Malpica, A; Wong, K-K
Molecular studies in ovarian serous borderline tumors (OSBTs) have been used to understand different aspects of this neoplasm. (i) Pathogenesis, Kras and Braf mutations represent very early events in the tumorigenesis of OSBT as both are detected in serous cystadenomas associated with OSBTs. In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations. In OSBTs, Kras mutations range from 17% to 39.5%, while Braf mutations range from 23% to 48%. The former is comparable with the range of Kras mutations in ovarian low-grade serous carcinomas (OLGSCa), 19%-54.5%. In contrast, Braf mutations in OLGSCa range from 0% to 33%. Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa. OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes. In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations. (ii) The relationship between OSBTs and the extraovarian disease, a monoclonal versus mutifocal origin? This is still matter of debate as studies using different techniques have failed to settle this controversy. (iii) Biological behavior, Braf mutations appear to have a protective role against the progression of OSBT to OLGSCa, while Kras mutations are commonly seen in cases of OSBT that recurred as LGSCa. Nevertheless, LGSCa as a recurrence of an OSBT can originate from OSBTs with or without detectable Kras mutations. Also, it appears to be an association between Kras G12v mutation and a more aggressive phenotype of OSBT that recurred as LGSCa. (iv) Actionable targets, currently there are limited data. It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras.
Imamura, Hiroko; Ohishi, Yoshihiro; Aman, Murasaki; Shida, Kaai; Shinozaki, Tomoko; Yasutake, Nobuko; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao
Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.
Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D
The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.
Cruz-Galarza, Daniel; Pérez-Rodríguez, Omar; Laboy-Torres, Joaquín; Gutiérrez-Rivera, Silvia
Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.
Krasevic, Maja; Stankovic, Teodora; Petrovic, Oleg; Smiljan-Severinski, Neda
Background Compared with their ovarian counterparts, serous borderline tumors of the fallopian tube are uncommon, with limited experience about their clinical behaviour. We present a case of serous borderline tumor of the fallopian tube with unusual presentation and summarise all the published cases to date. Case presentation A case of serous borderline tumor of the fallopian tube in a 34-year old patient is presented, incidentally found during routine gynecologic examination. At laparoscopy the tumor was unusualy presented as hematosalpinx and was treated by salpingectomy. Cell-cycle analysis of the tumor tissue revealed a diploid DNA content and a low S-phase fraction. There was no evidence of the disease during the follow-up period of 4.6 years. Conclusion The current case and review of the literature suggest salpingectomy as the optimal treatment for patients with serous borderline tumor of the fallopian tube. PMID:16212662
Srinivasamurthy, Banushree C; Kulandai Velu, Ambedkar Raj; Krishnan, Nagarajan; Patil, Anand Shankar Rao
Serous borderline tumors (SBT) are defined by the World Health Organization (WHO) as serous neoplasms that show epithelial proliferation greater than that seen in serous cystadenomas, as evidenced by cellular stratification, cytologic atypicality, and epithelial tufting, but which exhibit no evidence of "destructive stromal" invasion and can show extra-ovarian implants. Characterization of invasive peritoneal implants from patients with noninvasive serous ovarian tumors has important prognostic and treatment implications. Peritoneal implants have been classified as either noninvasive or invasive based on their histopathologic appearance. Three criteria were applied for the diagnosis of "invasive" implants: Invasion of underlying normal tissue, micropapillary architecture, and solid epithelial nests surrounded by clefts. We encountered two cases of unilateral ovarian serous borderline tumors with non-invasive peritoneal implants in a 43-year-old female, and invasive peritoneal implants in 76-year-old female.
Stephens, Daniel; Pillai, Srikumar; Cham, Elaine; Arensman, Robert; Chou, Pauline
We describe a case of a 3-year-old girl with Klippel-Trenaunay syndrome who presented with an enlarging abdominal mass caused by a serous borderline tumor of the fallopian tube. This case is notable for the rarity of this neoplasm in a premenarchal patient as well as the association with this syndrome. We briefly review these entities and the significance of malignancy in Klippel-Trenaunay syndrome. Copyright © 2010 Elsevier Inc. All rights reserved.
Aktaş, Işıl Yildiz; Buğdayci, Meral; Usubütün, Alp
According to the widely accepted pathway, a serous borderline tumor becomes invasive either by progressing into a noninvasive micropapillary tumor or directly through microinvasion. Our objective was to investigate the role of serous borderline tumors and their accompanying extraovarian lesions in pathogenesis of serous ovarian cancer using immunohistochemistry as a tool. An immunohistochemical panel of p16, p53, CD24, EpCAM and calretinin was applied to cutting edge matrix assembly-like tissue arrays of 46 cases consisting of typical, focal micropapillary, micropapillary, microinvasive, cystadenoma, and low-grade carcinoma cases. These tissue arrays are better choices than conventional tissue arrays to examine thin walled and heterogenous neoplasia like serous borderline tumors as they facilitate the analysis with linear sections rather than a core. For two tumor supressor gene markers; no diffuse and strong expression of p53, and strong and patchy/heterogenous expression of p16 were detected in all cases. Focal and strong calretinin expression was detected in micropapillary tumors while expression of EpCAM was lost in the same areas. Strong cytoplasmic CD24 expression was detected in cases with peritoneal implants, favoring the theory that change of expression localization of cell adhesion molecules is in accordance with phenotypical changes and tumor progresssion. Furthermore, circumfrential membranous and cytoplasmic expression of CD24 and EpCAM was detected in neoplastic cells in lymph nodes and microinvasion areas. Our results show that different levels of serous ovarian tumor progression are accompanied by changes in the immunohistochemical expression pattern of EpCAM, CD24, and calretinin.
Emmanuel, Catherine; Chiew, Yoke-Eng; George, Joshy; Etemadmoghadam, Dariush; Anglesio, Michael S; Sharma, Raghwa; Russell, Peter; Kennedy, Catherine; Fereday, Sian; Hung, Jillian; Galletta, Laura; Hogg, Russell; Wain, Gerard V; Brand, Alison; Balleine, Rosemary; MacConaill, Laura; Palescandolo, Emanuele; Hunter, Sally M; Campbell, Ian; Dobrovic, Alexander; Wong, Stephen Q; Do, Hongdo; Clarke, Christine L; Harnett, Paul R; Bowtell, David D L; deFazio, Anna
Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. ©2014 American Association for Cancer Research.
Danilewicz, Marian; Suzin, Jacek; Wagrowska-Danilewicz, Malgorzata; Spych, Michal; Tylinski, Wieslaw; Topczewska-Tylinska, Katarzyna; Piekarski, Janusz; Kazmierczak-Lukaszewicz, Sylwia; Cialkowska-Rysz, Aleksandra
Introduction There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors. Material and methods The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors. Results sAgNOR in adenomas, borderline tumors and cancers was in the following ranges: (0.73 ±0.23) × 106, (0.81 ±0.18) × 106 and (0.96 ±0.33) × 106 [AgNOR/cm2] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 106 (G1), (0.98 ±0.37) × 106 (G2) and (0.82 ±0.24) × 106 (G3) [AgNOR/cm2] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis. Conclusions sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven. PMID:23515230
Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors
Background In many tumors including ovarian cancer, cell proliferation and apoptosis are important in pathogenesis and there are many alterations in most of the genes related to the cell cycle. This study was designed to evaluate immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, and bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in typing of benign, borderline, and malignant serous and mucinous ovarian tumors. Methods Total of 68 ovarian tumors, 25 benign [13 (19.1%) serous and12 (17.6%) mucinous], 16 borderline [9 (13.2%) serous and 7(10.3%) mucinous], and 27 malignant ovarian tumors [24 (35.3%) serous and 3 (4.4%) mucinous tumors] were included in the study. Immunohistochemical expression of p53, p21, bax, bcl–2, telomerase, c-kit, and metallothionein were evaluated. Results When all 68 cases were evaluated as benign, borderline, and malignant ovarian tumors without considering histopathological subtypes, the p53, p21, bax and metallothionein showed significantly higher staining scores in the borderline and malignant ones (p < 0.05). After evaluation of all 68 cases, the serous tumors showed significantly higher staining scores of p53, p21, c-kit, and metallothionein compared to the mucinous ones (p < 0.05). For differentiation of benign and borderline and malignant tumors combined, p53 was not used because all benign tumors has no staining, and p21, bax, and metallothionein was determined the significant predictors for borderline and malignant tumors combined (p < 0.05). For differentiation of borderline and malignant tumors, only p53 was determined the significant predictor for malignant tumors (p < 0.05). Conclusions In conclusion, p53, p21, bax, c-kit, and metallothionein may be helpful for the typing of ovarian tumors as benign, borderline and malignant or serous and mucinous. p53, p21, bax, c-kit, and metallothionein may have different roles in the pathogenesis of ovarian tumor types. p53 and
Chisté, Marcela; Alexis, John; Recine, Monica
Insulin-like growth factor II mRNA-binding protein (IMP3) is an oncofetal protein involved in embryogenesis, which is expressed in a variety of malignant neoplasms. It is rarely expressed in normal adult tissue and benign tumors. The aim of this study was to evaluate the expression of IMP3 in benign and malignant serous tumors of the ovary. Seventy-nine ovarian tumors were examined for IMP3 expression by immunohistochemical analysis, comprising 16 benign serous tumors, 19 borderline serous tumors, and 44 serous carcinomas. Positive staining was defined as brown staining in the cytoplasm. Negative staining was defined as absent staining or staining of <5% of tumor cells. The intensity of staining (weak, moderate, and strong) and percentage (0% to 100%) of neoplastic cells staining positive for cytoplasmic IMP3 staining were recorded in each case. Moderate to strong cytoplasmic staining for IMP3 was observed in 30 of 44 (68%) serous carcinomas of the ovary; in contrast, <5% of the borderline and benign serous tumors expressed IMP3 ranging from weak to strong cytoplasmic staining. Statistically, the difference in IMP3 expression between these groups of tumors was highly significant (P<0.0001). Our findings demonstrate moderate to strong expression of IMP3 in the majority of ovarian serous carcinomas as compared with benign/borderline serous tumors, which demonstrated weak to strong expression in a small minority (<5%) of the tumors. Thus, IMP3 may be a useful adjunctive tool in the pathologic evaluation of ovarian serous tumors.
Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor
Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.
Ho, Ronnie S L; Chan, Godfrey C F; Ha, Shau Yin; Ip, Philip P C
Endometriosis in infancy is most unusual, and associated tumors in this age group are exceptionally rare. We report a case of a serous borderline tumor and endometrial stromal sarcoma arising in an ovarian endometriotic cyst. The patient was an infant of 18 months of age who presented with an incidental abdominal mass. The serum sex hormones were at prepubertal levels. There was no evidence of precocious puberty or any obvious genital anomaly. Intraoperative findings included a solitary solid and multicystic right ovarian mass without evidence of any extraovarian disease. On microscopic examination, the tumor was composed of an intimate mixture of florid papillary and stromal cell proliferation in the wall of an endometriotic cyst. The papillae showed hierarchical branching and had hyalinized and edematous cores with scattered psammoma bodies. The epithelial cells were mildly atypical and mitotically inactive. The underlying endometrial stromal cells were arranged in irregular tongues that permeated the thickened fibrous cyst wall. They were mitotically active and immunoreactive for CD10. There was no evidence of any primitive germ cell tumor. The patient received no adjuvant treatment and had an uneventful postoperative follow-up period of 30 months. To the best of our knowledge, endometriosis associated with this most unusual combination of ovarian tumors has never been reported in an infant.
Demirag, Guzin Gonullu; Kefeli, Mehmet; Kemal, Yasemin; Yucel, Idris
The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity.
Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K
Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright Â© 2017 Elsevier Inc. All rights reserved.
Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo
Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.
Wang, Min; Ma, Haifen
It has been suggested that Paired box gene (PAX)2 is activated by estradiol via estrogen receptor (ER)α in breast and endometrial cancer. The expression of PAX2 was restricted to ovarian serous tumors and only one case was positive in borderline mucinous tumor in our previous study. In the present study, immunohistochemistry was performed to assess the expression of ERα in 58 cases of ovarian serous tumors, including 30 serous cystadenomas, 16 borderline serous cystadenomas, 12 serous carcinomas and 67 cases of ovarian mucinous tumors, including 29 mucinous cystadenoma, 23 borderline mucinous cystadenoma and 15 mucinous carcinoma, which were the same specimens with detection of PAX2 expression. The results demonstrated that ERα was expressed in 10% (3/30) of serous cystadenomas, 62.5% (10/16) borderline serous cystadenomas and 66.7% (8/12) serous carcinomas. The expression of ERα in borderline serous cystadenomas and serous carcinomas were significantly higher compared with that in serous cystadenomas (P<0.01). ERα was detected in 3.4% (1/29) mucinous cystadenoma, 26.1% (6/23) borderline mucinous cystadenoma and only 6.7% (1/15) mucinous carcinoma. Furthermore, a scatter plot of the expression of PAX2 and ERα revealed a linear correlation between them in ovarian serous tumors (P<0.0001). With few positive results, no correlation was determined in ovarian mucinous tumors. It was demonstrated that PAX2 is associated with ERα in ovarian serous tumors, and this may become a potential theory basis for targeted therapy for ovarian serous tumors. Further research is required to determine how PAX2 and ERα work together, and the role of targeted therapy in ovarian serous tumors.
Laury, Anna R; Hornick, Jason L; Perets, Ruth; Krane, Jeffrey F; Corson, Joseph; Drapkin, Ronny; Hirsch, Michelle S
Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Müllerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P<0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker
Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid
Objective Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Methods Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. Results 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. Conclusions These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast
Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid
Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and
Luchian, Alina-Mihaela; Pricop, M
Ovarian borderline tumors are rare, their good prognosis depending on their stage at the time of diagnosis, and the presence of invasive implants. There is little information on tumor type identified intra-surgically, as well as on the most favorable treatment in borderline ovarian tumors. To determine the criteria of identification and presurgery and intra-surgery differentiation of the ovarian borderline tumors from the invasive carcinoma and benign ovarian tumors. This study included 54 patients with TPMS (ovarian borderline tumors) surgically treated in the past 22 years (January 1988-December 2009) at the 4th Gynecological Clinic of the lasi "Gr. T. Popa" University of Medicine and Pharmacy. In this interval 1,107 ovarian tumors: 575 benign, 478 malignant, and 54 TPMS (4.87%) were recorded. The age of the patients with borderline tumors ranged between 20 and 78 years, mean age 46 years, and the histological types were: mucinous (27 cases), serous (18 cases), mixed (8 cases), and Brenner tumor (1 case). We have analyzed the distribution of these cases according to the time when surgical treatment was performed. The frequency of borderline ovarian tumors in our study is 4.87%, lower than in the literature. We believe that this low percentage in our study is due to missing the microscopic data in some macroscopic benign tumors. By this research we aimed at elaborating a therapeutic strategy for each case using with discernment the modern treatment (surgery, chemotherapy, radiotherapy), as well as new chemical drugs with the goal of obtaining better results and longer survival. There are no tumor markers which could predict the progression of a borderline ovarian tumor to invasive tumors, but the invasive course is only 0.7%.
Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M
Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur more frequently.
Incidence of serous tubal intraepithelial carcinoma (STIC) by algorithm classification in serous ovarian tumor associated with PAX8 expression in tubal epithelia: a study of single institution in Japan.
Munakata, Satoru; Yamamoto, Toshiya
Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (P<0.05). Serous tubal intraepithelial carcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (P<0.05). Patients with SCP were significantly older (P<0.0001). Our observations were concordant with the hypothesis of serous ovarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer.
Gueli Alletti, Salvatore; Rossitto, Cristiano; Perrone, Emanuele; Cianci, Stefano; De Blasis, Ilaria; Fagotti, Anna; Scambia, Giovanni
To investigate the safety and technical feasibility of needleoscopic fertility-sparing staging of borderline ovarian tumors. Video article and review of the literature (Canadian Task Force classification Level III). This 29-year-old woman had a right ovarian cyst suspicious for borderline ovarian tumor on preoperative magnetic resonance imaging and ultrasound showing the presence of a right unilocular ovarian cyst with a papillary projection. Informed consent for abdominal or laparoscopic approach was obtained from the patient in accordance with the local legislation. The patient also provided informed consent to use images and videos of the procedure. Institutional Review Board approval was not required for this kind of procedure. Treatment involved conservative staging with right ovarian cystectomy, peritoneal biopsies, infracolic omental biopsy, and peritoneal cytology. Instrumentation included two 2.4-mm needleoscopic instruments. The total operative time was 62 minutes, and estimated blood loss was <10 mL. No intraoperative complications were recorded. At the end of the surgical procedure, the outer diameter of the incision was increased by only up to 3 mm. The patient was discharged the day after the procedure. Histopathological analysis confirmed a serous borderline ovarian tumor. A 30 days postoperative follow-up, a satisfactory cosmetic result was reported by both the patient (score of 10 of out of a possible 10) and the surgeon (10 of 10). To the best of our knowledge, there are no previously published reports of needleoscopic treatment of borderline ovarian tumor, which represents a great challenge for ultra-minimally invasive approaches [1-3]. Based on our initial experience, the needleoscopic instruments could prove to be a beneficial tool in adnexal benign or borderline disease. At present, only a hybrid operative setting should be considered to overcome the lack of bipolar energy [4-6]. Further studies are needed to define the benefits
Ushijima, Kimio; Kawano, Kouichiro; Tsuda, Naotake; Nishio, Shin; Terada, Atsumu; Kato, Hiroyuki; Tasaki, Kazuto; Matsukuma, Ken
Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.
Kalapotharakos, Grigorios; Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer
We conducted an evaluation of incidence and survival of women with borderline ovarian tumors in Sweden. All women diagnosed with borderline ovarian tumor in the Swedish Cancer Register 1960-2007 (n = 6252) combined with follow up in the Swedish Death Registry to 1 July 2009 were included. Estimation of age-standardized relative survival rate according to time periods for diagnosis. The incidence of borderline ovarian tumors increased during the study period, with a steep increase during the 1980s. The age standardized 5-year relative survival including all borderline tumors diagnosed 2000-07 was 97% (95% CI 92-99%). In women aged ≤64 years, the 10-year relative survival related to age at diagnosis of borderline tumors ranged from 95 to 98% and was 89% in women aged 65-74 years. In a multivariable analysis including age and decade of diagnosis relative survival for every decade increased. The 10-year relative survival in women with mucinous and serous borderline tumors did not differ significantly (p = 0.121). Results of the present study are reassuring about long-term survival in women with borderline ovarian tumors. The age-standardized relative survival rate increased across time periods for diagnosis. There was no difference in long-term survival between mucinous and serous borderline ovarian tumors. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.
Khalid, Saifullah; Jamal, Faisal; Rafat, Dalia; Ahmed, Murad; Narayanasamy, Sabarish; Obaid, Amber; Shadan, Mariam
Hydatid disease (HD) is a commonly occurring zoonotic disease caused by tapeworms of the genus Echinococcus. It is endemic in many parts of the world and can involve almost any organ of the body. Although HD of the liver and lungs is quite common, ovarian involvement is rare. We present a case of a 24-year-old female patient who was diagnosed with multifocal hydatidosis involving the liver and bilateral ovaries on imaging. Postoperative histopathology confirmed the hydatid disease in the liver and one ovary. However, the cystic lesion in the other ovary turned out to be a borderline serous cystadenoma. This case highlights the limitation of imaging in differentiating between simple hydatid cysts and serous cystadenomas of the ovaries. Another point we learnt is that even in the presence of multifocal hydatidosis in endemic regions, serous cystadenoma needs to be considered in imaging differential diagnosis.
Wong, Kwong-Kwok; Gershenson, David
The role of serous tumors of low malignant potential (LMP) in the development of invasive epithelial cancer of the ovary is debatable. This review summarizes the current clinical, genetic, and genomic evidence for the existence of a continuum comprising both LMP serous tumors and low-grade serous ovarian carcinomas. PMID:18057521
Hauptmann, Steffen; Friedrich, Katrin; Redline, Raymond; Avril, Stefanie
Borderline ovarian tumors (BOT) are uncommon but not rare epithelial ovarian neoplasms, intermediate between benign and malignant categories. Since BOT were first identified >40 years ago, they have inspired controversies disproportionate to their incidence. This review discusses diagnostic criteria for the histologic subtypes of BOT, highlighting areas of diagnostic challenges, ongoing controversies, and changes in terminology implemented by the recent 2014 WHO Classification of Tumours of the Female Genital Organs. Emerging knowledge supports the notion that subtypes of borderline ovarian tumors comprise distinct biologic, pathogenetic, and molecular entities, precluding a single unifying concept for BOT. Serous borderline tumors (SBT) share molecular and genetic alterations with low-grade serous carcinomas and can present at higher stages with peritoneal implants and/or lymph node involvement, which validates their borderline malignant potential. All other (non-serous) subtypes of BOT commonly present at stage I confined to the ovary(ies) and are associated with overall survival approaching that of the general population. An important change in the WHO 2014 classification is the new terminology of non-invasive implants associated with SBT, as any invasive foci (previously called "invasive implants") are now in line with their biological behavior considered peritoneal low-grade serous carcinoma (LGSC). The controversy regarding the terminology of non-serous borderline tumors, called by some pathologists "atypical proliferative tumor" in view of their largely benign behavior, has not been resolved. The concepts of intraepithelial carcinoma and microinvasion may evolve in further studies, as their presence appears to have no prognostic impact and is subject to considerable inter-observer variability.
Ferreira, Patrícia Andréia Rodrigues; Sallum, Luis Felipe Trincas Assad; Sarian, Luis Otávio; Andrade, Liliana A Lucci De Angelo; Derchain, Sophie
To compare the clinical-pathological features of women with serous and non-serous ovarian tumors and to identify the factors associated with survival. In this reconstructed cohort study, 152 women with ovarian carcinoma, who attended medical consultations between 1993 and 2008 and who were followed-up until 2010 were included. The histological type was clearly established for all women: 81 serous carcinomas and 71 non-serous tumors (17 endometrioid, 44 mucinous and 10 clear cell carcinomas). The crude and adjusted odds ratios (OR), with the respective 95% confidence intervals (95%CI), were calculated for the clinical and pathological features, comparing serous and non-serous histological types. The Hazard Ratios (HR) with 95%CI was calculated for overall survival, considering the clinical and pathological features. Comparison of serous to non-serous tumor types by univariate analysis revealed that serous tumors were more frequently found in postmenopausal women, and were predominantly high histological grade (G2 and G3), advanced stage, with CA125>250 U/mL, and with positive peritoneal cytology. After multivariate regression, the only association remaining was that of high histological grade with serous tumors (adjusted OR 15.1; 95%CI 2.9-77.9). We observed 58 deaths from the disease. There was no difference in overall survival between women with serous carcinoma and women with non-serous carcinoma (HR 0.4; 95%CI 0.1 - 1.1). It was observed that women aged 50 years or less (HR 0.4; 95%CI 0.1-0.9) and those who were in menacne (HR 0.3; 95%CI 0.1-0.9) had a longer survival compared respectively to those above 50 years of age and menopaused. High histological grade (G2 and G3) (p<0.01), stages II-IV (p<0.008) and positive cytology (p<0.001) were significantly associated with worse prognosis. CA125 and the presence of ascites did not correlate with survival. Survival was poor when the disease was diagnosed in stages II to IV and compared to stage I (log-rank p<0
El Din, Amina A Gamal; Badawi, Manal A; Aal, Shereen E Abdel; Ibrahim, Nihad A; Morsy, Fatma A; Shaffie, Nermeen M
Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours.
