the Epidermal Growth Factor Receptor in Transitional Cell Carcinoma of Bladder and its Relationship With Other Prognostic Factors

    PubMed Central

    Parvin, Mahmoud; Sabet-Rasekh, Parto; Hajian, Parastoo; Mohammadi Torbati, Peyman; Sabet-Rasekh, Parisa; Mirzaei, Hamidreza

    2016-01-01

    Background: The most common malignancy in the urinary system has been bladder cancer and the most predominant histologic subtype has been transitional cell carcinoma (TCC). There were many molecular risk factors, related with poor prognosis. One of these factors was expression of epidermal growth factor receptor (EGFR). Objectives: The aim of this study was to evaluate the prevalence of the epidermal growth factor receptor in transitional cell carcinoma of bladder and its relationship with other prognostic factors. Patients and Methods: This analytic descriptive study has performed with 61 patients with TCC of bladder after radical cystectomy whom have been hospitalized in Labbafinejad hospital in Tehran, Iran between 2007 and 2010. We have used Chi-square and t-test to analyze our data samples. Results: Records of 61 patients have studied. Fifty three of the total samples were positive for EGFR expression (86.9%). Fifty samples of these fifty-three belonged to men and three others were women’s samples (P = 0.46). Among the group with EGFR expression the results were as follows: 25 patients (47.2%) were 60 years old or less and 28 patients (52.8%) were older than 60 (P = 0.023), 16 patients (30.2%) had invasion to lamina properia, and the rest of them had invasion to deeper layers (P = 0.56). For most patients we could not determine the invasion of tumoral cells into the lymph nodes (Nx) (P = 0.067). Thirty four patients (64.2%) had not lymphovascular invasion (P = 0.44) and in forty three of patients (81.1%), perineural invasion have not seen (P = 0.23). Finally, 36 patients (67.9%) were grade 3 (P = 0.27). Conclusions: In this study we have concluded that most patients had EGFR positive expression. Also, except for the age, there was not any significant relation between expression of EGFR and the other prognostic factors such as, gender, invasion of the tumor into the layers, involving the lymph nodes, lymphovascular or perineural invasion, and grading. PMID

  20. Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

    SciTech Connect

    Patel, Samir; Portelance, Lorraine . E-mail: lorraine.portelance@muhc.mcgill.ca; Gilbert, Lucy; Tan, Leonard; Stanimir, Gerald; Duclos, Marie; Souhami, Luis

    2007-08-01

    Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.

  1. Stromal CD4/CD25 positive T-cells are a strong and independent prognostic factor in non-small cell lung cancer patients, especially with adenocarcinomas.

    PubMed

    Kayser, Gian; Schulte-Uentrop, Luzie; Sienel, Wulf; Werner, Martin; Fisch, Paul; Passlick, Bernward; Zur Hausen, Axel; Stremmel, Christian

    2012-06-01

    Within the concert of immune reactions against tumour cells cytotoxic and regulatory T-cells are of utmost importance. Several studies revealed contradictory results on this issue. We therefore focused on functional expression patterns and localization of tumour-infiltrating T-lymphocytes in non-small cell lung cancer (NSCLC) and their impact on patient's survival. 232 curatively operated NSCLC patients were included. After histological reevaluation and construction of tissue-multi-arrays immunohistochemical doublestains for CD3/CD8 and CD4/CD25 were performed to evaluate the total number of T-cells and their subsets of cytotoxic and activated T-cells. Additionally, the localization of the lymphocytes was included in the analysis. Hereby, T-cells within the tumour stroma were regarded as stromal, those among cancer cells as intraepithelial. The number of lymphocytes differed significantly between the histological subtypes being most prominent in large cell carcinomas. Survival analysis showed that high numbers of stromal T-lymphocytes are of beneficial prognostic influence in NSCLC patients. This also proved to be an independent prognostic factor in adenocarcinomas. Thus, in a large and well characterized cohort of NSCLC this is the first study to determine the prognostic value of stromal T-lymphocytes, as these are an independent prognosticator in NSCLC especially in adenocarcinomas whereas intraepithelial T-cells are not. PMID:22300751

  2. Aromatase and estrogen receptor alpha mRNA expression as prognostic biomarkers in patients with astrocytomas.

    PubMed

    Dueñas Jiménez, J M; Candanedo Arellano, A; Santerre, A; Orozco Suárez, S; Sandoval Sánchez, H; Feria Romero, I; López-Elizalde, R; Alonso Venegas, M; Netel, B; de la Torre Valdovinos, B; Dueñas Jiménez, S H

    2014-09-01

    Estrogens are oncogenic hormones at a high level in breast, prostate, endometrial and lung cancer. Estrogens are synthesized by aromatase which has been used as a biomarker both in breast and lung cancer. Estrogen biological activities are executed by their classic receptors (ERα and ERβ). ERα has been described as a cancer promoter and ERβ, as a possible tumor suppressor. Both receptors are present at low levels in primary multiforme glioblastoma (GBM). The GBM frequency is 50 % higher in men than in women. The GBM patient survival period ranges from 7 to 18 months. The purpose of this pilot study was to evaluate aromatase and estrogen receptor expression, as well as 17ß-estradiol concentration in astrocytoma patients biopsies to obtain a prognosis biomarker for these patients. We analyzed 36 biopsies of astrocytoma patients with a different grade (I-IV) of malignity. Aromatase and estrogen receptor mRNA expression were analyzed by semiquantitative RT-PCR, and the E2 levels, by ELISA. E2 concentration was higher in GBM, compared to grade II or III astrocytomas. The number of cells immunoreactive to aromatase and estrogen receptors decreased as the grade of tumor malignity increased. Aromatase mRNA expression was present in all biopsies, regardless of malignity grade or patient age or gender. The highest expression of aromatase mRNA in GBM patients was associated to the worst survival prognostic (6.28 months). In contrast lowest expression of ERα mRNA in astrocytoma patients had a worst prognosis. In conclusion, aromatase and ERα expression could be used as prognosis biomarkers for astrocytoma patients. PMID:25005528

  3. Prognostic Factors and Survival in Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy

    PubMed Central

    Crvenkova, Simonida

    2015-01-01

    BACKGROUND: According to the literature, performance status, stage-tumor dimension and nodal status, weight loss, were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer. AIM: To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy. MATERIAL AND METHODS: In the study 85 patients were randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy (RT). In the second concurrent group, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal three dimensional (3-D) RT. RESULTS: From October 2005 to March 2008, 93 patients were enrolled. Eight patients were not eligible, seven had stage IV and one patient had pleural effusion. They were all initially considered to have stage IIIB disease. The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method: - age, p<0.05; - performant status, p<0.001; - weight loss, p<0.001; tumor dimension, p<0.05; and - nodal involvement, p<0.05. CONCLUSION: In our study, the dose-limiting toxicity, esophagitis was reduced by performing conformal radiotherapy. Conformal thoracic radiotherapy and new radiotherapy technics, such as respiratory gated

  4. Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

    SciTech Connect

    Daniels, Thomas B.; Brown, Paul D.; Felten, Sara J.; Wu, Wenting; Buckner, Jan C.; Arusell, Robert M.; Curran, Walter J.; Abrams, Ross A.; Schiff, David; Shaw, Edward G.

    2011-09-01

    Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of

  5. The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ERα, and is an independent prognostic factor in node-negative breast cancer.

    PubMed

    Brennan, D J; O'Connor, D P; Laursen, H; McGee, S F; McCarthy, S; Zagozdzon, R; Rexhepaj, E; Culhane, A C; Martin, F M; Duffy, M J; Landberg, G; Ryden, L; Hewitt, S M; Kuhar, M J; Bernards, R; Millikan, R C; Crown, J P; Jirström, K; Gallagher, W M

    2012-07-26

    Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n=690; P=0.002, 0.013). We also show that CART increases the transcriptional activity of ERα in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. PMID:22139072

  6. Meta-analysis of the prognostic value of abnormally expressed lncRNAs in hepatocellular carcinoma

    PubMed Central

    Qu, Zhen; Yuan, Chun-Hui; Yin, Chang-Qing; Guan, Qing; Chen, Hao; Wang, Fu-Bing

    2016-01-01

    Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People’s Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20–2.34, P=0.002; I2=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65–2.61, P<0.001; I2=24.0%, P=0.215), while no association was observed with disease-free survival of HCC patients (HR: 1.39, 95% CI: 0.51–3.78, P=0.524; I2=81.3%, P=0.005). Subgroup analysis further showed that lncRNA transcription level was significantly associated with tumor size (relative risk [RR]: 1.19, 95% CI: 1.01–1.39, P=0.035), microvascular invasion (RR: 1.44, 95% CI: 1.10–1.89, P=0.009), and portal vein tumor thrombus (RR: 1.50, 95% CI: 1.03–2.20, P=0.036). Publication bias and sensitivity analysis further confirmed the stability of our results. Our present meta-analysis indicates that abnormal lncRNA transcription level may serve as a promising indicator for prognostic evaluation of patients with HCC in People’s Republic of China. PMID:27574455