Kuo, Kuan-Ting; Guan, Bin; Feng, Yuanjian; Mao, Tsui-Lien; Chen, Xu; Jinawath, Natini; Wang, Yue; Kurman, Robert J.; Shih, Ie-Ming; Wang, Tian-Li
Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, was thought to develop from two distinct molecular pathways. High-grade (HG) serous carcinomas contain frequent TP53 mutations while low-grade (LG) carcinomas arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2 pathway. However, the molecular alterations involved in the progression from SBT to LG carcinoma remain largely unknown. As well, the extent of deletion of tumor suppressors in ovarian serous carcinomas has not been well-studied. To further address these two issues, we assessed DNA copy number changes among affinity-purified tumor cells from 37 ovarian serous neoplasms including SBT, LG and HG tumors using high density 250K SNP arrays. Chromosomal instability index as measured by changes in DNA copy number was significantly higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common in LG serous carcinomas but was rarely seen in SBT. This region contains several candidate tumor suppressors including miR-34a. In contrast, in HG serous carcinomas, significant numbers of amplifications and deletions including homozygous deletions were identified. Among homozygous deletions, loci containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in 10.6%, 6.4%, 6.4% and 4.3%, respectively, in independent 47 affinity-purified HG serous carcinomas. Except the CDKN2A/B region, these homozygous deletions were not present in either SBT or LG tumors. Our study provides a genome-wide homozygous deletion profiles in HG serous carcinomas, serving as a molecular foundation to study tumor suppressors in ovarian cancer. PMID:19383911
Grimaldi, Luciano; Danzi, Michele; Reggio, Stefano; Pannullo, Mario; Danzi, Roberta; Lauria, Rossella
Psammocarcinoma is a rare variant of serous carcinoma arising either from ovary or peritoneum, characterized by massive psammoma body formation, low-grade of cytologic differentiation and invasiveness. Its clinical behavior is similar to the serous borderline tumors, whose prognosis is significantly better compared to invasive forms, with a 5-year survival in stage I greater than 95%. A typical feature of borderline ovary tumors is the presence, in more than 30% of cases, of borderline peritoneal implants similar to primary ovarian cancer or of invasive forms. We report a case of a 44-years-old woman who referred to our clinic for mesosigmoid mass , accidentally discovered by ultrasonography. Sigmoidectomy with fertility sparing surgery was performed in september 2010. The mass was hystologically characterized by many psammoma bodies and low grade cytological features with diagnosis of psammocarcinoma of mesosigma. One year after the primary surgery, the patient showed with left adnexial mass; optimal debulking surgery was performed including omentectomy, total abdominal hysterectomy, bilateral adnexectomy and appendicectomy. The patient did not receive any adjuvant chemotherapy and to date she is alive and with no evidence of disease. The conclusion is that psammocarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma, the mainstay of treatment is surgical debulking , with fertility sparing surgery as possible option in young patients with ovaries macroscopically free of disease.
Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna; Andersen, Klaus K; Kjaer, Susanne K
Some studies suggest that pelvic inflammatory disease (PID) is a potential risk factor for ovarian cancer. However, only few studies have investigated the association between PID and risk of borderline ovarian tumors. We conducted a population-based cohort study to investigate the association between PID and risk of borderline ovarian tumors. Using various nationwide Danish registries we identified all women in Denmark during 1978-2012, who were born during 1940-1970 (n=1,318,925). Of these, 81,263 women were diagnosed with PID in the study period, and 2736 women had a borderline ovarian tumor (1290 serous and 1344 mucinous). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and risk of borderline tumors were estimated using Cox regression models with adjustment for potential confounders. A history of PID was associated with an increased risk of borderline ovarian tumors (HR=1.39; 95% CI: 1.19-1.61). However, histotype-specific analyses revealed significant variation in risk as PID was only associated with an increased risk of serous borderline tumors (HR=1.85; 95% CI: 1.52-2.24), but not with mucinous borderline tumors (HR=1.06; 95% CI: 0.83-1.35). PID is associated with an increased risk of serous borderline tumors. Further research on the potential underlying biological mechanisms and on the identification of the subset of women with PID who are at increased risk of serous borderline tumors is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.
Park, Jee Soo; Choi, Soo Beom; Kim, Hee Jung; Cho, Nam Hoon; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji; Chung, Jai Won; Kim, Deok Won
Serous borderline ovarian tumors (SBOTs) are a subtype of serous ovarian carcinoma with atypical proliferation. Frozen-section diagnosis has been used as an intraoperative diagnosis tool in supporting the fertility-sparing surgery by diagnosing SBOTs with accuracy of 48% to 79%. Using DNA microarray technology, we designed multicategory classification models to support frozen-section diagnosis within 30 minutes. We systematically evaluated 6 machine learning algorithms and 3 feature selection methods using 5-fold cross-validation and a grid search on microarray data obtained from the National Center for Biotechnology Information. To validate the models and selected biomarkers, expression profiles were analyzed in tissue samples obtained from the Yonsei University College of Medicine. The best accuracy of the optimal machine learning model was 97.3%. In addition, 5 features, including the expression of the putative biomarkers SNTN and AOX1, were selected to differentiate between normal, SBOT, and serous ovarian carcinoma groups. Different expression levels of SNTN and AOX1 were validated by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. A multinomial logistic regression model using SNTN and AOX1 alone was used to construct a simple-to-use equation that gave a diagnostic test accuracy of 91.9%. We identified 2 biomarkers, SNTN and AOX1, that are likely involved in the pathogenesis and progression of ovarian tumors. An accurate diagnosis of ovarian tumor subclasses by application of the equation in conjunction with expression analysis of SNTN and AOX1 would offer a new accurate diagnosis tool in conjunction with frozen-section diagnosis within 30 minutes.
Chambers, J. T.
Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment. PMID:2556863
Park, Jee Soo; Choi, Soo Beom; Chung, Jai Won; Kim, Sung Woo; Kim, Deok Won
Ovarian cancer, the most fatal of reproductive cancers, is the fifth leading cause of death in women in the United States. Serous borderline ovarian tumors (SBOTs) are considered to be earlier or less malignant forms of serous ovarian carcinomas (SOCs). SBOTs are asymptomatic and progression to advanced stages is common. Using DNA microarray technology, we designed multicategory classification models to discriminate ovarian cancer subclasses. To develop multicategory classification models with optimal parameters and features, we systematically evaluated three machine learning algorithms and three feature selection methods using five-fold cross validation and a grid search. The study included 22 subjects with normal ovarian surface epithelial cells, 12 with SBOTs, and 79 with SOCs according to microarray data with 54,675 probe sets obtained from the National Center for Biotechnology Information gene expression omnibus repository. Application of the optimal model of support vector machines one-versus-rest with signal-to-noise as a feature selection method gave an accuracy of 97.3%, relative classifier information of 0.916, and a kappa index of 0.941. In addition, 5 features, including the expression of putative biomarkers SNTN and AOX1, were selected to differentiate between normal, SBOT, and SOC groups. An accurate diagnosis of ovarian tumor subclasses by application of multicategory machine learning would be cost-effective and simple to perform, and would ensure more effective subclass-targeted therapy.
Luchian, Alina-Mihaela; Pricop, M
There is limited information on borderline ovarian tumor detected intra-surgically and its most favorable treatment in relation with global radiation and climate changes. To study the pre-surgery and intra-surgery differentiation criteria of borderline ovarian tumors from invasive carcinoma, and to make a very complex analysis of the frequency, distribution, and variation in time of global radiation, temperature, and precipitation in North-East Romania. The 54 patients (age range 20-78 years, mean age 46 years) included in this study had borderline ovarian tumors surgically treated during the last 22 years (January 1988 - December 2009) at the 4th Gynecological Clinic at Iaşi, and representing 4.87% of the total 1107 ovarian tumors detected and treated during this interval. The histological types were: serous (18 cases), mucinous (27 cases), mixed (8 cases), and Brenner tumor (1 case). In order to analyze the impact of climate changes on borderline ovarian tumors a thorough study on the frequency of global radiation in relation with climate changes based on data recorded in the last 55 years was also carried out. The distribution of these cases depending on when surgery was performed was analyzed. In our study the frequency of ovarian borderline tumors (4.87%) is lower than in similar reports in the literature being due, in our opinion, to the influence of global radiation in relation with climate changes. In our study global radiation is probably responsible for a progression to invasive carcinoma in 0.7% of the borderline ovarian tumors.
Harlow, B L; Weiss, N S
The authors interviewed 116 female residents of western Washington State with serous and mucinous borderline ovarian tumors diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders. A sample of 158 control women from the same counties were identified through random digit dialing and were interviewed as well. Neither the perineal application of baby powder nor the perineal application of cornstarch was associated with an appreciably altered risk of borderline ovarian tumors. However, women who used deodorizing powders alone or in combination with other talc-containing powders had 2.8 times the risk (95% confidence interval 1.1-11.7) of women who had not had perineal exposure to powder. These results suggest that future studies of ovarian tumors in relation to the application of talc-containing powders should consider ascertaining the specific type(s) of powder used.
el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.
BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284
Hacker, Kari E; Uppal, Shitanshu; Johnston, Carolyn
Borderline ovarian tumors (BOTs) are less common than epithelial ovarian cancers (EOCs). Low-grade EOCs (LG-EOCs) occur even less frequently than BOTs. After primary therapy, recurrence rates of BOTs and LG-EOCs are significantly lower and the stage-adjusted survival is higher than for high-grade EOCs. Thus, determining the best management in terms of traditional ovarian cancer staging and debulking procedures is more challenging and has been recently brought to question. This article reviews the particulars of BOTs and LG-EOCs, their similarities and differences, and how they are best managed and treated, and emphasizes the major role of surgery and the controversial role of chemotherapy. Because these tumors disproportionately affect younger women, this review addresses ovarian preservation in circumstances when fertility or hormonal preservation is desired. Copyright © 2016 by the National Comprehensive Cancer Network.
Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.
Background Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer. Methods In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes. Results The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas
Sallum, Luis Felipe; Sarian, Luis Otavio; Lucci De Angelo Andrade, Liliana; Vassallo, José; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Ferreira, Patrícia Andréia; Derchain, Sophie
To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression. We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry. Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01). Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression.
Sallum, Luis Felipe; Sarian, Luis Otavio; Lucci De Angelo Andrade, Liliana; Vassallo, José; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Ferreira, Patrícia Andréia
Objective To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression. Methods We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry. Results Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01). Conclusion Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression. PMID:23653835
Buas, Matthew F.; Gu, Haiwei; Djukovic, Danijel; Zhu, Jiangjiang; Drescher, Charles W.; Urban, Nicole; Raftery, Daniel; Li, Christopher I.
OBJECTIVE Serous ovarian carcinoma (OC) represents a leading cause of cancer-related death among U.S. women. Non-invasive tools have recently emerged for discriminating benign from malignant ovarian masses, but evaluation remains ongoing, without widespread implementation. In the last decade, metabolomics has matured into a new avenue for cancer biomarker development. Here, we sought to identify novel plasma metabolite biomarkers to distinguish serous ovarian carcinoma and benign ovarian tumor. METHODS Using liquid chromatography-mass spectrometry, we conducted global and targeted metabolite profiling of plasma isolated at the time of surgery from 50 serous OC cases and 50 serous benign controls. RESULTS Global lipidomics analysis identified 34 metabolites (of 372 assessed) differing significantly (P<0.05) between cases and controls in both training and testing sets, with 17 candidates satisfying FDR q<0.05, and two reaching Bonferroni significance. Targeted profiling of ~150 aqueous metabolites identified a single amino acid, alanine, as differentially abundant (P<0.05). A multivariate classification model built using the top four lipid metabolites achieved an estimated AUC of 0.85 (SD=0.07) based on Monte Carlo cross validation. Evaluation of a hybrid model incorporating both CA125 and lipid metabolites was suggestive of increased classification accuracy (AUC=0.91, SD=0.05) relative to CA125 alone (AUC=0.87, SD=0.07), particularly at high fixed levels of sensitivity, without reaching significance. CONCLUSIONS Our results provide insight into metabolic changes potentially correlated with the presence of serous OC versus benign ovarian tumor and suggest that plasma metabolites may help differentiate these two conditions. PMID:26521694
Mun, Semih; Uysal, Fatma; Öztekin, Murat; Büyüktosun, Cem; Şehirali1, Salim; Başoğul, Ömer; Taner, Cüneyt E.
Aim of the study The purpose of the study was to evaluate patients with borderline ovarian tumors. Material and methods Clinical features, treatment and survival status of 100 patients with borderline ovarian tumors were retrospectively evaluated between 1998 and 2007. Results Patients’ mean age was 37.75 years (range: 15–72); 22 of them were postmenopausal. Histopathological diagnoses were serous, mucinous, endometrioid and clear cell in 54%, 41%, 2% and 3% of the patients, respectively; 70 patients had stage IA disease, 8 were at stage IB, 16 at stage IC, 2 at stage IIIA, 3 at stage IIIB and 1 at stage IIIC. Restaging laparotomies were performed on 19 patients; fertility-sparing surgery was performed on 52 patients; 2 patients received chemotherapy because of advanced-stage disease. All patients are currently alive. The 5-year disease-free survival rate for 71 cases was 100%. Conclusions Borderline ovarian tumors have excellent prognoses, and fertility-conserving surgery can be performed in young patients with early-stage disease. PMID:24596520
Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A
Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.
Kharma, Budiman; Baba, Tsukasa; Matsumura, Noriomi; Kang, Hyun Sook; Hamanishi, Junzo; Murakami, Ryusuke; McConechy, Melissa M; Leung, Samuel; Yamaguchi, Ken; Hosoe, Yuko; Yoshioka, Yumiko; Murphy, Susan K; Mandai, Masaki; Hunstman, David G; Konishi, Ikuo
Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease.
Quddus, M Ruhul; Rashid, Lanita; Sung, C James; Steinhoff, Margaret M; Cunxian Zhang; Lawrence, W Dwayne
The association of Ewing's sarcoma/peripheral neuroectodermal tumor and endometrioid type endometrial carcinoma has been reported relatively recently. We have recently identified Ewing's sarcoma/peripheral neuroectodermal tumor differentiation in uterine serous carcinomas and undertook this study to evaluate the frequency of both serous and endometrioid carcinomas expressing Ewing's sarcoma/peripheral neuroectodermal tumor differentiation. Seventy cases of uterine serous carcinoma were retrieved from the archival files and stained with antibodies to CD99. Positive and negative control slides were run with each staining batch. Perinuclear dot-like and/or membranous staining was regarded as positive. The frequency of Ewing's sarcoma/peripheral neuroectodermal tumor differentiation in 56 FIGO grade 3 endometrioid carcinomas was also determined and 7% uterine serous and 12.5% of FIGO grade 3 endometrioid endometrial carcinomas showed Ewing's sarcoma/peripheral neuroectodermal tumor differentiation. Given the worse prognosis associated with Ewing's sarcoma/peripheral neuroectodermal tumor differentiation, even in neoplasms already at high risk for recurrence and metastasis, a high index of suspicion for Ewing's sarcoma/peripheral neuroectodermal tumor should be maintained in high-grade uterine serous carcinomas.
Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A
Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434
El-Gendi, Saba; Abdelzaher, Eman; Mostafa, Mohamed Farouk; Sheasha, Ghada Abu
Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumors, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type I and type II tumors. We also aimed to test the prognostic significance of this expression and its relation to microvessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumors and statistically analyzed their association with clinicopathological variables and patients' outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumors. MVD increased significantly only among serous tumors. FGF18 and MVD correlated significantly (overall and among serous tumors only) and were significantly higher in type II than type I tumors. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type I tumors and might modulate angiogenesis among serous tumors. Our findings further augment the differences between type I and type II tumors. The combination of FIGO stage, ovarian carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.
Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin
Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.
Bürger, Tobias; Schildhaus, Hans-Ulrich; Inniger, Reinhard; Hansen, Joachim; Mayer, Peter; Schweyer, Stefan; Radzun, Heinz Joachim; Ströbel, Philipp; Bremmer, Felix
Tumours of ovarian-epithelial type of the testis, including serous borderline tumours, represent very rare entities. They are identical to the surface epithelial tumours of the ovary and have been reported in patients from 14 to 68 years of age. We describe two cases of a 46- and a 39-year old man with incidental findings of intratesticular masses of the left respectively right testis. Under the assumption of a malignant testicular tumour the patients were subjected to inguinal orchiectomy. Histologically, the tumours were identical to their ovarian counterparts: They showed a cystic configuration with a fibrous wall and irregular papillary structures lined by partially multistratified columnar cells and areas of hobnail cells. Furthermore, there was mild cytological atypia with a proliferative activity of below 5% as proved by Ki67 staining; mitoses could not be detected. Immunohistochemically, the tumour cells displayed expression of pan-cytokeratin AE3, progesterone receptor, Wilms' tumour protein (WT1), and PAX8 (Paired box gene 8). Estrogen receptor was expressed in one case. Octamer-binding transcription factor-4 (OCT4), calretinin, thrombomodulin, and D2-40 were not expressed. Mutation testing of BRAF revealed a BRAF V600E mutation in one case, while testing for KRAS mutations proved to be negative in both. The BRAF mutated tumour showed strong cytosolic and membranous positivity for B-Raf also on immunohistochemical analysis. Comparative genomic hybridization of one case could not reveal any chromosomal aberrations.
Zikan, Michal; Dundr, Pavel; Cibula, David
Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type—easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients. PMID:23024155
Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G; Vang, Russell; Cope, Leslie; Junge, Jette; Kjaer, Susanne K; Kurman, Robert J; Shih, Ie-Ming
There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. PMID:24307542
Kim, Jo-Heon; Choi, Yoo Duk; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan; Park, Min Ho; Yoon, Jung Han
Mammary phyllodes tumors (PTs) are uncommon fibroepithelial neoplasms. On the basis of histologic criteria, PTs can be divided into benign, borderline, and malignant groups; however, the histologic distinction of PTs is often difficult and arbitrary. In breast cancer, promoter hypermethylation is a common phenomenon, but there are no data available concerning methylation status in PTs. The aim of this study was to assess whether the methylation profiles support the classification of PTs into three subgroups. A multiplex, nested, methylation-specific polymerase chain reaction approach was used to examine promoter methylation of five genes (GSTP1, HIN-1, RAR-beta, RASSF1A, and Twist) in 87 PTs (54 benign, 23 borderline, and 10 malignant). Immunohistochemical staining for GSTP1 was performed using tissue microarray blocks to determine whether GSTP1 promoter hypermethylation correlated with loss of GSTP1 expression. There was a trend of increasing methylation frequency with increasing grade of PTs. The methylation frequency of all genes and the mean number of methylated genes in borderline and malignant PTs were higher than those in benign PTs; however, there were no statistically significant differences between borderline and malignant PTs. GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.001). These results suggest that PTs segregate into only two groups on the basis of their methylation profiles: the benign group and the combined borderline/malignant group.
Buttarelli, Marianna; Martinelli, Enrica; Mascilini, Floriana; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Gallo, Daniela
Only recently low-grade serous carcinoma (LGSOC) of the ovary has been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSOC), with significant differences in pathogenesis and clinical and pathologic features. The present study aimed at evaluating whether the different natural histories and patterns of response to therapy demonstrated for LGSOC and HGSOC, along with a diverse genomic landscape, may also reside in the supporting tumor stroma, specifically in the state of differentiation and activation of tumor associated macrophages (TAMs). TAMs play complex roles in tumorigenesis since they are believed to possess both tumor rejecting (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we showed that, when compared to HGSOC (n = 55), LGSOC patients (n = 25) exhibited lower density of tumor-infiltrating CD68+ macrophage, along with an attenuated M2-skewed (CD163+) phenotype. Accordingly, assessment of intratumoral vascularization and of matrix metalloproteinase 9 expression (a key protein involved in tumor invasion and metastasis) revealed lower expression in LGSOC compared to HGSOC patients, in line with emerging evidence supporting a role for TAMs in all aspects of tumor initiation, growth, and development. In conclusion, results from the present study demonstrate that microenvironmental factors contribute greatly to determine clinical and pathological features that differentiate low and high grade serous ovarian carcinomas. This understanding may increase possibilities and opportunities to improve disease control and design new therapeutic strategies. PMID:27462782
Chen, M-Y; Jung, S-M; Ng, K-K; Chang, T-C
Papillary serous adenocarcinoma has been recognized as a highly malignant ovarian cancer and is also not uncommonly seen in primary lung cancer. Difficulty may exist in determining the origin of the primary tumor in women with synchronous pulmonary and ovarian tumors. We present a patient who was initially diagnosed and treated as stage IV papillary serous ovarian cancer with diffuse pulmonary metastases. Only transient symptomatic improvement was achieved after standard chemotherapy for ovarian cancer, and then she died of respiratory distress during treatment. Poor tumor response to chemotherapy prompted us to reevaluate the previous bronchoscopic biopsy, and immunohistochemical studies, which were cytokeratin (CK) 7 positive, CK20 negative, and thyroid transcription factor-1 (TTF-1)-positive, provided irrefutable evidences for the diagnosis of primary lung cancer. We suggest that in dealing with coexistence of ovarian and pulmonary tumors, immunohistochemical study by using CK7, CK20, and TTF-1 may be helpful in the differentiation of the primary origin.
Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun
Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.