  7. Meta-analysis of the prognostic value of abnormally expressed lncRNAs in hepatocellular carcinoma.

    PubMed

    Qu, Zhen; Yuan, Chun-Hui; Yin, Chang-Qing; Guan, Qing; Chen, Hao; Wang, Fu-Bing

    2016-01-01

    Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People's Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20-2.34, P=0.002; I (2)=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65-2.61, P<0.001; I (2)=24.0%, P=0.215), while no association was observed with disease-free survival of HCC patients (HR: 1.39, 95% CI: 0.51-3.78, P=0.524; I (2)=81.3%, P=0.005). Subgroup analysis further showed that lncRNA transcription level was significantly associated with tumor size (relative risk [RR]: 1.19, 95% CI: 1.01-1.39, P=0.035), microvascular invasion (RR: 1.44, 95% CI: 1.10-1.89, P=0.009), and portal vein tumor thrombus (RR: 1.50, 95% CI: 1.03-2.20, P=0.036). Publication bias and sensitivity analysis further confirmed the stability of our results. Our present meta-analysis indicates that abnormal lncRNA transcription level may serve as a promising indicator for prognostic evaluation of patients with HCC in People's Republic of China. PMID:27574455

  8. The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors.

    PubMed

    Tihan, Tarik; Zhou, Tianni; Holmes, Emi; Burger, Peter C; Ozuysal, Sema; Rushing, Elisabeth J

    2008-02-01

    We performed a retrospective analysis of 96 pediatric posterior fossa ependymomas in order to determine the prognostic value of histological grade based on the current WHO grading scheme. The patients were selected among Children's Oncology Group (previously Pediatric Oncology Group-POG) patients enrolled in clinical trials, and on the basis of central pathology review, location, and age. We excluded entities such as sub-ependymoma, myxopapillary, or clear-cell ependymoma, after a consensus diagnosis by three neuropathologists. A total of 66 males and 30 females with a median age of 48 months were identified. The group was analyzed to determine the effects of histological grade, age, gender, and extent of resection on event-free and overall survival. Our results showed that extent of resection, age, and histological grade were independent prognostic variables for event-free survival. The relative risk for extent of resection and histological grade was calculated as 3.59 (P<0.001) and 3.58 (P<0.001), respectively. Overall survival significantly correlated with extent of resection and age, but not with histological grade. We compared our results with peer-reviewed publications on pediatric intracranial ependymomas in the English language between 1990 and 2005. Selection criteria identified 32 manuscripts involving 1444 patients. Extent of resection was a significant factor in 21, age in 12, and histological grading in nine of these studies. Other factors reported to be significant by more than one study included tumor location and radiation treatment. Our findings suggest that histological grade (WHO Grade II vs III) is an independent prognostic indicator for event-free survival, but may not be so for overall survival in pediatric posterior fossa ependymomas. We believe that an accurate assessment of the prognostic value of histological grade depends on the selection of a well-characterized clinical cohort of sufficient size, and the inclusion of relevant

  9. MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer

    PubMed Central

    2014-01-01

    Background MicroRNAs(miRNAs) are small non-coding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-378 has been found in some types of cancer. However, effects and potential mechanisms of miR-378 in colorectal cancer (CRC) have not been explored. Methods Quantitative RT-PCR was performed to evaluate miR-378 levels in CRC cell lines and 84 pairs of CRC cancer and normal adjacent mucosa. Kaplan–Meier and Cox proportional regression analyses were utilized to determine the association of miR-378 expression with survival of patients. MTT and invasion assays were used to determine the role of miR-378 in regulation of CRC cancer cell growth and invasion, respectively. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Luciferase assay was performed to assess miR-378 binding to vimentin gene. Results In this study, we confirmed that miR-378 significantly down-regulated in CRC cancer tissues and cell lines. Moreover, patients with low miR-378 expression had significantly poorer overall survival, and miR-378 expression was an independent prognostic factor in CRC. Over-expression of miR-378 inhibited SW620 cell growth and invasion, and resulted in down-regulation of vimentin expression. However, miR-378 knock-down promoted these processes and enhanced the expression of vimentin. In addition, we further identified vimentin as the functional downstream target of miR-378 by directly targeting the 3′-UTR of vimentin. Conclusions In conclusion, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion. Our present results implicate the potential effects of miR-378 on prognosis and treatment of CRC cancer. PMID:24555885

  10. Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ

    PubMed Central

    Nakamichi, Ikuo; Yamashita, Yoshihiro; Yamamoto, Noriaki; Yamauchi, Kensuke; Nogami, Shinnosuke; Kaneuji, Takeshi; Mitsugi, Sho; Tanaka, Kenkou; Kataoka, Yoshihiro; Sakurai, Takuma; Kiyomiya, Hiroyasu; Miyamoto, Ikuya; Takahashi, Tetsu

    2014-01-01

    Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital. Patients and Methods: This single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlying risk factors, clinical features, location and bone marker levels of BRONJ. Results: The mean BRONJ remission rate was 57.6%, and the median duration of remission was seven months. Eighteen patients (34.6%) had persistent or progressive disease with a recommended conservative treatment for BRONJ. Notably, urinary cross-linked N-terminal telopeptide of type 1 collagen (NTX) levels in those resistant to conservative treatment tended to be lower than in patients that healed well. Conclusions: We confirm that a significant proportion of BRONJ sufferers are refractory to a recommended conservative treatment and find that anticancer drugs, periodontal disease, the level of bone exposure and the dosage of intravenous BPs (e.g. zoledronate) represent specific risk factors in BRONJ that may determine the success of a recommended conservative treatment. Additionally, the NTX levels might be able to be a prognostic factor for the conservative treatment of BRONJ; additional research is necessary. Key words:Bisphosphonate, osteonecrosis, jaw, prognostic, retrospective. PMID:24596631

  11. Promoter Methylation of PTEN Is a Significant Prognostic Factor in Melanoma Survival.

    PubMed

    Roh, Mi Ryung; Gupta, Sameer; Park, Kyu-Hyun; Chung, Kee Yang; Lauss, Martin; Flaherty, Keith T; Jönsson, Göran; Rha, Sun Young; Tsao, Hensin

    2016-05-01

    Structural compromise of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), occurs in 10% of melanoma specimens, and loss of PTEN expression through DNA methylation of the PTEN promoter region has also been reported in a number of other malignancies. However, the role of PTEN promoter methylation in melanoma is not well understood. We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features, and its impact on the outcome of patients with melanoma. PTEN promoter methylation data were acquired from an archived primary Korean melanoma cohort (KMC) of 158 patients and, for validation, 234 patients from The Cancer Genome Atlas melanoma (TCGA-MEL) cohort. Hierarchical clustering was performed to identify PTEN "high methylated" and "low methylated" samples. Subsequently, differences in clinical features and outcomes based on PTEN promoter methylation status were then analyzed using SPSS and R. In the KMC, all tumors were acquired from primary tumors and 65.7% (n = 105) were acral or mucosal by site, whereas in the TCGA-MEL cohort, 90.5% of the tumors were from regional lymph node and distant metastatic lesions. Overall, 17.7% and 45.7% of the specimens harbored BRAF mutations in the KMC and TCGA-MEL cohort, respectively. Neuroblastoma RAS viral oncogene homolog was mutated in 12.2% and 26.9% of the tumors in the KMC and TCGA-MEL cohort, respectively. In the KMC, 31 cases (19.6%) were included in the high methylated group versus 142 cases (60.7%) in the TCGA-MEL cohort (P < 0.001). Multivariate Cox-regression analysis revealed promoter methylation of PTEN to be an independent negative prognostic factor for survival in both the KMC (hazard ratio 3.76, 95% confidence interval = 1.24-11.12, P = 0.017) and TCGA-MEL cohort (HR 1.88, 95% confidence interval = 1.13-3.12, P = 0.015). Our results indicate that PTEN promoter methylation is an independent predictor for impaired survival in

  12. Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1: A Prospective Study

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J.; Jensen, Robert T.