Gao, Weiwei; Zhang, Qin; Wang, Yan; Wang, Jiandong; Zhang, Shu
Eph (Erythropoietin-producing human hepatocellular carcinoma cell) is the largest subfamily of receptor tyrosine kinases. Eph receptors and their ephrin ligands are involved in embryonic development and physiological processes. Aberrant expression of Eph/ephrin may contribute to a variety of diseases including cancer. EphB3 is a member of Eph receptors and has been found to play roles in carcinogenesis of some types of human cancer. But, its expression and clinical significance in ovarian serous carcinoma have not been well investigated and are unknown. In this study, a set of ovarian tissues including normal fallopian tube, serous borderline tumor, and serous carcinoma were subjected to immunohistochemistry using a specific polyclonal antibody for EphB3. The relationship between EphB3 expression and clinicopathological parameters was statistically analyzed. EphB3 was strongly expressed in all fallopian tube specimens (19/19, 100%). EphB3 was negatively or weekly expressed in 1 of 17 (5.8%) in borderline tumors and 26 of 50 (52.0%) in serous carcinomas, moderately expressed in 7 of 17 (41.2%) in borderline tumors and 14 of 50 (28%) in serous carcinomas, and strongly expressed in 9 17 (52.9%) in borderline tumors and 10 of 50 (20%) in serous carcinomas. EphB3 expression is significantly reduced in serous carcinomas compared with normal fallopian tubes and borderline tumors (p < 0.001). EphB3 expression is negatively associated with histological grade (p < 0.001, rs = -0.613) and FIGO stage (p = 0.001, rs = -0.464) of serous carcinomas. Our results show EphB3 protein lost in ovarian serous carcinoma and is associated with tumor grade and FIGO stage, which indicate EphB3 protein may play a role in carcinogenesis of ovarian serous carcinoma and may be used as a molecular marker for prognosis.
Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar
Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.
Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep
Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682
Poudel, R; Acharya, A; Pokhrel, S; Adhikari, S K
Mucinous cystic neoplasms are rare tumors of uncertain histogenesis. They arise from the ovaries, pancreas, and other intra-abdominal sites but more unusually from the mesentery. They can present with abdominal pain, distension, or a palpable mass but are commonly an incidental finding. We present a case of a 33-year-old female who presented with complain of pain abdomen for one-year duration. On Physical examination there was a palpable lump in right lumbar region extending to right iliac fossa. CT scan of abdomen and pelvis suggested the mass to be a Mesenteric Cyst. Enucleation of the cyst was done and histopathology report revealed Mucinous Cystic borderline tumor of the Mesentery.
Yong, W H; Southern, J F; Pins, M R; Warshaw, A L; Compton, C C; Lewandrowski, K B
Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors, some of which are malignant. Preoperative clinical and radiological parameters are unreliable and may result in incorrect diagnosis and inappropriate treatment. Cyst fluid analysis for cytology, viscosity, carcino-embryonic antigen, CA 72-4, and CA 15-3 will distinguish mucinous from nonmucinous lesions and usually help in determining malignancy. Currently, there is no reliable method to differentiate inflammatory pseudocysts from serous cystadenomas. This distinction is important because the treatment of these two lesions is different; pseudocysts are either observed or drained, whereas serous tumors are usually resected. The tumor marker NB/70K was measured in aspirated cyst fluid from 13 inflammatory pseudocysts and 11 serous cystadenomas by a commercial immunoassay. Leukocyte esterase was measured using Chemstrip SG urine test strips and amylase and lipase on a routine chemistry analyzer. The cyst fluid NB/70K concentration was significantly higher in pseudocysts (mean, 555 U/ml; range, 42-1,926 U/ml) than in serous cystadenomas (mean, 12 U/ml; range 0-130 U/ml) and this difference was significant (p < 0.0002). Leukocyte esterase was detected in 7 of 11 pseudocysts but was absent in 10 of 10 serous tumors (p = 0.002). Amylase and lipase values were generally higher in pseudocysts but these markers were unreliable due to marked outliers. Cyst fluid NB/70K and leukocyte esterase are promising markers to help differentiate pseudocysts from serous tumors on percutaneous aspirates. When combined with previously reported cyst fluid parameters (amylase, lipase, cytology, and amylase isoenzymes), these two cystic lesions can be reliably distinguished.
Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser
Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.
Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G.; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar
The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors. PMID:27665539
Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar
The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.
Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna; Bandera, Elisa V; Doherty, Jennifer A; Høgdall, Estrid; Webb, Penelope M; Jordan, Susan J; Rossing, Mary Anne; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Edwards, Robert P; Schildkraut, Joellen M; Berchuck, Andrew; Olson, Sara H; Kiemeney, Lambertus A; Massuger, Leon F A G; Narod, Steven A; Phelan, Catherine M; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H; Pearce, Celeste L; Risch, Harvey A; Jensen, Allan
Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kaku, Tsunehisa; Kato, Kiyoko; Oda, Yoshinao
"Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.
Lian, Chengying; Chen, Xiujuan; Ni, Yihua; Huang, Xiaochen; Lin, Yuan
To investigate the ability to conceive and the factors affecting chances of pregnancy among patients with borderline ovarian tumors (BOTs) treated with fertility-sparing surgery. A retrospective study included nulliparous patients aged 40years or younger who had undergone fertility-sparing surgery for BOTs between January 2005 and June 2012 at a center in Fuzhou, China. Identified patients were followed up by telephone or mail between March 15 and June 30, 2013. Patients who had already been pregnant and those who had not but had discontinued contraception for more than 1year were included in final analyses. Among 23 included patients, 17 (74%) had become pregnant within the mean follow-up period of 48.2months. The frequencies of previous infertility, sequelae of pelvic inflammatory disease, and endometriosis were all higher in the nonpregnant group than in the pregnant group (P≤0.021 for all). More women in the nonpregnant group that in the pregnant group had BOTs of stage II or worse, but the difference was nonsignificant (P=0.059). Fertility-sparing surgery in young patients with BOTs is associated with a good pregnancy rate. However, the tumor stage and coexisting infertility factors are important considerations in selecting the optimal surgical approach. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Gungor, Tayfun; Altinkaya, Sunduz Ozlem; Sirvan, Levent; Lafuente, Roberto Alvarez; Ceylaner, Serdar
Borderline ovarian tumors (BOTs) represent a heterogeneous group of ovarian epithelial neoplasms. Despite a favorable prognosis, 10-20% of BOTs exhibit progressively worsening clinic. Primary involvement of pelvic organs with echinococcus is very rare. Lymphoepithelioma-like gastric carcinoma is a rare neoplasm of the stomach. A 58-year-old woman referred with abdominal swelling and gastric complaints. Imaging studies revealed a huge cystic mass with multiple septations and solid component, another cystic mass with an appearance of cyst hydatid in the pelvis, and thickening of the small curvature of stomach. Gastroscopy revealed an ulcer with a suspicious malignant appearance, and histology of the endoscopic specimen showed severe chronic inflammation and lymphocytic infiltration. No other involvement of hydatid cyst was detected. In the exploration, there was a 25cm cystic lesion with solid components arising from right ovary, another 6cm cyst over the former, 7cm cystic lesion arising from left ovary, and 10cm mass near the small curvature of the stomach. Excision of the masses; total gastrectomy with esophagojejunal anastomosis; total abdominal hysterectomy; bilateral salpingo-oophorectomy; omentectomy; appendectomy; splenectomy; and pelvic, paraaortic, and coeliac lympadenectomy were performed. Final pathology revealed lymphoepithelioma-like gastric carcinoma, bilateral serous BOT, and hydatid cyst. Hydatid cyst should always be considered in the differential diagnosis of abdominopelvic masses in endemic regions of the world. Preoperative diagnosis of primary pelvic hydatid disease is difficult and awareness of its possibility is very important especially in patients residing in or coming from endemic areas. Copyright © 2011. Published by Elsevier B.V.
Le Gallo, Matthieu; O'Hara, Andrea J; Rudd, Meghan L; Urick, Mary Ellen; Hansen, Nancy F; O'Neil, Nigel J; Price, Jessica C; Zhang, Suiyuan; England, Bryant M; Godwin, Andrew K; Sgroi, Dennis C; Hieter, Philip; Mullikin, James C; Merino, Maria J; Bell, Daphne W
Endometrial cancer is the sixth most commonly diagnosed cancer in women worldwide, causing ~74,000 deaths annually. Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology. We used whole-exome sequencing to comprehensively search for somatic mutations within ~22,000 protein-encoding genes in 13 primary serous endometrial tumors. We subsequently resequenced 18 genes, which were mutated in more than 1 tumor and/or were components of an enriched functional grouping, from 40 additional serous tumors. We identified high frequencies of somatic mutations in CHD4 (17%), EP300 (8%), ARID1A (6%), TSPYL2 (6%), FBXW7 (29%), SPOP (8%), MAP3K4 (6%) and ABCC9 (6%). Overall, 36.5% of serous tumors had a mutated chromatin-remodeling gene, and 35% had a mutated ubiquitin ligase complex gene, implicating frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer.
Heinrich, J K R; Böttcher-Luiz, F; Andrade, L L A; Davidson, S; Bonds, L; Stephens, J; Varella-Garcia, M
The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45 borderline ovarian tumors (BOTs) and investigated the correlation of these biologic markers with histologic type, clinical stage, and outcome. The level of CA 125 protein was assessed using DAKO's M-11 clone antibody in immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy number per cell was investigated through fluorescence in situ hybridization (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors) and significantly associated with the serous histologic type. However, CA 125 expression did not associate with clinical stage or outcome. Protein overexpression or gene amplification of HER-2 was not found. However, abnormal FISH results were detected in 16% (seven out of 45 patients) of specimens comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal FISH results were found to be independent of CA 125 expression and histologic type whereas they positively associate with advanced clinical stage. Our data show that HER-2 is not altered in BOTs, and the presence of aneusomy for chromosome 17 and HER-2 may predict tumor progression.
Śniadecki, Marcin; Bianek-Bodzak, Agnieszka; Liro, Marcin; Szurowska, Edyta
Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning. PMID:28138412
Mitra, Anirban; Davis, David A.; Tomar, Sunil; Roy, Lynn; Gurler, Hilal; Xie, Jia; Lantvit, Daniel D.; Cardenas, Horacio; Fang, Fang; Liu, Yueying; Loughran, Elizabeth; Yang, Jing; Stack, M. Sharon; Emerson, Robert E; Cowden Dahl, Karen D.; Barbolina, Maria; Nephew, Kenneth P.; Matei, Daniela; Burdette, Joanna E.
Objective Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown. Methods To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119, UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression. Results Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic. Conclusions Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community. PMID:26050922
Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T.; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar
High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer. PMID:27172797
Cabral, Vinicius Duarte; Cerski, Marcelle Reesink; Sa Brito, Ivana Trindade; Kliemann, Lucia Maria
Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results. There are no reports on its expression in benign and borderline tumors. This study aims to determine p14, p16 and p53 expression frequencies in ovarian benign, borderline and malignant tumors and their associations with clinical parameters. A cross-sectional study utilizing immunohistochemistry was performed on paraffin-embedded ovarian epithelial tumor samples. Clinical data were collected from medical records. Fisher's exact test and the Bonferroni correction were performed for frequency associations. Survival comparisons utilized Kaplan-Meier and log rank testing. Associations were considered significant when p < 0.05. p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560). No associations were found between expression rates, disease-free survival times or clinical variables. Carcinoma subtypes showed no difference in expression. This is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate that p14 abnormalities occur later in carcinogenesis. p16 and p53 frequencies increase from benign to borderline and malignant tumors, similarly to previous reports, possibly reflecting the
Magro, Cynthia M; Abraham, Ronnie M; Guo, Ruifeng; Li, Shibo; Wang, Xuan; Proper, Steven; Crowson, A Neil; Mihm, Martin
Deep penetrating nevi (DPN) are a relatively uncommon subtype of melanocytic nevi. A small subset of these lesions exhibit atypical features (cytologic and architectural atypia, mitotic activity) seen in melanoma. These lesions we term the deep penetrating nevus-like borderline tumor. Unequivocal melanomas can show overlapping morphologic features of DPN, which have been termed plexiform melanomas. 40 cases of DPN-like borderline tumor were identified along with 6 cases of plexiform melanoma. Clinical follow up was obtained, along with cytogenetic analysis in the form of fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). The DPN-like borderline tumor cases included 24 females and 16 males. Of sentinel lymph node biopsies performed, 1/3 of cases showed lymph node involvement. All patients where an aggressive clinical approach was adopted remain free of disease. All 6 DPN-like borderline tumor cases tested by CGH showed normal cytogenetics, as did 7 of 9 cases tested by FISH. Of the plexiform melanomas, 4/6 patients died of disease. In 3 cases there was morphologic progression from a DPN-like borderline tumor to overt melanoma. In one case of progression, cytogenetics was normal in the DPN-like borderline tumor and then abnormal in the progressed melanoma. DPN-like borderline tumors are melanocytic tumors associated with a high incidence of regional lymph node disease and exhibiting the potential for melanoma progression despite a normal cytogenetic profile. Patients with these lesions should be aggressively managed, with at least complete re-excision and consideration of sentinel node biopsy, regardless of cytogenetic data.
Dina, I; Ginghina, O; Iacobescu, C; Vrabie, C; Gidea, C; Munteanu, R; Iosifescu, R; Iordache, N
Cystic lesions of the pancreas are relatively rare entities but have been increasingly diagnosed in recent years due to advanced imaging techniques. This category encompasses pancreatic pseudocyst as well as a wide range of pancreatic tumors with benign behavior, borderline or primary malignant. Serous cystadenoma of the pancreas represents the most common benign pancreatic tumor, with a very low but well recognized malignant potential. The clinical presentation varies according to its size; small tumors may be asymptomatic and discovered incidentally, while large tumors are more likely symptomatic. We report the case of a female patient presenting with non-specific left abdominal pain, who was diagnosed through a CT scan with a caudal pancreatic tumor. The patient underwent spleen-preserving distal pancreatectomy. The result of the histopathological examination revealed a serous cystadenoma.
Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan
Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.
Shah, Lopa; Tiesi, Gregory; Bamboat, Zubin; McCain, Donald; Siegel, Andrew; Mannion, Ciaran
Metastatic cancer to the pancreas accounts for less than 2% of all pancreatic malignancies. In contrast to other metastatic tumors, renal cell carcinoma (RCC) has a propensity to metastasize as a solitary pancreatic lesion. While symptomatic patients may present with obstructive jaundice, abdominal pain, or gastrointestinal bleeding, the diagnosis of metastatic pancreatic involvement is often made in asymptomatic patients, during follow-up evaluation in the aftermath of an initial diagnosis of renal cell carcinoma. Microcystic serous cystadenoma of the pancreas is an uncommon pancreatic exocrine neoplasm that morphologically resembles conventional (clear cell) RCC, in so far as both tumors are characterized by neoplastic cells with clear cytoplasm, relatively uniform nuclei and scant associated tumor stroma. Herein, we report 2 immunohistochemically confirmed cases of unsuspected metastatic RCC to the pancreas, with the metastatic tumor in each case confined to a preexisting microcystic serous cystadenoma of the pancreas.
Takemoto, Shuji; Kawano, Ryosuke; Honda, Kazumi; Nakazono, Aki; Shimamatsu, Kazuhide
Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.
Introduction Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Case presentation Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. Conclusion We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery. PMID:22583977
Ciucci, Alessandra; Zannoni, Gian Franco; Buttarelli, Marianna; Lisi, Lucia; Travaglia, Daniele; Martinelli, Enrica; Scambia, Giovanni; Gallo, Daniela
The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2 modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERα expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ERα-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2 on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC.
Xing, Deyin; Rahmanto, Yohan Suryo; Zeppernick, Felix; Hannibal, Charlotte G; Kjaer, Susanne K; Vang, Russell; Shih, Ie-Ming; Wang, Tian-Li
Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of serous borderline tumor (SBT) to invasive low grade serous carcinoma (LGSC) remains largely unknown. While mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression. In this study, we analyzed NRAS exon 3 mutational status in 98 cases that were diagnosed with SBT/atypical proliferative serous tumor (SBT/APST), non-invasive LGSC (niLGSC), or invasive LGSC (iLGSC). Of the latter, NRAS Q61R (CAA to CGA) mutations were detected in only 2 of 56 (3.6%) cases. The same mutation was not detected in any of the SBT/APSTs or niLGSCs. Mutational analysis for hotspots in KRAS and BRAF demonstrated a wildtype pattern of KRAS and BRAF in one of the NRAS-mutated cases. Interestingly, another LGSC case with NRAS mutation harbored a concurrent BRAF V600L mutation. These findings indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC. Further studies to identify other oncogenic drivers of LGSC progression is warranted. Copyright © 2017. Published by Elsevier Inc.
Tang, Shangguo; Onuma, Kazu; Deb, Pratima; Wang, Eric; Lytwyn, Alice; Sur, Monalisa; Daya, Dean
Serous tubal intraepithelial carcinoma (STIC) has been implicated in the pathogenesis of pelvic serous carcinoma. We hypothesized that, if this is the case, the frequency of STIC should be substantially lower in endometrial serous carcinomas, in nonserous gynecologic malignancies, and in benign gynecologic neoplasms than in ovarian or peritoneal serous carcinomas. From 2007 to 2009 the fallopian tubes of 342 consecutive gynecologic cases were entirely submitted for histology using the Sectioning and Extensively Examining the FIMbriated end protocol. This study included 300 of these cases (277 TAH-BSO, 23 BSO) after exclusion. The hematoxylin and eosin-stained slides from the fallopian tubes were independently reviewed by 2 gynecologic pathologists who were blinded to all other findings; disagreements were resolved by a third pathologist. Among 46 cases of ovarian malignancies, STIC was identified in 6 (18.8%) of 32 cases of serous carcinoma, but not in any other subtype. Similarly, STIC coexisted in 4 (14.3%) of 28 cases of endometrial serous carcinoma; however, no STIC was identified in any of the 74 cases of nonserous endometrial malignancies. STIC was identified in 2 (28.6%) of 7 cases of peritoneal serous carcinoma. No STIC was identified among 15 nongynecologic malignancies, 90 cases of benign conditions, and 27 cases of other conditions including 4 cases of cervical adenocarcinoma in situ and high-grade cervical intraepithelial lesions, 8 cases of endometrial atypical complex hyperplasias, and 15 cases of ovarian borderline tumors. In conclusion, the fallopian tube may be the origin of some pelvic serous carcinomas. Other possibilities that may explain the origin of pelvic high-grade serous carcinoma are discussed. Given that STIC coexisted with 14% of endometrial serous carcinomas, a more unifying theory may be that gynecologic serous carcinomas and STIC are multifocal lesions.
Bartel, Frank; Balschun, Katharina; Gradhand, Elise; Strauss, Hans G; Dittmer, Jürgen; Hauptmann, Steffen
Members of the CCN [cystein-rich 61 (Cyr61)/connective tissue growth factor (CTGF)/nephroblastoma (NOV)] protein family are involved in the regulation of cellular proliferation, apoptosis, and migration and are also assumed to play a role in carcinogenesis. Therefore, we performed a retrospective study to investigate the immunohistochemical expression of both Cyr61 and CTGF in 92 borderline tumors (BOTs) and 107 invasive carcinomas of the ovary (IOCs). To determine their diagnostic and prognostic value, we correlated protein expression with clinicopathologic factors including overall and disease-free survival. Cyr61 and CTGF were found to be inversely expressed in both BOTs and IOCs, with a stronger expression of Cyr61 in IOCs. Moreover, Cyr61 was found to be preferentially expressed in high-grade serous carcinomas, whereas CTGF was found more frequently in low-grade serous carcinomas. Weak Cyr61 levels correlated with both low estrogen receptor and p53 expression (P=0.038, P=0.04, respectively). However, no association was observed between CTGF, estrogen receptor, and p53 expression levels in IOCs. Regarding prognosis, Cyr61 was found to be of no value, but the loss of CTGF was found to be associated with a poor prognosis in multivariate analysis of overall (relative risk 2.8; P=0.050) and disease-free (relative risk 2.3; P=0.031) survival. Cyr61 and CTGF are inversely expressed in BOTs and IOCs, and loss of CTGF independently indicates poor prognosis in IOCs.
Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard
Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651
Wang, Hui; Wang, Xiang; Wang, Cheng-Feng
Phyllodes tumors of the breast are rare fibroepithelial lesions, so relatively little is known about this disease entity. The present study was designed to identify differences in clinical features between benign borderline and malignant phyllodes tumors. Data from 246 women with phyllodes tumors of the breast treated in Cancer Hospital Chinese Academy of Medical Sciences between 2002 and 2012 were collected and analyzed, including age at presentation, age at treatment, course, size of primary tumor, location, histological type, type of surgery and treatment, local recurrence, distant metastasis, fibroadenoma history, disease-free survival and number of mitosis per 10hpf. There are 125 (55%) benign, 55 (24%) borderline and 47 (21%) malignant tumors. In univariate analysis, average age at presentation, average age at treatment, size of primary tumor, ulceration or not, type of primary surgery, distant metastasis and number of mitosis per 10 hpf turned out to be statistically different among the three PT types (p=0.014, 0.018, <0.000, 0.003, <0.000, 0.001 and <0.000, respectively), while recurrence and disease-free survival (DFS) demonstrated trends for statistical significance (P =0.055 and 0.060, respectively). Multivariate analysis revealed distant metastasis and excision were significantly different in benign, borderline and malignant phyllodes tumors of the breast (p=0.041 and 0.018, OR=0.061 and 0.051). At the same time, size of primary tumor with p=0.052 tended to be different between groups (OR=1.127). However, age at treatment, ulceration and DFS showed no statistically significant variation (p=0.400, 0.286 and 0.413, respectively). Benign borderline and malignant phyllode tumors have different distant metastasis risk, different primary tumor size and different surgical procedures, and malignant PTs are more likely to be bigger and to metastasize.
Adams, Sarah F.; Levine, Douglas A.; Cadungog, Mark G.; Hammond, Rachel; Facciabene, Andrea; Olvera, Narciso; Rubin, Stephen C.; Boyd, Jeff; Gimotty, Phyllis A.; Coukos, George
Background We sought to determine whether tumor-infiltrating lymphocytes and/or tumor mitotic activity could identify subgroups of patients with advanced serous epithelial ovarian cancer who would maximally benefit from aggressive surgical cytoreduction. Methods Snap-frozen specimens from 134 consecutive patients with stage III or IV serous or poorly differentiated ovarian adenocarcinoma undergoing primary debulking surgery from a single US institution were characterized based on CD3+, CD8+, FoxP3+ tumor infiltrating lymphocytes, and Ki67 expression. Kaplan-Meier survival curves were estimated and compared using a log-rank statistic. A multivariate Cox model was used to estimate adjusted hazard ratios (HR). Interactions were modeled using recursive partitioning based on maximal prognostic differentiation. Results Brisk intraepithelial CD8+ cells (p=0.035) and low Ki67 expression (p=0.042) portended prolonged survival. T cell infiltration was more likely to occur in tumors with high proliferation index. Patients whose tumors exhibited low Ki67 expression and high intraepithelial CD8+ frequency had a 5-year survival rate of 73.3%. Patients with aggressive tumor behavior, i.e. whose tumors exhibited low frequency of intraepithelial CD8+ T cells or high Ki67 expression were more likely to draw benefit from aggressive surgical cytoreduction. Survival was similar for patients with brisk CD8+ T cells who had optimal or suboptimal debulking. Likewise, survival was similar for patients with low Ki67 expression who had optimal or suboptimal debulking. Conclusions These novel interactions of T cells, tumor proliferation index and surgical treatment reveal for the first time that biological prognosticators may be useful for surgical decision making in ovarian cancer. PMID:19472394
Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P
Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.