    2013-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking. To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled

  13. Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Ban, Wooho; Lee, Jong Min; Ha, Jick Hwan; Yeo, Chang Dong; Kang, Hyeon Hui; Rhee, Chin Kook; Moon, Hwa Sik

    2016-01-01

    Purpose To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). Materials and Methods From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. Results In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival. Conclusion Dyspnea could be a significant prognostic factor in patients with NSCLC. PMID:27401635

  14. A prospective study on MRI findings and prognostic factors in athletes with MTSS.

    PubMed

    Moen, M H; Schmikli, S L; Weir, A; Steeneken, V; Stapper, G; de Slegte, R; Tol, J L; Backx, F J G

    2014-02-01

    In medial tibial stress syndrome (MTSS) bone marrow and periosteal edema of the tibia on the magnetic resonance imaging (MRI) is frequently reported. The relationship between these MRI findings and recovery has not been previously studied. This prospective study describes MRI findings of 52 athletes with MTSS. Baseline characteristics were recorded and recovery was related to these parameters and MRI findings to examine for prognostic factors. Results showed that 43.5% of the symptomatic legs showed bone marrow or periosteal edema. Absence of periosteal and bone marrow edema on MRI was associated with longer recovery (P = 0.033 and P = 0.013). A clinical scoring system for sports activity (SARS score) was significantly higher in the presence of bone marrow edema (P = 0.027). When clinical scoring systems (SARS score and the Lower Extremity Functional Scale) were combined in a model, time to recovery could be predicted substantially (explaining 54% of variance, P = 0.006). In conclusion, in athletes with MTSS, bone marrow or periosteal edema is seen on MRI in 43,5% of the symptomatic legs. Furthermore, periosteal and bone marrow edema on MRI and clinical scoring systems are prognostic factors. Future studies should focus on MRI findings in symptomatic MTSS and compare these with a matched control group. PMID:22515327

  15. Myelopathy Caused by Soft Cervical Disc Herniation : Surgical Results and Prognostic Factors

    PubMed Central

    Kim, Young-Jin; Yi, Hyeong-Joong; Kim, Young-Soo; Ko, Yong; Oh, Suck Jun

    2007-01-01

    Objective The purpose of this study was to investigate the surgical results and prognostic factors for patients with soft cervical disc herniation with myelopathy. Methods During the last 7 years, 26 patients with cervical discogenic myelopathy were undertaken anterior discectomy and fusion. Clinical and radiographic features were reviewed to evaluate the surgical results and prognostic factors. The clinical outcome was judged using two grading systems (Herkowitz's scale and Nurick's grade). Results Male were predominant (4:1), and C5-6 was the most frequently involved level. Gait disturbance, variable degree of spasticity, discomfort in chest and abdomen, hand numbness were the most obvious signs. Magnetic resonance(MR) images showed that central disc herniation was revealed in 16 cases, and accompanying cord signal changes in 4. Postoperatively, 23 patients showed favorable results (excellent, good and fair) according to Herkowitz's scale. Conclusion Anterior cervical discectomy and fusion effectively reduced myelopathic symptoms due to soft cervical disc herniation. The authors assured that the shorter duration of clinical attention, the lesser the degree of myelopathy and better outcome in discogenic myelopathy. PMID:19096586

  16. Prognostic Factors for Distant Metastasis in Patients with Locoregional Recurrence after Mastectomy

    PubMed Central

    Jeong, Yuri; Gong, Gyungyub; Lee, Hee Jin; Ahn, Sei Hyun; Son, Byung Ho; Lee, Jong Won; Choi, Eun Kyung; Lee, Sang-wook; Ahn, Seung Do

    2015-01-01

    Purpose The purpose of this study was to identify patients with high risk of distant metastasis (DM) after salvage treatment for postmastectomy locoregional recurrence (LRR). Methods We retrospectively reviewed 142 patients who received salvage radiotherapy with or without wide excision for isolated LRR after mastectomy between January 1999 and December 2012. Distant metastasis-free survival (DMFS) was estimated from the date of diagnosis of isolated LRR to the date of DM or last follow-up using the Kaplan-Meier method, and Cox regression analysis was performed to identify prognostic factors for DM. Results The median follow-up period was 54 months. The major failure pattern was DM (56%) and the 5-year DMFS was 43%. In multivariate analysis, initial N (iN) stage, recurrent N (rN) stage, and hormone receptor (HR) status were significant prognostic factors for DM (5-year DMFS: iN0 vs. iN1-3, 73% vs. 25%, p<0.001; rN0 vs. rN1-3, 61% vs. 29%, p<0.001; HR+ vs. HR-, 49% vs. 21%, p<0.001). Conclusion Patients with lymph node involvement and/or HR- specimens seem to experience more DM than patients with chest wall-only recurrence and HR+ specimens. Further studies are needed to investigate the role of chemotherapy in these patients. PMID:26472979

  17. Pre-morbid Type 2 Diabetes Mellitus is not a prognostic factor in ALS

    PubMed Central

    Paganoni, Sabrina; Hyman, Theodore; Shui, Amy; Allred, Peggy; Harms, Matthew; Liu, Jingxia; Maragakis, Nicholas; Schoenfeld, David; Yu, Hong; Atassi, Nazem; Cudkowicz, Merit; Miller, Timothy M.

    2015-01-01

    Objective To determine whether history of pre-morbid type 2 diabetes mellitus (DM2) is a prognostic factor in amyotrophic lateral sclerosis (ALS). Methods The relationship between DM2 and survival was analyzed in a study population consisting of 1,322 participants from six clinical trials. Results Survival did not differ by diabetes status (Log-Rank Test, p=0.98), but did differ by body mass index (BMI) (Log-Rank Test, p=0.008). In multivariate analysis, there was no significant association between diabetes and survival (p=0.18), but the risk of reaching a survival endpoint decreased by 4% for each unit increase in baseline BMI (HR 0.96, 95% CI 0.94–0.99, p=0.001). DM2 was less prevalent among ALS clinical trial participants than predicted. Conclusions History of pre-morbid DM2 is not an independent prognostic factor in ALS clinical trial databases. The low DM2 prevalence rate should be examined in a large, prospective study to determine whether DM2 affects ALS risk. PMID:25900666

  18. Prognostic factors after hepatic resection for the single hepatocellular carcinoma larger than 5 cm

    PubMed Central

    Noh, Ji Hyun; Kim, Tae-Seok; Ahn, Keun Soo; Kim, Yong Hoon

    2016-01-01

    Purpose This study aimed to determine which factors affect the prognosis of hepatectomy for hepatocellular carcinoma (HCC) larger than 5 cm, including the prognostic difference between tumor sizes from 5–10 cm and larger than 10 cm. Methods The medical records of 114 patients who underwent hepatectomy for single HCC larger than 5 cm were reviewed and analyzed retrospectively. Results In the analysis of the entire cohort of 114 patients, the 5-year overall and diseases-free survival rates were 50% and 29%, respectively. In a comparison of survival rates between groups, tumor sizes of 5 to 10 cm and larger than 10 cm, the overall and disease-free survival rates were not significantly different, respectively (54% vs. 41%, P = 0.433 and 33% vs. 23%, P = 0.083). On multivariate analysis, positive hepatitis B, high prothrombin induced by vitamin K absence or antagonist-II levels over 200 mIU/mL, and vascular invasion (micro- and macrovascular invasion) were independent prognostic factors for recurrence after hepatic resection. However, tumor size larger than 10 cm was not significant for recurrence after resection. Conclusion This study shows that surgical resection of solitary HCC larger than 5 cm showed favorable overall survival. And there is no survival difference with tumors between 5–10 cm and larger than 10 cm.

  19. Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis.

    PubMed

    Hales, Russell K; Shokek, Ori; Burger, Peter C; Paynter, Nina P; Chaichana, Kaisorn L; Quiñones-Hinojosa, Alfredo; Jallo, George I; Cohen, Kenneth J; Song, Danny Y; Carson, Benjamin S; Wharam, Moody D

    2010-08-01

    To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis

  20. Prognostic relevance of estrogen receptor α, β and aromatase expression in non-small cell lung cancer.

    PubMed

    Skjefstad, Kaja; Grindstad, Thea; Khanehkenari, Mehrdad Rakaee; Richardsen, Elin; Donnem, Tom; Kilvaer, Thomas; Andersen, Sigve; Bremnes, Roy M; Busund, Lill-Tove; Al-Saad, Samer

    2016-09-01

    Sex steroids and their receptors are important in the fetal development of normal lung tissue. In addition emerging evidence reveals their significance in lung cancer pathogenesis. This encourages the exploitation of hormone receptors as treatment targets in lung cancer, as it has been successfully used in breast cancer. This study investigates the prognostic impact of estrogen receptor (ER) α and β and the aromatase (AR) enzyme in non-small cell lung cancer (NSCLC) patients. Tumor tissue from 335 NSCLC patients was collected and tissue microarrays (TMAs) were constructed. Immunohistochemical analyses were performed to evaluate the expression of ERα, ERβ and AR in the cytoplasme and nuclei of cells in the tumor epithelial and stromal compartment. By use of survival statistics we investigated the markers impact on disease-specific survival (DSS). Nuclear ERβ expression in tumor epithelial cells in female patients (HR 3.03; 95% CI 1.39-6.61) and tumor cell AR expression in all patients (HR 1.55; 95% CI 1.08-2.23) were significant negative prognostic markers of disease-specific survival in our cohort. High ERβ expression correlates with worse outcome in female patients. Further, patients with high AR expression had an unfavorable prognostic outcome compared with patients expressing low AR levels. These results emphasize the importance of sex steroids role in NSCLC, and, as anti-hormonal drugs are widely available, could lead to the development of novel palliative or even adjuvant treatment strategies in this patient population. PMID:27234503