Park, Sung Yoon; Oh, Young Taik; Jung, Dae Chul
There is overlap in imaging features between borderline and benign ovarian tumors. To analyze diagnostic performance of magnetic resonance imaging (MRI) combined with tumor markers for differentiating borderline from benign ovarian tumor. Ninety-nine patient with MRI and surgically confirmed ovarian tumors 5 cm or larger (borderline, n = 37; benign, n = 62) were included. On MRI, tumor size, septal number (0; 1-4; 5 or more), and presence of solid portion such as papillary projection or septal thickening 0.5 cm or larger were investigated. Serum tumor markers (carbohydrate antigen 125 [CA 125] and CA 19-9) were recorded. Multivariate analysis was conducted for assessing whether combined MRI with tumor markers could differentiate borderline from benign tumor. The diagnostic performance was also analyzed. Incidence of solid portion was 67.6% (25/37) in borderline and 3.2% (2/62) in benign tumors (P < 0.05). In all patients, without combined analysis of MRI with tumor markers, multivariate analysis revealed solid portion (P < 0.001) and CA 125 (P = 0.039) were significant for predicting borderline tumors. When combined analysis of MRI with CA 125 ((i) the presence of solid portion or (ii) CA 125 > 44.1 U/mL with septal number ≥5 for borderline tumor) is incorporated to multivariate analysis, it was only significant (P = 0.001). The sensitivity, specificity, PPV, NPV, and accuracy of combined analysis of MRI with CA 125 were 89.1%, 91.9%, 86.8%, 93.4, and 90.9%, respectively. Combined analysis of MRI with CA 125 may allow better differentiation between borderline and benign ovarian tumor compared with MRI alone. © The Foundation Acta Radiologica 2015.
da Silva, Cléber Sérgio; Adad, Sheila Jorge; Saldanha, João Cristiane; Cançado, Cristiane Gobbo; Bachi, Carlos; Murta, Eddie Fernando Candido
We present a rare case of a 68-year-old postmenopausal woman with a mobile, hard, and painless pelvic abdominal mass that was palpated to the umbilical scar. Ultrasonography demonstrated a solid mass in the upper pole of the right kidney and a predominantly solid pelvic abdominal mass. Serum testosterone was 413 ng/dL. The patient underwent laparotomy on the renal tumor, which was thought to have a probable ovarian metastasis. Bilateral ovariectomy and right nephrectomy were performed. Immunohistochemical and histopathologic assessment identified a right ovarian Sertoli cell tumor, a left ovarian serous cystadenoma, and a mixed epithelial-stromal tumor in the kidney with positive hormonal receptor. Because our patient had an ovarian neoplasm producing steroids and a kidney tumor expressing hormonal receptors, the hypothesis of possible endocrine dependence in the pathogenesis of mixed epithelial stromal tumor is reinforced.
Tello, Mariela; Oscanoa, Monica; Dueñas, Milagros; Castro, Haydee; Latorre, Alan
Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID:26558123
Bastos, Eugenia Maria Chaves De Moraes
Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced
Dina, I; Ginghina, O; Iacobescu, C; Vrabie, C; Gidea, C; Munteanu, R; Iosifescu, R; Iordache, N
Cystic lesions of the pancreas are relatively rare entities but have been increasingly diagnosed in recent years due to advanced imaging techniques. This category encompasses pancreatic pseudocyst as well as a wide range of pancreatic tumors with benign behavior, borderline or primary malignant. Serous cystadenoma of the pancreas represents the most common benign pancreatic tumor, with a very low but well recognized malignant potential. The clinical presentation varies according to its size; small tumors may be asymptomatic and discovered incidentally, while large tumors are more likely symptomatic. We report the case of a female patient presenting with non-specific left abdominal pain, who was diagnosed through a CT scan with a caudal pancreatic tumor. The patient underwent spleen-preserving distal pancreatectomy. The result of the histopathological examination revealed a serous cystadenoma. PMID:25914751
Moutte, Amandine; Chopin, Nicolas; Faure, Christelle; Beurrier, Frédéric; Ho Quoc, Christophe; Guinaudeau, Florence; Treilleux, Isabelle; Carrabin, Nicolas
Phyllodes tumors (PT) are uncommon fibroepithelial breast neoplasms and there is currently no clear consensual treatment for these tumors. The aim of our study was to evaluate the surgical management and outcome of benign and borderline PT. We retrospectively assessed 76 cases of benign or borderline PT managed at the Leon Berard comprehensive cancer center in Lyon, France between July 2003 and December 2013. The mean age at diagnosis was 37.9 years and the median follow-up was 58 months. Seventy-five patients (99%), with a mean tumor size of 27 mm, underwent a breast-conserving procedure. The tumor margins were considered positive (when the tumor was present at the inked surgical section) in seven of 76 cases (9%) and negative in 65 out of 76 cases (86%). We observed the presence of small negative surgical margins <10 mm in 89% and <1 mm in 71% of the patients. Although no re-excision was performed to increase these margins, we did not see any increase in the local recurrence rate (4%) when compared to recurrence rates reported in the literature. We thus suggest that systematic revision surgery for close or positive surgical margins for benign PT should not be systematically performed. However, as recurrences occur within 2 years of initial excision, we recommend a regular clinical and imaging follow-up especially during this period for which patient's compliance is essential. © 2016 Wiley Periodicals, Inc.
Singh, Harmeet; Li, Ying; Fuller, Peter J; Harrison, Craig; Rao, Jyothsna; Stephens, Andrew N; Nie, Guiying
Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homologous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors.Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, endometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcinomas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry.Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall.Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.
Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan
Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076
Franchi, Dorella; Boveri, Sara; Radice, Davide; Portuesi, Rosalba; Zanagnolo, Vanna; Colombo, Nicoletta; Testa, Antonia Carla
Borderline ovarian tumors are generally diagnosed in young women. Because of the young age of patients at first diagnosis and at recurrence, and given the good prognosis of borderline ovarian tumors, a conservative surgical approach in those women who wish to preserve their fertility is advised. In this scenario, transvaginal ultrasound examination plays a key role in the detection of borderline ovarian tumor recurrence, and in assessment of amount of normal functioning parenchyma remaining. To date, no data are available about the natural history of borderline ovarian tumor recurrence. The aim of the study was to determine growth rate of recurrent ovarian cysts by a scheduled follow-up by ultrasound examination, in women previously treated with fertility-sparing surgery due to borderline ovarian tumors. In this prospective observational study, we collected data from 34 patients previously treated with fertility-sparing surgery due to borderline ovarian tumors, who had a suspicious recurrent lesion. The patients underwent transvaginal ultrasonographic examination every 3 months, until the clinical setting recommended proceeding with surgery. According to cyst size at study entry, they were categorized into 3 groups: ≤10 mm, 10-20 mm, and >20 mm. Summary statistics for cyst size, growth rate, and the probability of remaining within the same dimension category at first ultrasound during the follow-up were also obtained. For each cyst the growth rate was calculated as the slope of the linear interpolation between 2 consecutive measurements. Follow-up timing (P < .001), cyst size (P < .001), and micropapillary pattern (P < .001) were factors significantly affecting the cyst growth both in univariate and multivariate analysis. According to size category at first ultrasound, growth rate ranges from a minimum of 0.06 mm/mo for cysts <10 mm up to 1.92 mm/mo for cysts >20 mm. The final histology of all recurrent lesions confirmed the same histotype of primary borderline
Labidi-Galy, S I; Clauss, A; Ng, V; Duraisamy, S; Elias, K M; Piao, H-Y; Bilal, E; Davidowitz, R A; Lu, Y; Badalian-Very, G; Györffy, B; Kang, U-B; Ficarro, S; Ganesan, S; Mills, G B; Marto, J A; Drapkin, R
High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through the activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into the examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting.
Armes, Jane E; Lourie, Rohan; de Silva, Melanie; Stamaratis, Georgia; Boyd, Alison; Kumar, Beena; Price, Gareth; Hyde, Simon; Allen, David; Grant, Peter; Venter, Deon J
Dysfunction of proteins involved in the G1 to S transition of the cell cycle, such as p16(INK4A) and RB1, is common in many cancer types. A screen of p16 protein expression was performed in benign, borderline, and invasive ovarian tumors, together with endometrial cancers, aligned on a tissue microarray. We observed frequent p16 overexpression in serous papillary carcinomas of ovarian and endometrial origin. An extended cohort of ovarian serous papillary carcinomas was examined to further evaluate the frequency of p16 overexpression. Strong, uniform staining in the majority of cancer cells occurred commonly in invasive serous papillary ovarian cancers, particularly in grade 3 carcinomas. RB1 protein expression abnormalities were rare. Our data indicate that abnormalities in the retinoblastoma pathway, as determined by p16 overexpression, are common in serous papillary carcinomas and are probably an early event.
Ibrahim, Wael S
Phyllodes tumors are group of biphasic fibroepithelial tumors of the breast of varying malignant potential, ranging from benign tumors to fully malignant sarcomas. According to the Egyptian National Cancer Institute, female malignant cases showed appreciable increase in the recent time period for breast cancer with the malignant phyllodes tumors representing 0.41% of cases in the year 2003-2004. This is an immunohistochemical study to compare CD10 expression in benign, borderline, and malignant phyllodes tumors, in order to highlight its diagnostic and prognostic values. This study conducted 34 Egyptian female cases of phyllodes tumors of different grades to be studied histologically and immunohistochemically using antibodies against CD10. The Chi-square test was used to determine differences in CD10 expression between benign, borderline, and malignant tumors. One-way ANOVA test was used to determine whether the difference was significant. Significance was established at P<0.05. In the 24 cases of benign phyllodes tumors, only four cases (16.7%) showed positive CD10 reactivity. Three cases (60%) out of five borderline phyllodes tumors showed positive CD10 reactivity, while four (80%) out of five cases of malignant phyllodes tumors showed positive CD10 staining. From these highly significant results, we believe that there is a strong correlation between CD10 expression and tumor grade, which could be an important observation that may have both diagnostic and prognostic implications as well as promising potential target for development of novel therapies.
Adur, Javier; Pelegati, Vitor B.; Costa, Leverson F. L.; Pietro, Luciana; de Thomaz, Andre A.; Almeida, Diogo B.; Bottcher-Luiz, Fatima; Andrade, Liliana A. L. A.; Cesar, Carlos L.
We used a multimodal nonlinear optics microscopy, specifically two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG/THG) microscopies, to observe pathological conditions of ovarian tissues obtained from human samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with hematoxylin and eosin (H&E) stored for a very long time, and that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG-THG microscopies in a stored file of H&E stained samples of human ovarian cancer to obtain complementary information about the epithelium/stromal interface, such as the transformation of epithelium surface (THG) and the overall fibrillary tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able to not only differentiate between cancerous and healthy tissue, but can also distinguish between normal, benign, borderline, and malignant specimens according to their collagen disposition and compression levels within the extracellular matrix. The dimensions of the layers of epithelia can also be measured precisely and automatically. Our data demonstrate that optical techniques can detect pathological changes associated with ovarian cancer.
Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.
Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice. PMID:19700937
Wang, Hui; Wang, Xiang; Wang, Chengfeng
To explore the prognosis of benign, borderline and malignant phyllodes tumors of the breast. Data from 246 women with phyllodes tumors of the breast treated in the Cancer Hospital, Chinese Academy of Medical Sciences between January 2002 and December 2012, were collected and analyzed retrospectively. The patients were followed-up for a median of 48 months (range 1-138 months). Kaplan-Meier analysis and Cox proportional hazard model were used to analyze the factors affecting the disease-free survival. Among the 246 patients, 65 were dropped out from the follow-up. 56 patients had local recurrence, 5 patients had distant metastasis, while one case had both local recurrence and distant metastasis. The median disease-free survival time was 39 months. Kaplan-Meier survival analysis revealed that fibroadenoma history and type of primary surgery were associated to the disease-free survival of phyllodes tumors of the breast (P<0.001, P=0.043), while histological type and primary tumor size had no significant relationship with the disease-free survival (P=0.083, P=0.974). The multivariate Cox proportional hazard model showed that type of primary surgery, fibroadenoma history and histological types are all independent factors affecting the disease-free survival (P=0.009, P=0.001 and P<0.001). Phyllodes tumors of the breast have a relatively good prognosis on the whole. Type of primary surgery, fibroadenoma history and histological type are independent factors predicting the disease-free survival of patients with phyllodes tumors of the breast.
Tomita, Tatsuo; Ren, Yafei; Davis, Marilyn; Tawfik, Ossama
The patient was 80 years old when she initially presented with a left breast mass. Originally, a needle biopsy showed benign stromal and ductal cells. Five years later, the breast mass increased in size and a core needle biopsy showed a biphasic intraductal papillomatous tumor with cellular stroma. Eighteen months later, another biopsy was taken from the breast mass, revealing a well-developed phyllodes tumor (PT) of borderline malignancy. One month later, a simple mastectomy was performed for this 87-year-old woman. Histolopathologic and immunohistochemical studies, including estrogen and progesterone receptors, Ki-67 and p53, performed on tissues from the different biopsy specimens confirmed the progressive transition of the tumor in a 7 year period. An increase in mitotic activity was noted in the later samples. Similarly, percentages of p53- and Ki-67-positive cells were much higher in the stromal and ductal cells of the later samples compared to the original specimen. These findings support the notion that Ki-67 and p53 immunohistochemical staining may be used as simple and practical markers for the evaluation of the malignant potential of PT.
Morris, Cyllene R; Liu, Lihua; Rodriguez, Anne O; Cress, Rosemary D; Snipes, Kurt
Borderline ovarian tumors (BOT) became no longer reportable in 2001, and few registries still collect information on these still poorly understood tumors. This study's objective was to describe epidemiologic features, trends, and survival of BOTs compared with those of low-grade (LG) and high-grade (HG) epithelial ovarian cancer (EOC) in the large and diverse population of California. Data from the California Cancer Registry were used to examine demographic and tumor characteristics among women diagnosed with BOT (n = 9,786), LG-EOC (n = 3,656), and HG-EOC (n = 40,611) from 1988 to 2010. Annual percent changes in BOT and LG-EOC incidence rates were estimated using Joinpoint regression; 5-year relative survival was calculated for both BOTs and LG-EOCs by age, race/ethnicity, and histology. Age-adjusted incidence rates of BOT in 2009 were 3.1, 2.3, 2.2, and 1.4 per 100,000 among whites, Latinas, African Americans, and Asian/Pacific Islanders, respectively. Incidence rates for LG-EOC decreased by 2.2 % per year; rates for BOT increased by 7.3 % per year until 1993, remained unchanged until 2006, and seemed to decline thereafter. Compared with LG-EOCs, BOTs were diagnosed in higher frequency among Latinas, at younger age, and were more likely to affect only one ovary. Overall, 5-year relative survival for BOT was 98.9 %; among women diagnosed with stage IV BOT, survival was 77.1 %. In this study, differences between BOTs and LG-EOCs were marked but varied substantially by histologic subtype and were far less dramatic than differences between BOTs and HG-EOCs. Findings underscore the importance of understanding these enigmatic tumors.
Sadlecki, Pawel; Walentowicz, Pawel; Bodnar, Magdalena; Marszalek, Andrzej; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata
Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were
Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana
Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.
Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar
Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484
Menczer, Joseph; Chetrit, Angela; Sadetzki, Siegal
The classically recommended surgical treatment of borderline ovarian tumors (BOTs) includes hysterectomy in addition to bilateral adnexectomy. Possible reasons for hysterectomy might be a high frequency of uterine involvement and its favorable effect on survival. The purpose of the present study was to assess the frequency of uterine involvement in patients with BOTs and the effect of hysterectomy on survival. All incident cases of histological confirmed BOTs diagnosed in Israeli Jewish women between March 1 1994 and June 30 1999, were identified. Clinical and pathological characteristics were abstracted from medical records. Patients with tumors grossly confined to the ovaries (apparently stage I) were considered to have had surgical staging when at least hysterectomy, bilateral salpingooophorectomy, omentectomy and pelvic lymph node sampling were done. The study group comprised 225 patients. Hysterectomy was performed in 147 (65.31%) patients and uterine involvement was present in only 3 (2.0%) of them. The 13 year survival of the total group of patients was 85.8% and of those in apparent stage I, 88.5%. Among patients with tumors apparently confined to the ovaries, no significant survival difference was observed between unstaged and surgically staged patients. There was also no survival difference between the overall staged and unstaged patients and between patients in stages II-III who did and did not undergo hysterectomy. Our data indicate that the rate of uterine involvement in BOT is low and that hysterectomy does not favorably affect survival. The necessity of hysterectomy in BOT patients is questioned. Copyright © 2012 Elsevier B.V. All rights reserved.
Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S
The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.
Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.
Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789
Chuong, Michael D; Frakes, Jessica M; Figura, Nicholas; Hoffe, Sarah E; Shridhar, Ravi; Mellon, Eric A; Hodul, Pamela J; Malafa, Mokenge P; Springett, Gregory M; Centeno, Barbara A
While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.
Della Pepa, Chiara; Tonini, Giuseppe; Santini, Daniele; Losito, Simona; Pisano, Carmela; Di Napoli, Marilena; Cecere, Sabrina Chiara; Gargiulo, Piera; Pignata, Sandro
Low Grade Serous Ovarian Carcinoma, LGSOC, is certainly a rare disease, accounting for only a small proportion of all ovarian carcinomas, nevertheless in the last decade we have acquired many data about its molecular and clinical features and it has been largely accepted that it has distinct pathogenesis, genetic aberrations and clinical behavior compared to High Grade Serous Ovarian Carcinoma, HGSOC, which is the most common ovarian cancer histotype. A large number of series pointed out the high rate of KRAS and BRAF mutations in LGSOCs and Serous Borderline Tumors, SBLTs, in contrast with their rarity in HGSOC. Such finding, together with the recurrent observation of focus of LGSOC associated with areas of SBLT in the same lesion, led to abandon the traditional histology classification, defining three types of serous carcinomas, in favor of a new dualistic grading system which recognizes only LG and HG carcinomas corresponding to distinct tumorigenesis pathways, the former based on KRAS/BRAF mutations and alteration of the MAP/ERK signaling, the latter characterized by early genetic instability and wild type status of KRAS and BRAF. LGSOC shows favorable overall survival, compared to general ovarian cancer population, but worrying resistance to conventional treatments. MEK inhibitors are emerging as active agents and may well represent an effective therapeutic strategy in the near future.
Trillsch, Fabian; Ruetzel, Jan David; Herwig, Uwe; Doerste, Ulrike; Woelber, Linn; Grimm, Donata; Choschzick, Matthias; Jaenicke, Fritz; Mahner, Sven
Surgery is the cornerstone for clinical management of patients with borderline ovarian tumors (BOT). As these patients have an excellent overall prognosis, perioperative morbidity is the critical point for decision making when the treatment strategy is developed and the primary surgical approach is defined. Clinical and surgical parameters of patients undergoing surgery for primary BOT at our institutions between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparotomy vs. laparoscopy). A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Complete surgical staging was achieved in 33 patients at primary surgical approach (31.4%) frequently leading to formal indication of re-staging procedures. Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy can be considered for staging of patients with BOT if this appears feasible. An algorithm for the surgical management of BOT patients has been developed.
Anastasi, Emanuela; Porpora, Maria Grazia; Pecorella, Irene; Bernardo, Silvia; Frati, Luigi; Benedetti Panici, Pierluigi; Manganaro, Lucia
We present a case of a 58-year-old menopausal woman referred to our hospital for the presence of large pelvic masses diagnosed by clinical examination and pelvic ultrasound. MRI examination showed voluminous bilateral capsulated multilocular ovarian cysts slightly hyperintense on T1-weighted images with thick septa and small papillary projections. CT scan confirmed the MRI findings. Among the ovarian tumor markers analyzed (CA125, HE4, and CA72.4), only Ca125 was slightly increased (48 U/ml). These data were suggestive of mucinous ovarian tumor. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, appendectomy, and multiple peritoneal biopsies. Pathological examination revealed bilateral borderline mucinous ovarian tumor with superficial atypical implants. Nine months later, the patient complained of left coxofemoral pain and underwent a PET/TC total body that suggested pubic bone metastases. Ovarian tumor markers were analyzed, and a second PET/TC was performed. CA125 was 252 U/ml, HE4 62 pM/L, and CA72.4 > 100 U/Ml. PET/TC was suggestive of peritoneal carcinosis. The patient was readmitted to the hospital. Clinical examination revealed small vaginal nodules. All nodules were excised. Microscopic analysis of all specimens revealed metastatic mucinous adenocarcinoma of intestinal type.The case shows that even a slight CA125 increase in the presence of a borderline ovarian tumor should not be overlooked since it can be indicative of a progressive disease. This case also highlights its additional diagnostic value when serum CA125 analysis is used in conjunction with MRI and CT imaging for the prognosis of mucinous borderline ovarian tumors (mBOTs).