  1. Reduced impact of nodal metastases as a prognostic factor for tonsil cancer in the HPV era.

    PubMed

    Vila, Peter M; Stucken, Chaz L; Morris, Luc G T; Posner, Marshall R; Genden, Eric M; Boffetta, Paolo; Sikora, Andrew G

    2014-09-01

    Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 were obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988 to 1997 as the pre-HPV cohort (N = 752), and 1998-2007 as the HPV-predominant cohort (N = 2,755). Comparing the two cohorts, Kaplan-Meier 5-year overall survival (OS) for tonsil SCC improved from 54.0 to 74.3 % (p < 0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9 % (p < 0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7 %, p < 0.0001), two to three (54.2 vs. 75.9 %, p < 0.0001), four to eight (40.3 vs. 68.9 %, p < 0.0001), and greater than eight positive nodes (25.5 vs. 41.9 %, p < 0.0001). While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from "classical" OPC, with unique prognostic features. PMID:24190760

  2. Reduced Impact of Nodal Metastases as a Prognostic Factor for Tonsil Cancer in the HPV Era

    PubMed Central

    Vila, Peter M.; Stucken, Chaz L.; Morris, Luc G.T.; Posner, Marshall R.; Genden, Eric M.; Boffetta, Paolo; Sikora, Andrew G.

    2013-01-01

    Objective Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Methods Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 was obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988–1997 the pre-HPV cohort (N=752), and 1998–2007 as the HPV-predominant cohort (N=2,755). Results Comparing the two cohorts, Kaplan-Meier five-year overall survival (OS) for tonsil SCC improved from 54.0% to 74.3% (p<0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9% (p<0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7%, p<0.0001), two to three (54.2 vs. 75.9%, P<0.0001), four to eight (40.3 vs. 68.9%, p<0.0001), and greater than eight positive nodes (25.5 vs. 41.9%, p<0.0001). Conclusion While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from “classical” OPC, with unique prognostic features. PMID:24190760

  3. Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

    PubMed Central

    Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

    2008-01-01

    Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464

  4. High Myeloperoxidase Positive Cell Infiltration in Colorectal Cancer Is an Independent Favorable Prognostic Factor

    PubMed Central

    Eppenberger-Castori, Serenella; Zlobec, Inti; Viehl, Carsten T.; Frey, Daniel M.; Nebiker, Christian A.; Rosso, Raffaele; Zuber, Markus; Amicarella, Francesca; Iezzi, Giandomenica; Sconocchia, Giuseppe; Heberer, Michael; Lugli, Alessandro; Tornillo, Luigi; Oertli, Daniel

    2013-01-01

    Background Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). Methods A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. Results MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO−. Conclusions High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC. PMID:23734221

  5. Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010)

    PubMed Central

    Achermann, Christof; Stenner, Frank; Rothschild, Sacha I.

    2016-01-01

    In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have a largely better outcome than those who have less exposure to these agents. The value of the prognostic scores developed by Motzer and Heng is fully reflected by the outcomes according to prognostic risk groups in our unselected patient cohort. Also, the use of surgical intervention appears to be an important prognostic factor, however with a somehow diminished effect by novel systemic therapies. The importance of multiple lines of targeted therapies is underlined by this retrospective analysis. For patients with metastatic RCC not receiving targeted therapy the median OS was 22.6 months compared to those with one TKI 25.4 months. Patients receiving a second-line therapy (median overall survival 27.6 months) and those patients with three or more lines of therapy (43.8 months) have the greatest benefit. Also, exposure to a mTORi improves survival versus non-exposure to mTORi (63.3 vs. 22.3 months, p=0.038). In conclusion a trend towards improved survival is confirmed for an unselected population when the full variety of therapeutic options is available and can be used for the individual patient. PMID:27313782

  6. Low RBM3 Protein Expression Correlates with Clinical Stage, Prognostic Classification and Increased Risk of Treatment Failure in Testicular Non-Seminomatous Germ Cell Cancer

    PubMed Central

    Olofsson, Sven-Erik; Nodin, Björn; Gaber, Alexander; Eberhard, Jakob; Uhlén, Mathias; Jirström, Karin; Jerkeman, Mats

    2015-01-01

    Background Expression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate with favourable clinicopathological parameters and prognosis in several cancer diseases. The aim of this study was to examine the expression and prognostic ability of RBM3 in patients with testicular non-seminomatous germ cell tumours (NSGCT). Patients and Methods Immunohistochemical RBM3 expression was analysed in tissue microarrays with tumours from 206 patients. Chi-square test was applied to analyze associations between RBM3 expression and clinicopathological parameters. Kaplan-Meier analysis was used to assess the impact of RBM3 expression on cancer-specific survival (CSS) and failure-free survival (FFS). Cox regression proportional hazards models were used to estimate the relative risk for failure. Results In the entire cohort, there was a significant association between clinical stage (p=0.044) and RBM3 expression. Weak RBM3 expression correlated with a significantly reduced FFS [79.3% versus 90.4% (p=0.019)] and CSS [87.5% versus 97.3% (p=0.047)]. For patients with metastatic disease (n = 88), significant associations were found between RBM3 expression and IGCCC group (p=0.007). The FFS was significantly inferior for patients with low tumour-specific RBM3 expression [59.3% versus 79.0% (p=0.013)], and this association remained significant in a multivariable model for patients with metastatic disease (HR=3.67; 95% CI 1.14, 11.89). Conclusion Low RBM3 expression is an independent predictor of treatment failure in metastatic NSGCT, in relation to the prognostic factors included in the International Germ Cell Consensus Classification (IGCCC). These findings suggest that RBM3 may be a potential biomarker for treatment stratification in patients with metastatic non-seminomatous germ cell tumours, and therefore merit further validation. PMID:25811459

  7. Functional Analysis of Prognostic Gene Expression Network Genes in Metastatic Breast Cancer Models

    PubMed Central

    Geiger, Thomas R.; Ha, Ngoc-Han; Faraji, Farhoud; Michael, Helen T.; Rodriguez, Loren; Walker, Renard C.; Green, Jeffery E.; Simpson, R. Mark; Hunter, Kent W.

    2014-01-01

    Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+) breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease. PMID:25368990

  8. Increased C-kit intensity is a poor prognostic factor for progression-free and overall survival in patients with newly diagnosed AML.

    PubMed

    Advani, Anjali S; Rodriguez, Cristina; Jin, Tao; Jawde, Rony Abou; Saber, Wael; Baz, Rachid; Kalaycio, Matt; Sobecks, Ronald; Sekeres, Mikkael; Tripp, Barbara; Hsi, Eric

    2008-06-01

    C-kit, a tyrosine kinase receptor, is expressed on most myeloid blasts and is thought to be important in the pathogenesis of AML. Activation of the c-kit receptor leads to phosphorylation and activation of downstream signaling proteins, which are important for cell survival and proliferation. Here, we discuss the prognostic impact of c-kit intensity, measured using the mean fluorescent index (MFI) in patients with newly diagnosed AML. On multivariate analysis, c-kit MFI>20.3 correlated with a decreased progression-free survival and overall survival, independent of known prognostic factors (age, white blood count at diagnosis and cytogenetics). Whether inhibiting c-kit in patients with AML will alter prognosis is the basis of ongoing clinical trials. PMID:17928050

  9. A novel sialyl LeX expression score as a potential prognostic tool in colorectal cancer

    PubMed Central

    2012-01-01

    Background Treatment decisions in colorectal cancer subsequent to surgery are based mainly on the TNM system. There is a need to establish novel prognostic markers based on the molecular characterization of tumor cells. Evidence exists that sialyl LeX expression is correlated with an unfavorable outcome in colorectal cancer. The aim of this study was to establish a simple sialyl LeX staining score and to determine a potential correlation with the prognosis in a series of advanced colorectal carcinoma patients. Methods In order to implement routine use of sialyl LeX immunohistology, we established a new, easily reproducible score and defined a cutoff which discriminated groups with better or worse outcome, respectively. We then correlated sialyl LeX expression of 215 UICC stage III and IV patients with disease-free and cancer-related survival. Results A five-stage score could be established based on automated immunohistochemical stainings. Using a