Li, Huiwen; Cui, Xuelian; Chen, Dingbao; Yang, Yang; Piao, Junjie; Lin, Zhenhua; Yan, Guanghai; Shen, Danhua
T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, was originally identified as an invasion- and metastasis-inducing gene in T lymphoma cells. High expression levels of the human Tiam1 gene have been found in numerous human malignancies, suggesting a potential role as a modifier of tumor initiation and progression. However, little is known about the status of Tiam1 in ovarian carcinoma. The present study aimed to investigate the clinicopathological significance of high Tiam1 expression in serous ovarian carcinoma. Immunohistochemical staining for Tiam1 was performed in 182 patients with serous ovarian carcinoma, in 76 patients with ovarian borderline tumors and in 72 patients with benign ovarian tumors. Immunofluorescence staining was also performed to detect the subcellular localization of Tiam1 protein in SK-OV-3 ovarian carcinoma cells. The correlations between high Tiam1 expression and the clinicopathological features of the ovarian carcinomas were evaluated by the χ2 test and Fisher's exact test. The overall survival (OS) rates were calculated by the Kaplan-Meier method, and the association between prognostic factors and patient survival was analyzed by the Cox proportional hazard model. Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. Strongly-positive Tiam1 protein expression was observed in 59.3% (108/182) of ovarian carcinomas, which was significantly higher than in benign serous tumors (12.5%; 9/72). Moreover, the rate of strongly-positive Tiam1 expression in borderline serous tumors (31.6%; 24/76) was also significantly higher than that in benign serous tumors. High Tiam1 protein expression was closely associated with a high histological grade, metastasis, advanced clinical stage and lower OS rates in ovarian carcinoma. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with metastasis and clinical stage, in patients with ovarian carcinoma. In
Li, Huiwen; Cui, Xuelian; Chen, Dingbao; Yang, Yang; Piao, Junjie; Lin, Zhenhua; Yan, Guanghai; Shen, Danhua
T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, was originally identified as an invasion- and metastasis-inducing gene in T lymphoma cells. High expression levels of the human Tiam1 gene have been found in numerous human malignancies, suggesting a potential role as a modifier of tumor initiation and progression. However, little is known about the status of Tiam1 in ovarian carcinoma. The present study aimed to investigate the clinicopathological significance of high Tiam1 expression in serous ovarian carcinoma. Immunohistochemical staining for Tiam1 was performed in 182 patients with serous ovarian carcinoma, in 76 patients with ovarian borderline tumors and in 72 patients with benign ovarian tumors. Immunofluorescence staining was also performed to detect the subcellular localization of Tiam1 protein in SK-OV-3 ovarian carcinoma cells. The correlations between high Tiam1 expression and the clinicopathological features of the ovarian carcinomas were evaluated by the χ(2) test and Fisher's exact test. The overall survival (OS) rates were calculated by the Kaplan-Meier method, and the association between prognostic factors and patient survival was analyzed by the Cox proportional hazard model. Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. Strongly-positive Tiam1 protein expression was observed in 59.3% (108/182) of ovarian carcinomas, which was significantly higher than in benign serous tumors (12.5%; 9/72). Moreover, the rate of strongly-positive Tiam1 expression in borderline serous tumors (31.6%; 24/76) was also significantly higher than that in benign serous tumors. High Tiam1 protein expression was closely associated with a high histological grade, metastasis, advanced clinical stage and lower OS rates in ovarian carcinoma. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with metastasis and clinical stage, in patients with ovarian carcinoma. In
Teer, Jamie K; Yoder, Sean; Gjyshi, Anxhela; Nicosia, Santo V; Zhang, Chaomei; Monteiro, Alvaro N A
Epithelial ovarian cancer is a leading cause of death in gynecological cancers. While several systematic studies have revealed the mutation landscape of serous epithelial ovarian cancer, other non-serous subtypes of the disease have not been explored as extensively. Here we conduct exome sequencing of nine non-serous epithelial ovarian tumors (six endometrioid and three mucinous) and their corresponding normal DNA as well as a tumor-only granulosa cell sample. We integrated the exome data with targeted gene sequencing for 1,321 genes selected for their involvement in cancer from additional 28 non-serous ovarian tumors and compared our results to TCGA ovarian serous cystadenocarcinoma and uterine corpus endometrial carcinomas. Prevalence of TP53 mutations in non-serous was much lower than in serous epithelial OC, whereas the prevalence of PIK3CA, PIK3R1, PTEN, CTNNB1, ARID1A, and KRAS was higher. We confirmed the high prevalence of FOXL2 and KRAS mutations in granulosa cell tumors and in mucinous tumors, respectively. We also identified POLE proofreading domain mutations in three endometrioid ovarian tumors. These results highlight mutational differences between serous and non-serous ovarian cancers, and further distinguish different non-serous subtypes.
Lockyer, Megan G; Deavers, Michael T; Zarrin-Khameh, Neda
A 64-yr-old postmenopausal woman with high-grade squamous intraepithelial lesion and atypical glandular cell of undetermined significance on her Pap test was found to have endometrial serous carcinoma (high grade) involving a polyp in a subsequent endometrial biopsy. She underwent hysterectomy and bilateral salpingo-oophorectomy with multiple biopsies of the peritoneum. Microscopic examination of the entirely submitted uterus showed no residual serous carcinoma. Multiple foci of low-grade serous tumor with extensive calcifications and psammoma bodies were identified on the surfaces of the left fallopian tube, ovaries, and biopsies of the peritoneum, consistent with peritoneal primary low-grade serous carcinoma. To our knowledge, this is the first reported case of low-grade serous carcinoma of the peritoneum with a concurrent (high-grade) serous carcinoma of the endometrium arising from an endometrial polyp.
Fadare, Oluwole; James, Samuel; Desouki, Mohamed M; Khabele, Dineo
The purpose of this study is to assess whether composite or coordinate immunoexpression patterns of estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor 1 (WT1) gene can significantly distinguish between endometrial serous carcinoma (ESC) and ovarian serous carcinoma (OSC). Immunohistochemical analyses were performed on whole tissue sections from 22 uterus-confined ESCs and on a tissue microarray of 140 high-grade, pan-stage OSCs, using antibodies to ER, PR, and WT-1. Estrogen receptor, PR, and WT1 expressions were present in 37%, 49%, and 81% of OSC, respectively, but these markers were also present in 18%, 27%, and 36% of ESC. The ER+/PR+/WT1+ coordinate profile was identified in 33.6% of OSC but in none of ESC (P = .0006), resulting in a calculated sensitivity and specificity of this profile for OSC of 33.6% and 100%, respectively. By contrast, the ER-/PR-/WT1- coordinate profile was identified in 41% of ESC but in only 6.4% of OSC (P = .0001), resulting in a calculated sensitivity and specificity of this profile for ESC of 50% and 94%. In summary, in the differential diagnosis between OSC and ESC, positivity for all 3 markers favors an extrauterine origin, whereas negativity for all 3 markers is supportive of an endometrial origin. The use of single markers for this purpose is not recommended, as each lacks optimal discriminatory power. Coordinate profiles, in general, have a high specificity but low sensitivity in this differential diagnosis.
Way, Gregory P.; Rudd, James; Wang, Chen; Hamidi, Habib; Fridley, Brooke L.; Konecny, Gottfried E.; Goode, Ellen L.; Greene, Casey S.; Doherty, Jennifer A.
Four gene expression subtypes of high-grade serous ovarian cancer (HGSC) have been previously described. In these early studies, a fraction of samples that did not fit well into the four subtype classifications were excluded. Therefore, we sought to systematically determine the concordance of transcriptomic HGSC subtypes across populations without removing any samples. We created a bioinformatics pipeline to independently cluster the five largest mRNA expression datasets using k-means and nonnegative matrix factorization (NMF). We summarized differential expression patterns to compare clusters across studies. While previous studies reported four subtypes, our cross-population comparison does not support four. Because these results contrast with previous reports, we attempted to reproduce analyses performed in those studies. Our results suggest that early results favoring four subtypes may have been driven by the inclusion of serous borderline tumors. In summary, our analysis suggests that either two or three, but not four, gene expression subtypes are most consistent across datasets. PMID:27729437
Kurman, R J
A new paradigm for the pathogenesis of ovarian cancer has recently been proposed which helps to explain persistent problems in describing the development and diverse morphology of these neoplasms. The paradigm incorporates recent advances in our understanding of the molecular pathogenesis of epithelial 'ovarian' cancer with new insights into the origin of these tumors. Correlated clinicopathologic and molecular genetic studies led to the development of a dualistic model that divides all the various histologic types of epithelial ovarian carcinomas into two broad categories designated 'type I' and 'type II'. The prototypic type I tumor is low-grade serous carcinoma and the prototypic type II tumor is high-grade serous carcinomas (HGSCs). As the serous tumors comprise ∼70% of all epithelial ovarian tumors and account for the majority of deaths, the serous tumors will be the subject of this review. There are marked differences between the low-grade and high-grade serous tumors. Briefly, the former are indolent, present in stage I (tumor confined to the ovary) and develop from well-established precursors, so-called 'atypical proliferative (borderline) tumors,' which are characterized by specific mutations, including KRAS, BRAF and ERBB2; they are relatively genetically stable. In contrast, HGSCs are aggressive, present in the advanced stage, and develop from intraepithelial carcinomas in the fallopian tube. They harbor TP53 mutations in over 95% of cases, but rarely harbor the mutations detected in the low-grade serous tumors. At the time of diagnosis they demonstrate marked chromosomal aberrations but over the course of the disease these changes remain relatively stable. Along with the recent advances in understanding the molecular pathogenesis of these tumors, studies have demonstrated that the long sought for precursor of ovarian HGSC appears to develop from an occult intraepithelial carcinoma in the fimbrial region of the fallopian tube designated 'serous tubal
Dikmen, Kursat; Bostanci, Hasan; Yildirim, Ali Cihat; Sakrak, Omer; Kerem, Mustafa
Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11×9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12×11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pancreatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient's symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.
Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M.; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.
Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women. PMID:27074576
Güler, Sertaç Ata; Uğurlu, M. Ümit; Güllüoğlu, Bahadır M.
Phyllodes tumors are large breast tumors representing only 1% of breast neoplasms and are rarely seen in young women. Histologically, phyllodes tumors are classified as benign, borderline, or malignant based on the characteristics of the stroma. Although wide local excision is recommended for the treatment modality, the reoccurrence rate after surgical excision varies between 36% and 65%, with recurrence more likely in those with the tumor at the margins of excision. Our aim was to report -a case in a 15-year-old girl with a 115-mm borderline phyllodes tumor in her left breast mimicking a juvenile fibroadenoma. We presented a 5-year disease-free follow-up after wide local excision with negative margins.
Gilks, C Blake; Irving, Julie; Köbel, Martin; Lee, Chenghan; Singh, Naveena; Wilkinson, Nafisa; McCluggage, W Glenn
Most nonuterine high-grade serous carcinomas (HGSCs) in women with hereditary breast and ovarian cancer syndrome, due to germline BRCA1/2 mutation, arise in the fimbria of the fallopian tube. However, the site of origin of sporadic HGSC, which is usually widely disseminated at presentation, is not well established. We sought to characterize cases of HGSC discovered incidentally in patients not known to be at high risk, in order to determine the site distribution and possible origin of sporadic HGSC. Incidental microscopic, non-mass-forming cases of serous tubal intraepithelial carcinoma or HGSC in salpingo-oophorectomy specimens in which the tubes and ovaries had been extensively examined were identified. No patients were known or suspected BRCA1/2 mutation carriers. Twenty-one cases were identified (mean age: 57 y). Surgery was for benign disease (n=15), uterine endometrioid adenocarcinoma or atypical hyperplasia (n=3), bladder carcinoma (n=1), or ovarian serous borderline tumor (n=2). In 16 of 21 cases, the lesion was confined to the fallopian tube (unilateral in 14 cases, bilateral in 2). There was serous tubal intraepithelial carcinoma in all cases and invasive HGSC into the underlying lamina propria in 8 of these 16 cases; the invasive focus measured 1.3 cm or less in every case. In the remaining 5 cases, there was fallopian tube mucosal and ovarian involvement; in 2 of these cases, there was also microscopic peritoneal involvement. Sporadic cases of nonuterine HGSC arise in the fallopian tube fimbria in a large majority of cases, providing further evidence for the tubal origin of these neoplasms.
Miyagi, Etsuko; Maruyama, Yasuyo; Mogami, Tae; Numazaki, Reiko; Ikeda, Atsuko; Yamamoto, Hiroshi; Hirahara, Fumiki
We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05). API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.
Puls, L; Heidtman, E; Hunter, J E; Crane, M; Stafford, J
This study evaluated the effect ovarian weight has on the accuracy of frozen sections in serous and mucinous ovarian tumors. The study group included 294 patients who had an initial frozen section (189 serous and 105 mucinous tumors) at surgery. The pathology reports were separated into subgroups (benign, borderline, or malignant). Tumors were broken down into three weight categories: < or = 450 g, > 450 to < or = 1360 g, and > 1360 g. In each weight category, accuracy, sensitivity, specificity, and positive and negative predicative values were calculated on frozen sections. The mean weight of the ovarian tumors was 1042 g. As the weight increased in serous tumors, the sensitivity fell from 96.2 to 93.8 to 75%, respectively, in each weight category. The same trend was noted with mucinous tumors as sensitivity fell from 91.7 to 87.5 to 66.7%, respectively. With an increase in the size of ovarian tumors, a decrease in the sensitivity of frozen section was observed. With tumors greater than 1360 g, sensitivity was only 69%. Twenty-three percent of ovarian tumors revealing borderline diagnosis at frozen section were malignant on the final pathology report, with the greatest misclassification in > 1360-g mucinous tumors (50%). For patients with large ovarian tumors, consideration should be given to performing staging at the time of the initial laparotomy.
Zheng, Wenxin; Xiang, Li; Fadare, Oluwole; Kong, Beihua
Endometrial serous carcinomas constitute no more than 10% of endometrial adenocarcinomas, but frequently present at an advanced stage and have a significantly worse prognosis than the more common low-grade and intermediate-grade endometrioid adenocarcinomas. The neoplasm's potential for rapid tumor progression and the high mortality that is associated with advanced-stage disease underscore the importance of understanding endometrial serous carcinogenesis so that its precancers can be diagnosed and an effective therapeutic intervention can be administered. In this study, the authors summarize the current state of knowledge on endometrial serous carcinogenesis and propose a model for its development based on recent work from our group and published data from other researchers. In this model, endometrial serous carcinoma arises predominantly in the resting endometrium, manifesting first as p53 immunoreactive, morphologically normal endometrial cells (p53 signatures), evolving to endometrial glandular dysplasia (which is the first morphologically identifiable precursor lesion), then to serous endometrial intraepithelial carcinoma (a carcinoma with a noninvasive growth pattern in the uterus but which is not infrequently associated with extrauterine disease), and finally into fully developed serous carcinoma. Endometrial glandular dysplasia is a lesion, which can be diagnosed by routine microscopic evaluation, whose ablation or removal may potentially offer the opportunity to prevent the development of the associated malignancy. The diagnostic criteria, practical applicability, and evidentiary basis for the delineation of this lesion are studied.
Kuhn, Elisabetta; Wang, Tian-Li; Doberstein, Kai; Bahadirli-Talbott, Asli; Ayhan, Ayse; Sehdev, Ann Smith; Drapkin, Ronny; Kurman, Robert J; Shih, Ie-Ming
Aberration in chromosomal structure characterizes almost all cancers and has profound biological significance in tumor development. It can be facilitated by various mechanisms including overexpression of cyclin E1 and centrosome amplification. As ovarian high-grade serous carcinoma has pronounced chromosomal instability, in this study we sought to determine whether increased copy number of CCNE1 which encodes cyclin E1 and centrosome amplification (>2 copies) occurs in its putative precursor, serous tubal intraepithelial carcinoma. We found CCNE1 copy number gain/amplification in 8 (22%) of 37 serous tubal intraepithelial carcinomas and 12 (28%) of 43 high-grade serous carcinomas. There was a correlation in CCNE1 copy number between serous tubal intraepithelial carcinoma and high-grade serous carcinoma in the same patients (P<0.001). There was no significant difference in the percentage of CCNE1 gain/amplification between serous tubal intraepithelial carcinoma and high-grade serous carcinoma (P=0.61). Centrosome amplification was recorded in only 5 (14%) of 37 serous tubal intraepithelial carcinomas, and in 10 (40%) of 25 high-grade serous carcinomas. The percentage of cells with centrosome amplification was higher in high-grade serous carcinoma than in serous tubal intraepithelial carcinoma (P<0.001). Induced expression of cyclin E1 increased the percentage of fallopian tube epithelial cells showing centrosome amplification. Our findings suggest that gain/amplification of CCNE1 copy number occurs early in tumor progression and precedes centrosome amplification. The more prevalent centrosome amplification in high-grade serous carcinoma than in serous tubal intraepithelial carcinoma supports the view that serous tubal intraepithelial carcinoma precedes the development of many high-grade serous carcinomas.
Toyoda, Yasuhiro; Hojo, Shigeyuki; Yoshioka, Setsuko; Kojima, Fumiyoshi; Matsunaga, Hiroki; Fujie, Yujiro; Fukunaga, Hiroki; Ota, Hirofumi; Endo, Wakio; Maeura, Yoshiichi
A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.
Jia, Lin; Yuan, Zeng; Wang, Yiying; Cragun, Janiel M; Kong, Beihua; Zheng, Wenxin
Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.
Gualtieri, C. Thomas C.; And Others
The use of the diagnosis "borderline" was evaluated with 16 children (6 to 13 years old) who were referred for comprehensive evaluation. None met DSM III criteria for borderline personality disorder. The borderline label had a negative impact on some children and was not helpful for treatment planning or disposition. (Author/SEW)
Zhang, Liping; Liu, Yuxin; Hao, Suyang; Woda, Bruce A; Lu, Di
Among various endometrial adenocarcinomas, endometrioid carcinoma can be very difficult to separate from serous carcinomas. Various biomarkers have been studied with proven value, including p53, Ki-67, and p16. In this study, we present data on another biomarker, IMP2, which we believe is sensitive and specific. Using 320 endometrial biopsy cases, we demonstrate that IMP2 is normally expressed in all proliferative and inactive endometrial glandular cells. The pattern of such expression is unchanged in serous carcinomas. IMP2 expression is, however, lost in all cases of endometrioid carcinomas by at least 25% to >95% of tumor cell populations. Therefore, loss of IMP2 expression can differentiate endometrioid from serous carcinomas. Such finding of IMP2 expression remained the same in mixed endometrioid and serous carcinomas; IMP2 expression is lost in all endometrioid components by at least 25% of tumor cell population, whereas it remained diffuse and strong in all serous components of carcinomas.
Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro
The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.
Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka
We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and <1.0 µU/ml, respectively. Following a simple mastectomy, the 24-h postoperative serum IGF-II and insulin levels were 496 ng/ml and 10.0 µU/ml, respectively. The IGF-II levels detected in the phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.
Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell
M.V, Rashmi.; P, Pavithra; G.M, Shivakumarappa
Dermatofibrosarcoma protruberans is a relatively uncommon slow growing, locally aggressive fibrous tumor of the skin. It has a prospensity of progressing to fibrosarcomatous change in 5% of the cases. We present a case of a 56 yr old male with presented to the outpatient department of surgery, Sri Siddhartha Medical College, Tumkur with a chest swelling in 2013. FNAC was inconclusive and the mass was excised. On histopathology, areas of benign fibrohistiocytic tumor, dermatofibrosarcoma protruberans and fibrosarcomatous dermatofibrosarcoma were identified in the same tumor. Immunohistochemistry confirmed the diagnosis of DFSP with fibrosarcomatous change. Although, transformed DFSP is more aggressive, the prognosis is influenced by the extent of excision and with wide excision, there may be little increased risk for recurrence and metastasis over that of conventional DFSP. PMID:27799980
Dorfman, H D; Weiss, S W
A series of 102 benign osteoblastic tumors of multiple skeletal sites was reviewed, and on the basis of their clinical, radiologic, and pathologic features they were classified into three diagnostic categories: osteoid osteoma, osteoblastoma, and aggressive osteoblastoma. A historic review of the development of the nomenclature of benign osteoblastic tumors, with special emphasis on the evolving concept of aggressive and malignant behavior, is presented. Histologic criteria for the recognition of aggressive osteoblastoma are presented and illustrated in connection with the 15 cases so classified in the present series. The differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma is discussed. In defining the problem of differentiating locally aggressive osteoblastic lesions from potentially metastasizing tumors, the authors propose that four categories of these osteoblastic tumors can be defined: (1) Innocuous-appearing low-grade osteosarcomas that resemble osteoblastomas histologically. This mimicry accounts for most errors in diagnosis. (2) Rare osteoblastomas that have undergone spontaneous transformation into osteosarcomas. (3) Very rare, clinically and radiologically typical osteoblastomas that show pseudosarcomatous histologic features but pursue a benign course. (4) Locally aggressive osteoblastomas that are likely to recur, do not metastasize, and show characteristic and recognizable histologic features.
Fležar, Margareta; Us‐Krašovec, Marija; žganec, Mario; Lavrenčak, Jaka; Golouh, Rastko
The aim of the study was to determine optimal hydrolysis time for the Feulgen DNA staining of archival formalin fixed paraffin‐embedded surgical samples, prepared as single cell suspensions for image cytometric measurements. The nuclear texture features along with the IOD (integrated optical density) of the tumor nuclei were analysed by an automated high resolution image cytometer as a function of duration of hydrolysis treatment (in 5 N HCl at room temperature). Tissue blocks of breast carcinoma, ovarian serous carcinoma, ovarian serous tumor of borderline malignancy and leiomyosarcoma were included in the study. IOD hydrolysis profiles showed plateau between 30 and 60 min in the breast carcinoma and leiomyosarcoma, and between 40 and 60 min in the ovarian serous carcinoma and ovarian serous tumor of borderline malignancy. Most of the nuclear texture features remained stable after 20 min of hydrolysis treatment. Our results indicate that the optimal hydrolysis time for IOD and for nuclear texture feature measurements, was between 40 and 60 min in the cell preparations from tissue blocks of three epithelial and one soft tissue tumor. PMID:10866273
Zhen-Zhong, Deng; Zheng, Ning; Liu, Heng; Liao, Dong-Ying; Ye, Xiao-Qin; Zhou, Qiu-Ming; Jie; Li, Huai-Hui; Liu, Qi; Lu, Kang-Min
Psammocarcinoma is a rare form of serous carcinoma of the ovary or peritoneum, and it is characterised by extensive psammoma body formation and invasion of surrounding structures. This report describes the case of a 42-year-old woman who presented with large ascites and raised CA125 level. Following a full staging laparotomy, she was made stable in stage IIIC. Despite the limited number of cases reported, the clinical prognosis of carcinomas resembling the serous borderline lesions seems much more favourable than the common serous carcinomas. A summary of all the reported cases is provided to highlight the clinical and prognostic features of this scarce tumour. PMID:21686474
Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination
Miyoshi, Ai; Miyatake, Takashi; Hara, Takeya; Tanaka, Asuka; Komura, Naoko; Komiya, Shinnosuke; Kanao, Serika; Takeda, Masumi; Mimura, Mayuko; Nagamatsu, Masaaki; Yokoi, Takeshi
Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID:26858849
Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna
Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204
Oberascher, G; Albegger, K
Typical symptoms of the otitis media with effusion (OME)--synonym (secretory otitis media--SOM)--are fluid (serous/mucoid) in the middle ear space and a conductive hearing loss. Its most incidence can be found in infants and kids, during this period often bilaterally, but also in adolescents and adults. Etiopathological factors are infections of the upper respiratory tract, obstructing adenoids, tumors of the nasopharynx, cleft palate patients, allergological and immunological influences. As most important anatomical factor ventilation problems, respectively insufficiency of drainage of the eustachian tube is considered. Especially in childhood, OME reveals high spontaneous remission. Thus in many cases is no need for treatment. Persists OME over a longer period (some months) or in patients with recurrent disease, therapy is necessary: decongestant nasal drops, local heat during concomitant upper air way infections, long term application of low dose antibiotics, adenoidectomy with myringotomy, or insertion of ventilating tubes.
Buttarelli, Marianna; Mascilini, Floriana; Zannoni, Gian Franco; Ciucci, Alessandra; Martinelli, Enrica; Filippetti, Flavia; Scambia, Giovanni; Ferrandina, Gabriella; Gallo, Daniela
Low-grade serous ovarian carcinomas (LGSOCs) are a histological subtype of epithelial ovarian tumors, accounting for fewer than 5% of all cases of ovarian carcinoma. Due to the chemoresistant nature of this subtype a search for more effective systemic therapies is actively ongoing, hormonal therapy showing some degree of activity in this clinical setting. The present study ought to investigate the hormone receptor status of LGSOCs, as a strategy to provide molecular support for patient-tailored hormonal treatments. Estrogen receptor α (ERα), ERβ isoforms (i.e. ERβ1, ERβ2 and ERβ5), progesterone and androgen receptor (PR, AR) expression was evaluated by immunohistochemistry in 25 untreated LGSOC primary tumors, 6 matched metastases and 6 micropapillary variant of serous borderline tumors (micropapillary SBOTs). In vitro cellular models were used to provide insights into clinical observations. Our results showed prominent expression of nuclear ERα, ERβ2, ERβ5 and PR in LGSOC primary tissues, while metastatic lesions also exhibit considerable cytoplasmic ERβ2 levels. Notably, a higher expression of ERβ1 protein was determined in micropapillary SBOTs compared to LGSOCs. In vitro experiments on LGSOC cell lines (i.e. HOC-7 and VOA-1056) revealed low/absent ERα, PR and AR protein expression, whereas the three ERβ isoforms were all present. Proliferation of HOC-7 and VOA-1056 was not modulated by either the endogenous or the selective synthetic ligands. These novel findings highlight the need of assessing relative levels of ERα and ERβ isoforms in the total receptor pool in future clinical studies investigating molecular predictors of response to hormonal therapy in LGSOC. Copyright © 2017 Elsevier Inc. All rights reserved.
Chevalier, Nicolas; Paris, Françoise; Fontana, Sylvie; Delotte, Jérôme; Gaspari, Laura; Ferrari, Patricia; Sultan, Charles; Fénichel, Patrick
McCune-Albright syndrome (MAS), due to a somatic mutation of the GNAS1 gene, begins usually in girls with peripheral precocious puberty. Ovarian autonomy may persist in adulthood with acyclic hyperestrogenemia, infertility, and a potential risk of estrogen-dependent cancer. A 22-year-old woman, with MAS, was referred for infertility with left macropolycystic ovary, hyperestrogenemia, and chronic anovulation unsuccessfully treated by controlled hyperstimulation. Once ovarian cyst punctures and cDNA analysis verified that GNAS1 mutation was restricted to the left ovary, unilateral ovariectomy was performed. It improved right ovarian function, allowed an in vitro fertilization-induced pregnancy, but revealed an unexpected borderline epithelial ovarian tumor. Several breast cancers have already been reported in young MAS patients but not a borderline epithelial ovarian tumor. In this context, we would recommend that persistent hyperestrogenemia in an adult be corrected and gynecological follow-up of the breasts, ovaries, and endometrium be implemented. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
Nakamura, Kohei; Nakayama, Kentaro; Ishibashi, Tomoka; Ishikawa, Noriyoshi; Ishikawa, Masako; Katagiri, Hiroshi; Minamoto, Toshiko; Sato, Emi; Sanuki, Kaori; Yamashita, Hitomi; Iida, Kouji; Sultana, Razia; Kyo, Satoru
Ovarian low-grade serous carcinoma is thought to begin as a serous cystadenoma or adenofibroma that progresses in a slow stepwise fashion. Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression. This is the first report to track the histopathological progression of serous adenofibroma to low-grade serous carcinoma. Each stage was individually analyzed by pathological and molecular genetic methods to determine what differences occur between the distinct stages of progression.
Koncoro, Hendra; Putra, I Komang W D; Wibawa, I Dewa N
Macrocystic serous cystadenoma is an unusual and essentially benign pancreatic tumor. Herein, we report on a 40-year-old woman diagnosed with macrocystic serous cystadenoma who presented with obstructive jaundice. A cystic lesion in the head and body of the pancreas was revealed by abdominal computed tomography. Intraoperative pancreatic cyst aspiration ruled out mucinous cystic neoplasm which has a malignant potential. The pancreatic cyst fluid cytology was basophilic amorph materials concluded as benign cystic lesion. Internal drainage was performed instead of pancreatic resection which showed good outcome. Biliary obstruction is a rare complication of serous cystadenoma. This case describes an unusual clinical presentation of macrocystic serous cystadenoma.
Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk-Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, Andrzej
The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinico-pathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinico-pathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). We
Hecht, Jonathan L; Konstantinopoulos, Panagiotis A; Awtrey, Christopher S; Soslow, Robert A
Uterine serous carcinoma is a uncommon aggressive variant of endometrial cancer whose biologic origin is unclear. Mutations in p53 and BRCA1 genes play a key role in ovarian serous carcinogenesis. We investigated whether the loss of BRCA1 expression plays a similar role in uterine serous carcinoma. Loss of BRCA1 expression and Wilms tumor 1 (WT-1) overexpression were detected by immunohistochemical analysis. Depth of myometrial invasion, the presence of precursor lesions or polyps, and clinical parameters (age, history of breast cancer, and germline BRCA1 mutation status) were recorded. A total of 27 cases were available for evaluation. Three tumors (11.1%, 95% confidence interval, 2%-29%) showed the loss of BRCA1 expression. Two of these had known germline mutation in BRCA1, and the third had not been analyzed. Two of these cases expressed WT-1 or showed some morphologic features suggestive of drop metastasis from the adnexa, but no case showed detectable serous tubal intraepithelial carcinoma or features of an ovarian primary tumor. Overall, 5 women in the group had a personal history of breast cancer, and the finding was significantly associated with BRCA1 staining (P=0.049). A subset of uterine serous carcinomas shows the loss of BRCA1 protein and is associated with germline mutation.
Reid, Michelle D; Choi, Hyejeong; Balci, Serdar; Akkas, Gizem; Adsay, Volkan
We herein summarize the pathology and most recent advances in the molecular genetics of serous cystic neoplasms of the pancreas. They typically present as relatively large, well-demarcated tumors (mean size, 6cm), predominantly occurring in females. Pre-operative diagnosis remains challenging; imaging findings and cyst fluid analysis often prove non-specific and fine-needle aspiration often does not yield diagnostic cells. Pathologically, they are characterized by a distinctive cytology referred to as "serous." Although they have ductal differentiation, they distinctly lack the mucin production that characterizes most other pancreatic ductal tumors, including ductal adenocarcinoma and its variants, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). They instead produce abundant glycogen (glycogen-rich adenoma). Serous cystadenomas also lack the molecular alterations that characterize ductal neoplasms, such as mutation of KRAS (high prevalence in most mucinous ductal neoplasms), inactivation of SMAD4 (seen in ductal adenocarcinomas), and mutations in GNAS (seen in some IPMNs) and RNF43 (detected in MCNs and IPMNs). Instead, new molecular and immunohistochemical observations place serous pancreatic tumors closer to "clear cell neoplasms" seen in various other organs that are associated with the von Hippel-Lindau (VHL) pathway, such as clear cell renal cell carcinomas and capillary hemangioblastomas. Patients with VHL syndrome have an increased risk of developing serous pancreatic tumors and somatic mutations of the VHL gene are common in these tumors along with modification of its downstream effectors including hypoxia-inducible factor (HIF1), glucose uptake and transporter-1 (GLUT-1), a common factor in clear cell (glycogen-rich) tumors, as well as expression of vascular endothelial growth factor (VEGF), thought to be a factor in the striking capillarization of serous cystadenomas and other non-pancreatic clear cell tumors. VEGF may
Carlson, Joseph; Roh, Michael H.; Chang, Martin C.; Crum, Christopher P.
Summary In the past 50 years, the concept of serous ovarian cancer has been progressively refined, with the distinction of the borderline serous tumour, identification of a smaller subset of well-differentiated serous malignancies and, recently, closer attention to the pathogenesis of high-grade serous malignancies. High-grade serous carcinoma, traditionally presumed to arise within Müllerian inclusion cysts of the ovarian surface, cortex and peritoneum, has recently been linked to the distal fallopian tube. This review addresses the disparate forms of serous neoplasia, which reflect both different genetic abnormalities and stages of differentiation of Müllerian epithelium. The significance of these different origins is addressed in the context of ovarian cancer prevention. PMID:20953242
Morana, Giovanni; Guarise, Alessandro
Cystic tumors of the pancreas are less frequent than solid lesions and are often detected incidentally, as many of these lesions are small and asymptomatic. However, they may be associated with pancreatitis or have malignant potential. With advancements in diagnostic imaging, cystic lesions of the pancreas are being detected with increasing frequency. Many lesions can cause a pancreatic cyst, most being non-neoplastic while approximately 10% are cystic tumors, ranging from benign to highly malignant tumors. With increasing experience it is becoming clear that the prevalence of pseudocyst among cystic lesions of the pancreas is lower than usually presumed. A presumptive diagnosis of pseudocyst based on imaging appearance alone can cause a diagnostic error, and neoplastic cysts of the pancreas are particularly susceptible to this misdiagnosis, which can result in inappropriate treatment. Cystic tumors of the pancreas are formed by serous or mucinous structures showing all stages of cellular differentiation. According to the WHO classification, they can be subdivided on the basis of their histological type and biological behavior into benign tumors, borderline tumors, and malignant tumors. Cystic pancreatic tumors can be subdivided into peripheral (serous cystadenomas, mucinous cystic tumors, solid and papillary epithelial neoplasms, cystic islet cell tumors), which do not communicate with the main pancreatic duct, and ductal tumors (mucinous tumor), according to their site of origin. On the basis of imaging criteria alone, it can be very difficult to differentiate non-tumoral cystic lesions from neoplastic ones. The management of these patients is complex, and it is important to correlate imaging findings with knowledge of the patient’s symptoms and of the natural history and predictors of malignancy in pancreatic cysts. PMID:16861136
Yahata, Tetsuro; Banzai, Chiaki; Tanaka, Kenichi
The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan. Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007. A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid adenocarcinoma showed a steady increasing trend, and those of clear cell and mucinous adenocarcinomas showed significant increasing trends in the total population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in the 50+ age group were significantly increased, especially the incidence of clear cell adenocarcinoma, which strikingly increased by approximately threefold from 1.2 (1983-1989) to 3.5 (2000-2007) per 100,000 females. This prefecture-wide study showed the practical trends in ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.
Hosford, S; Elliott, J; Ma, Z-W; Majeste, R; Dubeshter, B
The objective of this paper is to evaluate the relationship between CD44 expression and the clinicopathologic features of papillary serous endometrial cancer. CD44 expression was assessed in 32 cases of papillary serous endometrial carcinoma by standard immunohistochemical staining techniques. Clinicopathologic features including myometrial invasion, nodal metastases, tumor spread, stage, and the shedding of malignant cells on cervical cytology were reviewed. The Chi-square test was used for statistical analysis. CD44 was not expressed in 81% of patients with papillary serous endometrial carcinoma. Malignant cells were seen on cervical cytology in 68% of all cases with significantly more in the CD44-negative group (78% vs. 33%, P 0.05). CD44 expression was not related to stage, myometrial invasion, nodal involvement, or intraperitoneal spread. We conclude that the cell adhesion molecule CD44 is expressed infrequently in papillary serous endometrial carcinoma. Shedding of malignant cells on cervical cytology is common in papillary serous endometrial cancer and occurs more frequently in CD44-negative cases. CD44 expression doesn't appear to be related to known prognostic features such as nodal metastases or stage. The biologic aggressiveness of this tumor type may, in part, be related to its lack of CD44 expression.
Liang, Li; Jiang, Yi; Chen, Jun-Song; Niu, Na; Piao, Jin; Ning, Jing; Zu, Youli; Zhang, Jing; Liu, Jinsong
The B7 family of immune costimulatory ligands is a group of cell surface proteins that bind to the surface receptors of lymphocytes to fine-tune immune responses. The aberrant expression of these proteins plays a key role in tumor immune evasion. Immunotherapy targeting certain B7 family members, including programmed death ligand 1, has proven quite effective in suppressing tumor growth. However, why such therapy works in only a subgroup of tumors is unclear. We hypothesized that other B7 family members, either alone or in concert with programmed death ligand 1, play a crucial role in tumor pathogenesis and progression. We therefore examined the expression of a newly discovered B7 family member, B7-H4, in 306 cases of ovarian serous carcinoma by immunohistochemistry. We found that 91% (267/293) of the high-grade ovarian serous carcinomas and 69% (9/13) of the low-grade ovarian serous carcinomas expressed B7-H4. The difference between B7-H4 expression in high-grade and low-grade ovarian serous carcinoma was statistically significant (P=.002). Moreover, B7-H4 protein expression in high-grade serous carcinoma was associated with tumor stage (P<.01) but not overall survival or disease-free survival. In conclusion, B7-H4 is frequently expressed in ovarian serous carcinomas, especially high-grade serous carcinomas, and may represent a novel immunotherapeutic target in this cancer.
Kuhn, Elisabetta; Bahadirli-Talbott, Asli; Shih, Ie-Ming
Uterine serous carcinoma accounts for only 10% of all uterine epithelial cancers, but is the leading cause of death among them. The pathogenesis of this aggressive neoplasm has been largely elusive until recently, when comprehensive genome-wide analyses of uterine serous carcinoma have been performed. Among amplified cancer-related genes, CCNE1, encoding for cyclin E1, is frequently amplified in uterine serous carcinoma. In the current study we applied fluorescence in situ hybridization (FISH) to determine CCNE1 copy number in uterine serous carcinoma and concurrent endometrial intraepithelial carcinoma, the noninvasive component of uterine serous carcinoma, and the results were correlated with clinicopathological and molecular features. We found that 20 (45%) of 44 uterine serous carcinomas and 11 (41%) of 27 endometrial intraepithelial carcinomas showed CCNE1 amplification. Overall, we found high concordance in CCNE1 copy number in concurrent uterine serous carcinoma and endometrial intraepithelial carcinoma pairs (P-value=0.0003). No correlation was observed between CCNE1 copy number and clinicopathological features, as well as common mutations previously reported in uterine serous carcinoma. In summary, we confirm that amplification of CCNE1 is a frequent molecular genetic change in uterine serous carcinoma. Moreover, the identification of CCNE1 amplification in many endometrial intraepithelial carcinomas suggests that this genetic event occurs early during tumor progression.
AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem
Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523
Ren, Caixia; Du, Juan; Xi, Chenguang; Yu, Yu; Hu, Ajin; Zhan, Jun; Guo, Hongyan; Fang, Weigang; Liu, Congrong; Zhang, Hongquan
Kindlin-2 has been known to promote most cancer progression through regulation of multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2 was identified in serous epithelial ovarian cancer progression, which sharply contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic low expression of Kindlin-2 was found in the tumor tissues of serous epithelial ovarian cancer, especially in the high-grade serous epithelial ovarian cancer. Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression correlated with higher tumor grade and older patients. Intriguingly, decreased Kindlin-2 expression predicts poor overall and progression-free survivals in serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a mesenchymal to epithelial transition in serous epithelial ovarian cancer cells, at least in part, by up-regulation of estrogen receptor α which was recruited to the promoter of E-cadherin and thereby enhanced the transcription of E-cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients.
Oosterhuis, J A
To study the familial occurrence of central serous retinopathy (CSR). We pooled data from eight eye clinics in Western Europe. We collected 11 families that each had two to four members with CSR. In 10 families siblings and in one family a mother and son were affected. Sixty percent of the patients were male and 40% female. CSR was found in 55 (92%) of 60 eyes, 44 (80%) showing a chronic course. In 25 patients (83%) both eyes were affected. Most recent visual acuity was 0.5 or less in 17 (39%) and 0.2 or less in 8 (18%) of the eyes with chronic CSR. Our findings of familial occurrence and a chronic disorder that is progressive, diffuse, and bilateral suggest an inborn disposition to develop a clinically manifest disintegration of the retinal pigment epithelium in adulthood.
Ono, Kyoko; Hayashi, Hiroyuki; Tateno, Masatoshi; Tanaka, Reiko; Suzuki, Rie; Maruyama, Yasuyo; Miyagi, Yohei; Furuya, Mitsuko
Uterine superficial serous carcinoma (SSC) and serous endometrial intraepithelial carcinoma (SEIC) are unique malignancies found primarily in postmenopausal women. SSC and SEIC lesions measuring 1 cm or less are categorized as minimal uterine serous carcinoma (MUSC). Less well understood, however, the clinical behavior of SSC and SEIC lesions measuring more than 1 cm. We investigated 6 postmenopausal patients, aged 69-83 years, with SSC or SEIC and without hyperestrogenism. All but 1 patient had tumors originating from the surface of polyps, including 3 patients who each had an enormous polyp occupying the entire uterine cavity. Two patients had extensive SEICs measuring more than 1 cm; the others had SSCs, including 1 MUSC. The mesenchymal cells of the cancer-bearing polyps lacked the morphologic characteristics of endometrial stroma, and the cancer glands often immunostained negatively for estrogen receptors and progesterone receptors. Diffuse immunostaining for human epidermal growth factor receptor 2 was detected in 3 patients, and p53 was detected in all. Cyclin E, a downstream molecule of the F-box and WD repeat domain-containing 7 (FBXW7), was detected in all patients. Microdissected cancer glands showed p53 mutations in 2 patients and a FBXW7 mutation in 1 patient. These findings suggest that mutations of FBXW7 and p53 may contribute to the carcinogenesis of less invasive tumor subtypes. Pathologists and physicians should carefully evaluate SSC and SEIC lesions involving large polyps but lacking myometrial invasion.
Cesaratto, Laura; Grisard, Eleonora; Coan, Michela; Zandonà, Luigi; De Mattia, Elena; Poletto, Elena; Cecchin, Erika; Puglisi, Fabio; Canzonieri, Vincenzo; Mucignat, Maria Teresa; Zucchetto, Antonella; Stocco, Gabriele; Colombatti, Alfonso; Nicoloso, Milena S; Spizzo, Riccardo
Rs3814113 is the single-nucleotide polymorphism (SNP) showing the strongest association with high-grade serous ovarian carcinoma (HGSOC) incidence and is located in an intergenic region about 44 kb downstream of basonuclin 2 (BNC2) gene. Lifetime number of ovulations is associated with increased risk to develop HGSOC, probably because of cell damage of extrauterine Müllerian epithelium by ovulation-induced oxidative stress. However, the impact of low-penetrance HGSOC risk alleles (e.g. rs3814113) on the damage induced by oxidative stress remains unclear. Therefore, the purpose of this study was to investigate whether rs3814113 genetic interval regulates BNC2 expression and whether BNC2 expression levels impact on cell survival after oxidative stress. To do this, we analyzed gene expression levels of BNC2 first in HGSOC data sets and then in an isogenic cell line that we engineered to carry a 5 kb deletion around rs3814113. Finally, we silenced BNC2 and measured surviving cells after hydrogen peroxide (H2O2) treatment to simulate oxidative stress after ovulation. In this paper, we describe that BNC2 expression levels are reduced in HGSOC samples compared with control samples, and that BNC2 expression levels decrease following oxidative stress and ovulation in vitro and in vivo, respectively. Moreover, deletion of 5 kb surrounding rs3814113 decreases BNC2 expression levels in an isogenic cell line, and silencing of BNC2 expression levels increases cell survival after H2O2 treatment. Altogether, our findings suggest that the intergenic region located around rs3814113 regulates BNC2 expression, which in turn affects cell survival after oxidative stress response. Indeed, HGSOC samples present lower BNC2 expression levels that probably, in the initial phases of oncogenic transformation, conferred resistance to oxidative stress and ultimately reduced the clearance of cells with oxidative-induced damages.
Izadi-Mood, Narges; Samadi, Nasrin; Sarmadi, Soheila; Eftekhar, Zahra
Adenocarcinoma arising from adenomyosis uteri is rare. Herein, we reported a patient with papillary serous carcinoma arising from adenomyosis. The patient was a 61-year-old woman who received tamoxifen for treatment of her breast cancer over the past five years. In hysterectomy specimen taken for investigating her uncontrolled bleeding with suspicion of uterine myoma, multiple adenomyotic foci were found in the uterine wall. In one of these foci, papillary serous carcinoma was found. No evidence of tumor was seen in endometrial surface, peritoneum, and both adnexa.
Akeson, M; Zetterqvist, B-M; Dahllöf, K; Jakobsen, A-M; Brännström, M; Horvath, G
Borderline ovarian tumors (BOTs) make up around 10-20% of all epithelial ovarian tumors. The aim of the present study was to investigate the outcome of a complete large population-based cohort of patients treated for BOT. All patients (n= 399) treated for BOT in the western part of Sweden (population around 1.6 million) between 1993 and 2004 were followed. The treatment consisted of primary staging surgery with addition of platinum-based adjuvant chemotherapy for the majority of aneuploid tumors. Data relating to the surgical procedure, FIGO stage, histopathology, ploidy status, adjuvant chemotherapy, and disease state (recurrence or death) at follow-up visits were continuously entered into a cancer quality registry. Data concerning cases and deaths were also controlled against the Swedish National Cancer Registry. The median age of the BOT patients was 55 years (range 16-90). The relative 5- and 10-year survivals were 99.9% (95% CI 96.3-102.4) and 103.5% (95% CI 97.2-108.2), respectively. Aneuploidy was found in 63 (17%) patients, with significantly more aneuploid tumors found among patients of older (>60 years) age. Out of the 399 patients, 8 had recurrence of the disease. Three of the eight patients died from the disease. Five patients with recurrence are alive, three of these patients with no signs of disease after additional treatment. This complete long-term follow-up of a large population-based cohort of BOT patients shows that there is a good overall survival in this patient group.
Grisham, Rachel N.; Sylvester, Brooke E.; Won, Helen; McDermott, Gregory; DeLair, Deborah; Ramirez, Ricardo; Yao, Zhan; Shen, Ronglai; Dao, Fanny; Bogomolniy, Faina; Makker, Vicky; Sala, Evis; Soumerai, Tara E.; Hyman, David M.; Socci, Nicholas D.; Viale, Agnes; Gershenson, David M.; Farley, John; Levine, Douglas A.; Rosen, Neal; Berger, Michael F.; Spriggs, David R.; Aghajanian, Carol A.; Solit, David B.; Iyer, Gopa
Purpose No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Patients and Methods Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Results Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor–based combination therapy. Conclusion Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional
Kakkar, Aanchal; Sharma, Mehar C; Yadav, Rajni; Panwar, Rajesh; Mathur, Sandeep R; Iyer, Venkateswaran K; Sahni, Peush
Mixed serous neuroendocrine neoplasms are extremely rare tumors that are usually seen in female patients and are often associated with von Hippel Lindau (VHL) disease. We describe the case of a 38-year-old male who presented with complaints of anorexia, weight loss, and abdominal pain. CT abdomen showed a mass in the head of the pancreas, multiple small nodules in the body of pancreas, and bilateral adrenal masses. Fine needle aspiration cytology (FNAC) from the mass showed features of a neuroendocrine tumor, with many of the cells demonstrating abundant clear cytoplasm. Histopathological examination of the pancreaticoduodenectomy specimen showed a mixed serous neuroendocrine neoplasm with two components viz. serous cystadenoma and neuroendocrine tumor (NET) World Health Organization (WHO) grade 2. In addition, he was diagnosed to have bilateral pheochromocytomas and a paraganglioma. The synchronicity of these tumors suggested the possibility of VHL disease. Thus, identification of a NET with clear cells or of a mixed serous neuroendocrine neoplasm should raise suspicion of VHL disease. In a mixed tumor, FNAC may identify only one of the two components. Thorough processing of all pancreatic serous tumors for pathological examination is recommended, as NET may occur as a small nodule within the serous cystadenoma.
Vang, Russell; Levine, Douglas A; Soslow, Robert A; Zaloudek, Charles; Shih, Ie-Ming; Kurman, Robert J
The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the
Aust, Stefanie; Felix, Sophie; Auer, Katharina; Bachmayr-Heyda, Anna; Kenner, Lukas; Dekan, Sabine; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Pils, Dietmar
Immune-evasion and immune checkpoints are promising new therapeutic targets for several cancer entities. In ovarian cancer, the clinical role of programmed cell death receptor ligand 1 (PD-L1) expression as mechanism to escape immune recognition has not been clarified yet. We analyzed PD-L1 expression of primary ovarian and peritoneal tumor tissues together with several other parameters (whole transcriptomes of isolated tumor cells, local and systemic immune cells, systemic cytokines and metabolites) and compared PD-L1 expression between primary tumor and tumor recurrences. All expressed major histocompatibility complex (MHC) I genes were negatively correlated to PD-L1 abundances on tumor tissues, indicating two mutually exclusive immune-evasion mechanisms in ovarian cancer: either down-regulation of T-cell mediated immunity by PD-L1 expression or silencing of self-antigen presentation by down-regulation of the MHC I complex. In our cohort and in most of published evidences in ovarian cancer, low PD-L1 expression is associated with unfavorable outcome. Differences in immune cell populations, cytokines, and metabolites strengthen this picture and suggest the existence of concurrent pathways for progression of this disease. Furthermore, recurrences showed significantly increased PD-L1 expression compared to the primary tumors, supporting trials of checkpoint inhibition in the recurrent setting. PMID:28266500
Background Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. Objective The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Methods Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. Results There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Conclusions Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants. PMID:24872845
Braicu, Elena Ioana; Van Gorp, Toon; Nassir, Mani; Richter, Rolf; Chekerov, Radoslav; Gasimli, Khayal; Timmerman, Dirk; Vergote, Ignace; Sehouli, Jalid
Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.
Hyman, David M.; Long, Kara C.; Tanner, Edward J.; Grisham, Rachel N.; Arnold, Angela G.; Bhatia, Jasmine; Phillips, Mary F.; Spriggs, David R.; Soslow, Robert A.; Kauff, Noah D.; Levine, Douglas A.
Objective BRCA-associated and sporadic ovarian cancers have different pathologic and clinical features. Our goal was to determine if BRCA mutation status is an independent predictor of residual tumor volume following primary surgical cytoreduction. Methods We conducted a retrospective analysis of patients with FIGO stage IIIC-IV high-grade serous ovarian cancer classified for the presence or absence of germline BRCA mutations. The primary outcome was tumor-debulking status categorized as complete gross resection (0mm), optimal but visible disease (1-10mm), or suboptimal debulking (>10mm) following primary surgical cytoreduction. Overall survival by residual tumor size and BRCA status was also assessed as a secondary endpoint. Results Data from 367 patients (69 BRCA mutated, 298 BRCA wild-type) were analyzed. Rate of optimal tumor debulking (0-10mm) in BRCA wild-type and BRCA-mutated patients were 70.1% and 84.1%, respectively (P=0.02). On univariate analysis, increasing age (10-year OR, 1.33; 95% CI, 1.07–1.65; P=0.01) and wild-type BRCA status (OR, 0.47; 95% CI, 0.23–0.94, P=0.03) were both significantly associated with suboptimal surgical outcome. On multivariate analysis, BRCA mutation status was no longer associated with residual tumor volume (OR, 0.63; 95% CI, 0.31–1.29; P=0.21) while age remained a borderline significant predictor (10-year OR, 1.25; 95% CI,1.01–1.56; P=0.05). Both smaller residual tumor volume and mutant BRCA status were significantly associated with improved overall survival. Conclusion BRCA mutation status is not associated with the rate of optimal tumor debulking at primary surgery after accounting for differences in patient age. Improved survival of BRCA carriers is not the result of better surgical outcomes but instead intrinsic tumor biology. PMID:22579790
Kohn, Elise C; Ivy, S Percy
Our understanding of epithelial ovarian cancer has blossomed, and we now recognize that it is a collection of varied histologic and molecularly different malignancies, many of which may not derive from a true ovarian anatomic precursor. High-grade serous ovarian cancer (HGSOC) is a unique type of epithelial cancer. It is characterized by nearly universal mutation in and dysfunction of p53, genomic instability rather than driver mutations, advanced stage at onset, and probable fallopian tube epithelium origin, with a serous tubal in situ carcinoma precursor. Germline deleterious mutations in BRCA1 and BRCA2, as well as other less prevalent genes involved in DNA repair, such as PALB2 and RAD51c, are associated with its carcinogenesis and may predict susceptibility to classes of treatment agents, including DNA-damaging agents and DNA repair inhibitors. Loss of function of these genes is associated with homologous recombination dysfunction (HRD). It is now recognized that there may be HGSOC with wild-type BRCA1 and BRCA2 with an identifiable HRD phenotype. Such HRD tumors also may be more susceptible to certain classes of treatments and may be phenotypically detectable with a composite molecular biomarker that has been shown to be predictive for response to PARP inhibitors. Use of this new knowledge of the anatomic and molecular background of HGSOC has led to the rational design of novel combinations of treatment classes to create an HRD-like cellular environment and thus drive treatment benefits.
Hedley, Catherine; Sriraksa, Ruethairat; Showeil, Rania; Van Noorden, Susan; El-Bahrawy, Mona
Serous endometrial carcinoma is an aggressive type of endometrial carcinoma. Wilms tumor gene 1 (WT-1) is commonly expressed in ovarian serous carcinomas and considered a diagnostic marker of these tumors. However, it is generally believed that WT-1 is rarely expressed by endometrial serous carcinoma. The aim of this study was to evaluate the frequency and significance of WT-1 expression in endometrial serous carcinoma. We studied the expression of WT-1 in formalin-fixed, paraffin-embedded tumor sections from 77 cases of endometrial serous carcinoma. Thirty-four tumors showed positive expression for WT-1 (44%). There was a statistically significant association between the presence of WT-1 expression and disease-free survival (DFS), where patients with tumors expressing WT-1 had a shorter DFS compared with those with no WT-1 expression (P = .031; median DFS, 15 and 38 months, respectively). By multivariate Cox regression analysis, DFS was independent from other clinicopathological data (tumor stage, presence of lymphovascular space invasion, cervical involvement, and extrauterine spread), indicating that WT-1 expression is independently associated with DFS. Our study shows that WT-1 is expressed in a considerable percentage of endometrial serous carcinomas, suggesting a role for WT-1 in the pathology of these tumors. This has therapeutic significance, as WT-1 is an emerging target for immunotherapy. Moreover, our results show that WT-1 has prognostic value, being predictive of DFS. As a potential prognostic marker and therapeutic target, we recommend that WT-1 expression should be included in histopathologic reports of endometrial serous carcinoma.
E. Burdette 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:email@example.com 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS...explain the presence of tumor mass in the ovary of serous patients. 3D ovarian organ culture conditioned medium will be used as the chemoattractant...changes responsible for adhesion on collagen. Ovarian conditioned medium (OCM) with and without H2O2 treatment will be added to normal and our series of
Kainuma, Osamu; Yamamoto, Hiroshi; Cho, Akihiro; Arimitsu, Hidehito; Yanagibashi, Hiroo; Takiguchi, Nobuhiro; Nabeya, Yoshihiro; Kawana, Hidetada
Serous cystic neoplasms (SCN) of the pancreas are typically honeycombed microcystic masses, which are believed to be benign entity. This report describes a case of a 69-year-old man with a rare solid type of serous cystadenocarcinoma of the pancreas with liver metastases. A 6-cm well enhanced pancreatic tumor and multiple liver nodules were depicted with contrast medium on computed tomography scan. Distal pancreatectomy was performed at first operation. The cut surface of the tumor was solid and glossy appearance. Second operation of liver resection for all metastatic nodules was performed 27 months after the initial operation. The tumor cells in both the pancreas and the liver had cytoplasmic periodic acid-Schiff positive granules, which were completely digested by diastase. Eleven cases of serous cystadenocarcinoma of the pancreas have been reported in the literature. To our knowledge, this is the first case of a solid type serous cystadenocarcinoma.
Fadare, Oluwole; Roma, Andres A; Parkash, Vinita; Zheng, Wenxin; Walavalkar, Vighnesh
An aberrant p53 immunophenotype may be identified in several histotypes of endometrial carcinoma, and is accordingly recognized to lack diagnostic specificity in and of itself. However, based on the high frequency with which p53 aberrations have historically been identified in endometrial serous carcinoma, a mutation-type immunophenotype is considered to be highly sensitive for the histotype. Using an illustrative case study and a review of the literature, we explore a relatively routine diagnostic question: whether the negative predictive value of a wild-type p53 immunophenotype for serous carcinoma is absolute, that is, whether a p53-wild type immunophenotype is absolutely incompatible with a diagnosis of serous carcinoma. The case is an advanced stage endometrial carcinoma that was reproducibly classified by pathologists from 3 institutions as serous carcinoma based on its morphologic features. By immunohistochemistry, the tumor was p53-wild type (DO-7 clone), diffusely positive for p16 (block positivity), and showed retained expression of PTEN, MSH2, MSH6, MLH1, and PMS2. Next generation sequencing showed that there indeed was an underlying mutation in TP53 (D393fs*78, R213*). The tumor was microsatellite stable, had a low mutational burden (4 mutations per MB), and displayed no mutations in the exonuclease domain of DNA polymerase epsilon (POLE) gene. Other genomic alterations included RB1 mutation (R46fs*19), amplifications in MYST3 and CRKL, and ARID1A deletion (splice site 5125-94_5138del108). A review of the recent literature identified 5 studies in which a total of 259 cases of serous carcinoma were whole-exome sequenced. The average TP53 mutational rate in endometrial serous carcinoma was only 75% (range, 60 to 88). A total of 12 (33%) of 36 immunohistochemical studies reported a p53-aberrant rate of <80% in endometrial serous carcinoma. We discuss in detail several potential explanations that may underlie the scenario of serous carcinoma-like morphology
Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli
Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.
Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli
Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166
Zeppernick, Felix; Meinhold-Heerlein, Ivo; Shih, Ie-Ming
Ovarian tumors comprise a wide variety of entities. The largest group, epithelial ovarian carcinoma, can be classified into two main groups, type I and type II tumors. Recent advances in the understanding of ovarian cancer development have resulted in the finding of ‘serous tubal intraepithelial carcinoma’, which is believed to represent the precursor lesion in high-grade serous ovarian carcinoma. In this review, lines of evidence for this are discussed and possible future implications for clinical and research settings are outlined. PMID:25330822
Brown, Patrick O.; Palmer, Chana
Background Ovarian cancer kills approximately 15,000 women in the United States every year, and more than 140,000 women worldwide. Most deaths from ovarian cancer are caused by tumors of the serous histological type, which are rarely diagnosed before the cancer has spread. Rational design of a potentially life-saving early detection and intervention strategy requires understanding the lesions we must detect in order to prevent lethal progression. Little is known about the natural history of lethal serous ovarian cancers before they become clinically apparent. We can learn about this occult period by studying the unsuspected serous cancers that are discovered in a small fraction of apparently healthy women who undergo prophylactic bilateral salpingo-oophorectomy (PBSO). Methods and Findings We developed models for the growth, progression, and detection of occult serous cancers on the basis of a comprehensive analysis of published data on serous cancers discovered by PBSO in BRCA1 mutation carriers. Our analysis yielded several critical insights into the early natural history of serous ovarian cancer. First, these cancers spend on average more than 4 y as in situ, stage I, or stage II cancers and approximately 1 y as stage III or IV cancers before they become clinically apparent. Second, for most of the occult period, serous cancers are less than 1 cm in diameter, and not visible on gross examination of the ovaries and Fallopian tubes. Third, the median diameter of a serous ovarian cancer when it progresses to an advanced stage (stage III or IV) is about 3 cm. Fourth, to achieve 50% sensitivity in detecting tumors before they advance to stage III, an annual screen would need to detect tumors of 1.3 cm in diameter; 80% detection sensitivity would require detecting tumors less than 0.4 cm in diameter. Fifth, to achieve a 50% reduction in serous ovarian cancer mortality with an annual screen, a test would need to detect tumors of 0.5 cm in diameter. Conclusions Our
Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma
Zang, Xingxing; Sullivan, Peggy S; Soslow, Robert A; Waitz, Rebecca; Reuter, Victor E; Wilton, Andrew; Thaler, Howard T; Arul, Manonmani; Slovin, Susan F; Wei, Joyce; Spriggs, David R; Dupont, Jakob; Allison, James P
B7-H3 and B7x are members of the B7 family of immune regulatory ligands that are thought to attenuate peripheral immune responses through co-inhibition. Previous studies have correlated their overexpression with poor prognosis and decreased tumor-infiltrating lymphocytes in various carcinomas including uterine endometrioid carcinomas, and mounting evidence supports an immuno-inhibitory role in ovarian cancer prognosis. We sought to examine the expression of B7-H3 and B7x in 103 ovarian borderline tumors and carcinomas and study associations with clinical outcome. Using immunohistochemical tissue microarray analysis on tumor specimens, we found that 93 and 100% of these ovarian tumors express B7-H3 and B7x, respectively, with expression found predominantly on cell membranes and in cytoplasm. In contrast, only scattered B7-H3- and B7x-positive cells were detected in non-neoplastic ovarian tissues. B7-H3 was also expressed in the endothelium of tumor-associated vasculature in 44% of patients, including 78% of patients with high-stage tumors (FIGO stages III and IV), nearly all of which were high-grade serous carcinomas, and 26% of patients with low-stage tumors (FIGO stages I and II; P<0.001), including borderline tumors. Analysis of cumulative survival time and recurrence incidence revealed that carcinomas with B7-H3-positive tumor vasculature were associated with a significantly shorter survival time (P=0.02) and a higher incidence of recurrence (P=0.03). The association between B7-H3-positive tumor vasculature and poor clinical outcome remained significant even when the analysis was limited to the high-stage subgroup. These results show that ovarian borderline tumors and carcinomas aberrantly express B7-H3 and B7x, and that B7-H3-positive tumor vasculature is associated with high-grade serous histological subtype, increased recurrence and reduced survival. B7-H3 expression in tumor vasculature may be a reflection of tumor aggressiveness and has diagnostic and
Moore, Patrick S.; Zamboni, Giuseppe; Brighenti, Antonietta; Lissandrini, Daniele; Antonello, Davide; Capelli, Paola; Rigaud, Gildas; Falconi, Massimo; Scarpa, Aldo
Pancreatic serous microcystic adenomas (SCAs) are rare, benign tumors with a striking female preference. Virtually no information is available about chromosomal or genetic anomalies in this disease. We performed extensive molecular characterization of 21 cases of formalin-fixed, paraffin-embedded sporadic SCAs consisting in genome-wide allelic loss analysis with 79 microsatellite markers covering all 22 autosomes, assessment of microsatellite instability, and mutational analysis of the VHL, K-ras, and p53 genes in nine cases for which frozen tissue was available. Although no case showed microsatellite instability of the type seen in mismatch repair-deficient tumors, a relatively low fractional allelic loss of 0.08 was found. Losses on chromosome 10q were the most frequent event in SCAs (50% of cases), followed by allelic losses on chromosome 3p (40% of cases). Moderately frequent losses (>25% of cases) were found on chromosomes 1q, 2q, and 7q. The VHL gene, located on chromosome 3p, had somatic inactivating mutations in two of nine cases (22%), whereas no mutations were found in either K-ras or p53, in agreement with the finding that all 21 cases stained negative for p53 by immunohistochemistry. Our study indicates that the involvement of chromosomal arms 10q and 3p is characteristic of SCAs and that the VHL gene is involved in a subset of sporadic cases. PMID:11141506
Enomoto, T.; Weghorst, C. M.; Inoue, M.; Tanizawa, O.; Rice, J. M.
To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031). Images Figure 1 Figure 2 PMID:1656759
Being on the borderline as a student in higher education is not always negative, to do with marginalisation, exclusion and having a voice that is vulnerable. Paradoxically, being on the edge also has positive connections with integration, inclusion and having a voice that is strong. Alternative understandings of the concept of borderline space can…
Being on the borderline as a student in higher education is not always negative, to do with marginalisation, exclusion and having a voice that is vulnerable. Paradoxically, being on the edge also has positive connections with integration, inclusion and having a voice that is strong. Alternative understandings of the concept of borderline space can…
Brandone, Nicolas; Poizat, Flora; Thomassin-Piana, Jeanne; Turrini, Olivier; Popovici, Cornel; Terris, Benoît
Cystic pancreatic neoplasms concern 1 to 2% of the pancreatic tumours. The serous ones are considered benign tumours but since 1989, several pancreatic serous cystadenocarcinomas (SCAC) cases have been reported. We report the case of a SCAC with a particular pattern. An 80-year-old female patient presented a 4-cm tumour in the neck of the pancreas associated with liver lesions evoking, on imagery exams, focal nodular hyperplasia nests. A cephalic duodenopancreatectomy and a resection of the liver lesions were carried out. The gross exam showed a tumour with a pattern mostly solid and an area made of cysts. The microscopic exam displayed two patterns: the solid one, predominant, made of mild atypical clear cells, and the cystic one. The liver lesions revealed solid pattern similar to the pancreatic tumour one. The tumoral cells were cytokeratin 7, AE1/AE3 and inhibin positives. The Periodic-acid Schiff showed cytoplasmic granulations, which were digested after diasatasis. Only the presence of metastases allows distinguishing a pancreatic serous cystadenoma from a SCAC. To date, thirty cases of pancreatic SCAC have been reported. Immunohistochemistry cannot confirm the malignancy nature of the lesion but it needs to be done in order to cross out the differential diagnosis, that is pancreatic metastatic clear cell renal carcinoma. Nevertheless, it remains a pathology with good prognosis. Only two cases have been reported but ours case a predominant solid pattern.
Romero, Ignacio; Sun, Charlotte C; Wong, Kwong K; Bast, Robert C; Gershenson, David M
For the past several years, all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance leading to separate clinical trials for patients with this subtype originating from the Gynecologic Oncology Group's Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20-40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare - about 5%. Primary treatment of low-grade serous carcinoma includes surgery+platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonged overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormonal therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations. Copyright © 2013 Elsevier Inc. All rights reserved.
Saglam, Ozlen; Xiong, Yin; Marchion, Douglas C; Strosberg, Carolina; Wenham, Robert M; Johnson, Joseph J; Saeed-Vafa, Daryoush; Cubitt, Christopher; Hakam, Ardeshir; Magliocco, Anthony M
Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories. Category frequencies were compared between tumor specimens vs controls using an unpaired t test. Among tumors, category frequencies were compared between CR and IR to chemotherapy. Overall survival (OS) was stratified by category. In total, 74 ovarian serous carcinoma samples (32 CRs and 42 IRs), 28 normal controls, and 16 ovarian cancer cell lines were evaluable. High-level ERBB4 expression was observed at a significantly higher frequency in ovarian serous carcinoma compared with normal control tissue. Among tumor specimens, ERBB4 expression was significantly higher for those with an IR to chemotherapy compared with CR (P = .033). OS was inversely correlated with ERBB4 expression levels. Median rates of OS were 18, 22, and 58 months among high-, intermediate-, and low-expression tumors, respectively. Our results indicate that ERBB4 expression by immunohistochemistry may correlate with chemotherapy-resistant ovarian serous carcinoma and shortened OS.
Mingels, Marjanka J J M; van Ham, Maaike A P C; de Kievit, Ineke M; Snijders, Marc P M L; van Tilborg, Angela A G; Bulten, Johan; Massuger, Leon F A G
Serous ovarian cancer is suggested to develop from epithelium embryologically derived from the Müllerian ducts. The aim of the current study is to thoroughly, analyze the epithelium derived from the Müllerian ducts (cervix, endometrium and fallopian tubes) in serous ovarian cancer patients. Sixty women diagnosed with serous ovarian carcinoma were included in this multicentre, observational study. Tissues were embedded completely for histological assessment, in accordance with the SEE-Fim and SEE-End protocol (Sectioning and Extensively Examining of the Fimbriated end; and-Endometrium), and prevalence of cervical, as well as endometrial and tubal pathology was analyzed. In 31 (52%) cases, a pathologic lesion was identified, and in 16 (27%) of these cases coexistence of pathologic lesions. In 1 case, severe dysplasia was found in the cervix, in 9 (15%) cases endometrial intraepithelial carcinoma, in 19 (32%) cases atypical hyperplasia, and in 23 (43%) cases serous tubal intraepithelial carcinoma. Serous tubal intraepithelial carcinoma was seen significantly more often concurrent with endometrial atypical hyperplasia or endometrial intraepithelial carcinoma than with benign endometrium (64 vs 28%; P=0.01). To conclude, histological assessment of epithelium derived from Müllerian ducts of serous ovarian cancer patients resulted in the identification of endometrial intraepithelial carcinoma, serous tubal intraepithelial carcinoma and/or endometrial atypical hyperplasia in more than half of cases. Coexistence of these pathologic lesions was common, and might represent an effect of field carcinogenesis or tumor implantation of migrating cells.
Lee, Allie; Lai, Timothy Y Y
To report a case of central serous chorioretinopathy after solar eclipse viewing. A middle-age man developed a sudden-onset unilateral scotoma after viewing a partial solar eclipse in Hong Kong. Fundus examination, fluorescein angiography, and optical coherence tomography showed features compatible with central serous chorioretinopathy. The patient was managed conservatively and reevaluated periodically. Serial optical coherence tomographic evaluations demonstrated an initial increase in the amount of subretinal fluid which spontaneously resolved 10 weeks after the onset of symptoms. This case demonstrates the possibility of development of central serous chorioretinopathy following solar eclipse viewing.
Lee, Allie; Lai, Timothy Y Y
Purpose To report a case of central serous chorioretinopathy after solar eclipse viewing. Case Report A middle-age man developed a sudden-onset unilateral scotoma after viewing a partial solar eclipse in Hong Kong. Fundus examination, fluorescein angiography, and optical coherence tomography showed features compatible with central serous chorioretinopathy. The patient was managed conservatively and reevaluated periodically. Serial optical coherence tomographic evaluations demonstrated an initial increase in the amount of subretinal fluid which spontaneously resolved 10 weeks after the onset of symptoms. Conclusion This case demonstrates the possibility of development of central serous chorioretinopathy following solar eclipse viewing. PMID:22737356
Green, Ann E.; Nielsen, Julie S.; Nelson, Brad H.; Drescher, Charles W.; Brown, Patrick O.
Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5′ exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3′ exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer. PMID:21949640
American Psychiatric Association. Borderline personality disorder. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013:663-666. Blais MA, Smallwood P, Groves ...
Green, Maurice R.
Describes characteristics of borderline adolescents and reviews diagnostic issues. Uses two case studies to illustrate general treatment strategies that could be useful to clinicians in mental health programs and family courts. (JAC)
Green, Maurice R.
Describes characteristics of borderline adolescents and reviews diagnostic issues. Uses two case studies to illustrate general treatment strategies that could be useful to clinicians in mental health programs and family courts. (JAC)
Ovarian serous cystadenocarcinoma is a common malignant tumor of female genital organs. Treatment is generally less effective as patients are usually diagnosed in the late stage. Therefore, a well-designed prognostic marker provides valuable data for optimizing therapy. In this study, we analyzed 303 samples of ovarian serous cystadenocarcinoma and the corresponding RNA-seq data. We observed the correlation between gene expression and patients' survival and eventually established a risk assessment model of five factors using Cox proportional hazards regression analysis. We found that the survival time in high-risk patients was significantly shorter than in low-risk patients in both training and testing sets after Kaplan-Meier analysis. The AUROC value was 0.67 when predicting the survival time in testing set, which indicates a relatively high specificity and sensitivity. The results suggest diagnostic and therapeutic applications of our five-gene model for ovarian serous cystadenocarcinoma. PMID:27478834
Togami, Shinichi; Sasajima, Yuko; Kasamatsu, Takahiro; Oda-Otomo, Rie; Okada, Satoshi; Ishikawa, Mitsuya; Ikeda, Shun-ichi; Kato, Tomoyasu; Tsuda, Hitoshi
Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed to characterize the immune profile and human papillomavirus (HPV) status of SACC, in comparison with other serous adenocarcinomas arising in the female genital tract. The pathological specimens obtained from 81 patients with serous carcinoma of the uterine cervix (n = 12), 29 endometrium, 20 ovary and 20 patients with mucinous carcinoma of the uterine cervix were reviewed. We assessed the expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA), and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in very few SACC samples (0 and 0%, respectively), but p16, CA125, CEA and p53 were present in 100, 92, 58 and 50%, respectively. The difference in WT-1 expression between SACC and UPSC, MEA is not significant, but SACC differ significantly from OSA (p < 0.01). HPV DNA (type 16 or 18) was detected in 4 of the 12 SACC. The immunophenotype of SACC was similar to UPSC, whereas the frequency of expression of WT-1 was significantly lower in SACC than OSA. It appeared that p53 expression was associated with worse clinical outcome in patients with SACC, and that HPV infection was related to its occurrence.
Hunter, Sally M; Anglesio, Michael S; Ryland, Georgina L; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M; Doyle, Maria A; Li, Jason; Gilks, C Blake; Moss, Phillip; Allan, Prue E; Stephens, Andrew N; Huntsman, David G; deFazio, Anna; Bowtell, David D; Gorringe, Kylie L; Campbell, Ian G
Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors.
Hunter, Sally M.; Anglesio, Michael S.; Ryland, Georgina L.; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M.; Doyle, Maria A.; Li, Jason; Gilks, C. Blake; Moss, Phillip; Allan, Prue E.; Stephens, Andrew N.; Huntsman, David G.; deFazio, Anna; Bowtell, David D.
Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors. PMID:26506417
Hisada, H; Awaya, S
Central serous chorioretinopathy (CRS) is one of the typical diseases that accompany micropsia. However very little is known about micropsia of CRS, because of the difficulty to measure "aniseikonia" in terms of micropsia. Aniseikonia in 65 cases of CRS was measured quantitatively by Awaya's New Aniseikonia Tests (NAT). The tests were performed at two different distances of 40 cm (visual angle: 6 degrees) and 20 cm (12 degrees) and under 4 meridians of the halfmoon on NAT, horizontal, 45 degrees, vertical and 135 degrees, respectively. The mean value of aniseikonia under each testing condition was as follows: 6 degrees horizontal -3.13%, 45 degrees -2.56%, vertical -2.13%, 135 degrees -2.57%, 12 degrees; horizontal -1.38%, 45 degrees -1.69%, vertical -1.84%, 135 degrees -1.50%. At 6 degrees aniseikonia is larger in the horizontal meridian than in the vertical with statistical significance (t-test, p less than 0.05), while at 12 degrees aniseikonia is smaller than at 6 degrees and shows no particular tendency in terms of meridian. The phenomenon observed at 6 degrees may be what is called "oriented metamorphopsia".
A general survey of the borderline literature is presented. The diagnostic label "borderline" has predominantly been used in North America; nevertheless, many roots of this conception originate in the classical European psychiatry and psychoanalysis. The various diagnostic (mainly descriptive) criteria and characteristics of the borderline are discussed, as well as the most important psychoanalytic hypotheses and conceptions (such as splitting, projective identification, identity diffusion). The therapeutic principles are mentioned as well. The analysis of the surveyed literature reveals on the one hand, that a well defined borderline exists neither as a generally acknowledged clinical entity nor as a circumscribed psychopathological syndrome. On the other hand, there are three various borderline concepts clearly discernible: 1) borderline conceptualized as a form of schizophrenia, 2) borderline conceptualized as synonymous with the general category of psychopathy (personality disorder) and 3) borderline conceptualized as a special form of psychopathy.
Buza, Natalia; Hui, Pei
Significant heterogeneity of HER2 protein expression has been recently observed in HER2 positive endometrial serous carcinomas. Tumor cells with HER2 overexpression and/or gene amplification in a heterogeneous tumor may represent a biologically more aggressive subclone that is clinically relevant to prognosis and potential targeted therapy. To correlate with HER2 protein heterogeneity, we investigated the heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma. A total of 17 endometrial serous carcinomas with heterogeneous HER2 protein expression were selected for the study, including nine cases with a 3+ and eight cases with a 2+ immunohistochemical score. Initial reflex HER2 FISH was available for seven of the eight 2+ cases, five of which showed HER2/NEU gene amplification. All 17 cases underwent repeat FISH targeting larger tumor tissue areas. Ten cases (72%) displayed striking heterogeneity of HER2/NEU gene copy number in the form of cluster amplification. Diffuse HER2 amplification was observed in four cases, no amplification was seen in three tumors. In cases with cluster amplification, HER2 protein overexpression by immunohistochemistry closely correlated at the cellular level with HER2/NEU gene amplification. In conclusion, the significant percentage of cases with heterogeneous HER2/NEU gene amplification indicates that the existing HER2 testing guidelines designed for breast cancer may not be applicable to endometrial serous carcinoma. Clinical testing on multiple different tumor samples or large tumor tissue sections is recommended for both immunohistochemistry and FISH assessment of HER2 status. Direct comparison with the HER2 immunostaining pattern may be helpful in detecting HER2 amplified areas in a heterogeneous tumor.
Bousquet, Elodie; Beydoun, Talal; Rothschild, Pierre-Raphaël; Bergin, Ciara; Zhao, Min; Batista, Rui; Brandely, Marie-Laure; Couraud, Benedicte; Farman, Nicolette; Gaudric, Alain; Chast, François
Purpose: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. Methods: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. Results: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0–Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. Conclusion: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo. PMID:26017871
Yemelyanova, Anna; Ji, Hongxiu; Shih, Ie-Ming; Wang, Tian-Li; Wu, Lee-Shu-Fune; Ronnett, Brigitte M
Uterine serous carcinomas typically have a characteristic morphology (papillary architecture, high-grade nuclei) and immunoprofile (diffuse/strong p53 expression, loss of hormone receptor expression) that distinguish them from most endometrial endometrioid carcinomas. However, glandular variants of serous carcinoma can simulate Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade 2 endometrioid carcinomas, and some serous carcinomas lack p53 expression and retain hormone receptor expression, making classification difficult. P16 expression patterns distinguish endometrioid carcinomas (patchy) from human papillomavirus (HPV)-related endocervical adenocarcinomas (diffuse/strong) but utility for distinction of serous carcinomas from endometrioid carcinomas and endocervical adenocarcinomas has not been evaluated in a large series. Immunohistochemical analysis of p16 expression was performed on 201 uterine and endocervical adenocarcinomas in hysterectomy specimens, including 49 serous carcinomas, 101 endometrial endometrioid carcinomas (44 FIGO grade 1, 40 FIGO grade 2, and 17 FIGO grade 3), and 51 HPV-related endocervical adenocarcinomas. All serous carcinomas demonstrated diffuse/moderate-strong p16 expression, with percentage of positive tumor cells ranging from 90% to 100% (mean/median: 95%/100%). In contrast, endometrial endometrioid carcinomas exhibited less diffuse and less intense expression, with percent of positive tumor cells ranging from 10% to 90% (mean/median: 38%/30%; staining intensity: variable). Similar to serous carcinomas, all endocervical adenocarcinomas exhibited diffuse/moderate-strong p16 expression, with percentage of positive tumor cells ranging from 90% to 100% (mean/median: 94%/90%). P16 can serve as an additional diagnostic marker, used as part of an immunohistochemical panel, including p53 and hormone receptors, for distinction of uterine serous carcinomas from endometrioid carcinomas. Distinction of serous carcinomas
Wei, Linxuan; Liu, Xiaolin; Zhang, Wenjing; Wei, Yuyan; Li, Yingwei; Zhang, Qing; Dong, Ruifen; Kwon, Jungeun Sarah; Liu, Zhaojian; Zheng, Wenxin; Kong, Beihua
The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor highly expressed in fetal tissue and malignant tumors but rarely detected within normal adult tissues. The clinical implications and biological functions of HMGA2 in endometrial carcinoma are largely unknown. Here we report that HMGA2 expression was barely detected in benign endometrium samples (2 of 28 samples). However, HMGA2 expression increased significantly from precancerous lesion endometrial glandular dysplasia (7 of 17, 41.2%), to serous endometrial intraepithelial carcinoma (5 of 8, 62.5%) and to full blown endometrial serous carcinoma (39 of 59, 66.1%). Functional characterization of HMGA2 revealed that the gene has both tumor growth promotion and metastasis. In addition, HMGA2 induced epithelial-mesenchymal transition (EMT) through modulation vimentin and β-catenin. Furthermore, HMGA2 overexpression started from endometrial serous precancers, non-invasive cancers, as well as in full blown carcinomas in a p53 knockout mouse model we recently established in our laboratory. Our findings suggest that HMGA2 may serve as a useful diagnostic marker in the assessment of endometrial serous cancer and its precursor lesions.
Mizuguchi, Keishi; Minato, Hiroshi; Yoshida, Isao; Iwadare, Junpei; Kayahashi, Kayo; Mitani, Yuki; Watanabe, Kazuyoshi
Gastric metastasis from ovarian cancer is exceptionally rare and generally occurs in advanced stages. A 71-year-old woman presented with a solitary gastric submucosal mass 8 years after the diagnosis of a stage IA ovarian serous adenocarcinoma. Endoscopy showed a tumor covered with normal gastric mucosa. Initially, a gastrointestinal stromal tumor was suspected, but biopsy revealed a histology of invasive micropapillary carcinoma, similar to the histological findings of the previously resected ovarian tumor. Clinicians should consider that in patients with a submucosal tumor and a history of ovarian cancer, gastric lesions may be secondary metastases from ovarian cancer. PMID:28420839
Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, KN Chandan; Rastogi, Archana
Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures. PMID:24782930
... to environmental factors — such as a history of child abuse or neglect — borderline personality disorder may be linked ... Do you use alcohol or recreational drugs or abuse prescription drugs? How ... neglected as a child? Have any of your close relatives or caregivers ...
Sipos, V; Schweiger, U
Characteristics of a borderline personality disorder include emotional instability and a self-threatening lack of impulsive control. As a result, interpersonal relationships are rendered difficult. The central elements of treatment are psychoeducation, self-management, improved stress tolerance and awareness, emotion managment and training in social competence.
has used virus extracts to increase whole-cell vaccine immuno- genicity, based on the observation that viruses can be highly inflammatory. This led to...molecular targets for future development of cancer targeted therapy . 3 lesions and normal tissues that could serve as an important research tool for...potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations. Cancer Res 65:1994-2000, 2005. K concepts and conundrums
TAJIMA, HIDEHIRO; OHTA, TETSUO; KITAGAWA, HIROHISA; SHINBASHI, HIROYUKI; HIROSE, ATSUSHI; SAKAI, SEISHO; MAKINO, ISAMU; HAYASHI, HIRONORI; NAKAGAWARA, HISATOSHI; ONISHI, ICHIRO; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; FUSHIDA, SACHIO; TANI, TAKASHI; FUJIMURA, TAKASHI; KAYAHARA, MASATO; KODA, WATARU; MATSUI, OSAMU
Serous microcystic adenomas are rare and account for 1–2% of all exocrine pancreatic tumors and 25% of all pancreatic cystic neoplasms. Recently, with advances in imaging techniques, these adenomas have been identified at an increasing frequency. A 63-year-old woman visited her doctor in 1999 due to a gastric deformity detected by upper gastrointestinal endoscopy. An abdominal computed tomography scan revealed a cystic lesion measuring 6.0 cm in diameter, resulting in a diagnosis of serous microcystic adenoma of the pancreatic head. During follow-up, the tumor increased steadily in size, measuring 6.0 cm in diameter in 1999 and 13.0 cm in 2008, while remaining asymptomatic throughout this period of time. The risk of malignant transformation appears to be low even over the long-term. However, some cases of malignant transformation to serous cystadenocarcinoma have recently been reported. In this case, assessment of the relationship between the tumor and adjacent vascular structures, such as massive drainage vein development on the surface or tumor flow into the portal and superior mesenteric veins and the celiac and superior mesenteric arteries, was critical for determining tumor resectability. The risk of massive intra-operative hemorrhage was felt to be considerable, given the extent of the veins on the surface of the tumor, as well as the size and location of the primary pancreatic mass. Therefore, preoperative embolization of the tumor-feeding arteries arising from the celiac axis (gastroduodenal, splenic and dorsal pancreatic arteries) was performed. Tumor resection with pancreaticoduodenectomy was performed without a blood transfusion, with an estimated blood loss of 570 ml. The final pathology confirmed the diagnosis of serous microcystic adenoma. The patient is currently alive and disease-free. Preoperative partial embolization of the tumor feeding arteries and intra-operative resection of the right gastric and inferior pancreatoduodenal arteries, allowed
Peng, Jin; Yoshioka, Yumiko; Mandai, Masaki; Matsumura, Noriomi; Baba, Tsukasa; Yamaguchi, Ken; Hamanishi, Junzo; Kharma, Budiman; Murakami, Ryusuke; Abiko, Kaoru; Murphy, Susan K; Konishi, Ikuo
Members of the transforming growth factor-β (TGF-β) superfamily transduce signals via SMAD proteins. SMAD2 and SMAD3 mediate TGF-β signaling, whereas SMAD1, SMAD5, and SMAD8/9 transduce bone morphogenetic protein (BMP) signals. We would like to identify the function of BMP/SMAD5 signaling in serous ovarian cancer. The protein levels of total SMAD5 and phosphorylated SMAD5 (pSMAD5) were examined by immunohistochemical analysis using clinical serous ovarian cancer samples. Following treatment with either recombinant BMP2 (rBMP2) or Dorsomorphin (DM), western blotting was performed to observe pSMAD5 protein in the cytoplasm and the nucleus, separately. Cell proliferation was detected in SMAD5 knockdown serous ovarian cancer cell lines cultured with DM or rBMP2. The impact of DM or rBMP2 on tumor growth was observed in a mouse model of serous ovarian cancer. An inverse correlation was observed between pSMAD5 levels in the nucleus and the prognosis of patients with serous ovarian cancer. The treatment of SK-OV-3 with rBMP2 stimulated pSMAD5 translocation from the cytoplasm to the nucleus, and the addition of DM inhibited this effect. The proliferation of ovarian cancer cell lines was enhanced by BMP2 and suppressed by DM via SMAD5 in vitro. In vitro and in vivo experiments clearly demonstrated BMP2-stimulated proliferation of serous ovarian cancer and inhibition of this effect by DM. Our data suggests that BMP/SMAD5 signaling plays an important role and, therefore, becomes a potential therapeutic target in serous ovarian cancer. © 2015 Wiley Periodicals, Inc.
Grabowski, Jacek P; Harter, Philipp; Heitz, Florian; Pujade-Lauraine, Eric; Reuss, Alexander; Kristensen, Gunnar; Ray-Coquard, Isabelle; Heitz, Julia; Traut, Alexander; Pfisterer, Jacobus; du Bois, Andreas
Since almost two decades standard 1st-line chemotherapy for advanced ovarian cancer (AOC) has been a platinum/taxane combination. More recently, this general strategy has been challenged because different types of AOC may not benefit homogenously. Low-grade serous ovarian cancer (LGSOC) is one of the candidates in whom efficacy of standard chemotherapy should be revised. This study is an exploratory case control study of the AGO-metadatabase of 4 randomized phase III trials with first-line platinum combination chemotherapy without any targeted therapy. Patients with advanced FIGO IIIBIV low-grade serous ovarian cancer were included and compared with control cases having high-grade serous AOC. Out of 5114 patients in this AGO database 145 (2.8%) had LGSOC and of those thirty-nine (24.1%) had suboptimal debulking with post-operative residual tumor >1cm, thus being eligible for response evaluation. An objective response was observed in only 10 patients and this 23.1% response rate (RR) was significantly lower compared to 90.1% RR in the control cohort of high-grade serous ovarian cancer (HGSOC) (p<0.001). Both, LGSOC and HGSOC patients who underwent complete cytoreduction had significantly better progression free survival (PFS) and overall survival (OS) in comparison to those with residuals after primary surgery, accordingly (p<0.001). Our observation indicates that low-grade serous cancer is not as responsive to platinum-taxane-based chemotherapy as high-grade serous AOC. In contrast, surgical debulking showed a similar impact on outcome in both types of AOC thus indicating different roles for both standard treatment modalities. Systemic treatment of low grade serous AOC urgently warrants further investigations. Copyright © 2016 Elsevier Inc. All rights reserved.
Chivukula, Mamatha; Dabbs, David J; O'Connor, Siobhan; Bhargava, Rohit
Ovarian serous papillary carcinoma, although rarely metastasizing to the breast, is often challenging based on morphology alone, particularly from the micropapillary variant of breast carcinoma. Gross cystic disease fluid protein-15, although a specific marker, can be negative in up to 50% of breast carcinomas. Wilm's tumor gene 1 (WT-1) has been identified as a useful marker to differentiate metastatic ovarian serous papillary carcinoma from primary breast carcinoma; however, it has recently been shown in the micropapillary variant of the primary breast carcinoma making it a less specific marker. PAX 2, a nuclear transcription factor, was recently observed in ovarian serous papillary carcinomas. In this study of 89 breast carcinoma cases, 26 micropapillary carcinoma, and 63 nonmicropapillary carcinoma types were retrieved from our pathology archives, represented on a single tissue microarray (TMA) with a 3-fold redundancy (TMA-1, TMA-2). In addition, whole tissue sections of a variety of benign and neoplastic müllerian tissues were surveyed with the PAX 2 immunostain. All cases were stained with rabbit polyclonal PAX 2 antibody and, in addition, the 5 metastatic ovarian serous carcinoma cases were stained with WT-1 as well for comparison. Only nuclear staining was considered positive. All primary breast carcinomas represented on TMA-1 and TMA-2 were entirely negative for PAX 2 100% (89/89), whereas 100% (5/5) of all metastatic ovarian serous carcinomas showed moderate-to-strong staining. PAX 2 expression was comparable with WT-1 as well in the metastatic ovarian serous carcinoma group. We therefore conclude that PAX 2 is a promising new, sensitive, and specific müllerian immunomarker for ovarian serous carcinomas (primary and metastatic).
Wang, Hangjun; Chen, Patrick C
Primary peritoneal carcinoma (PPC) is a relatively uncommon malignancy, and its presentation is similar to that of advanced ovarian serous carcinoma. There have been afew case reports in which the malignant cells from PPC were discovered from routine Papanicolaou (Pap) smears. In 2006 a 49-year-old, asymptomatic female participated in the Hospital Health Fair. High grade adenocarcinoma was found by Pap smear. After negative cervical and endometrial curetting and loop electrosurgical excision procedure cone, laparoscopy revealed widespread peritoneal carcinomatosis. The subsequent surgical specimens showed primary peritoneal serous carcinoma. Although the Pap smear was originally designed to detect premalignant cervical lesions and cancer, it became apparent that malignant cells from extrauterine primaries might appear in the smears. This case illustrated the value of the Pap smear in discovering unsuspected extrauterine malignancies, including PPC. Review of 9 cases showed tumor cells in the fallopian tube lumen in 4 out of 9 cases, indicating the likely route of efflux of tumor cells to appear in the Pap smear. The new concept of serous tubal intraepithelial carcinoma as the origin of PPC suggests another source of tumor cells in Pap smears.
Gil, Tsvi E
Borderline personality is a well known concept in psychiatric literature, however, not fully understood as to its very nature. This article presents a short review of hypothesized etiologies of the borderline personality, starting with so called traditional theories, namely, borderline personality as a consolidated personality organization, in which the patient pathologically deals with his or her inner aggression, or with an enduring developmental failure. More modern hypotheses focus on possible childhood sexual abuse as the origin of the borderline, viewing the adult personality as a chronic, unresolved, post-traumatic disorder. Additionally, a neuro-epigenetic view hypothesized that a unique congenital neurological structure interacts with consequential events in early childhood to create the borderline personality.
histological subtype of ovarian cancer and is the most lethal gynecologic malignancy. The relationship between stage at presentation and survival in serous ...among and within stages of epithelial ovarian cancer , focusing on serous , mucinous and endometrioid subtypes (1-18 Months). a. Collections and...not serous or mucinous epithelial ovarian tumors. Cancer Res 58: 2095-2097, 1998. 7. Aikhionbare FO et al:.: Is cumulative frequency of mitochondrial
Malmberg, Karin; Klynning, Charlotta; Flöter-Rådestad, Angelique; Carlson, Joseph W
Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p < 0.001). No differences in tubal injury or inflammation were seen when comparing the sporadic serous cancer group and the control group or within the hereditary group. STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.
Hasby, Eiman Adel
This study aims to investigate the immunohistochemical expression of mammary serine protease inhibitor (maspin) and CD138 in primary ovarian high-grade serous carcinomas (HGSC) as compared to low-grade serous carcinomas (LGSC) and clear cell carcinomas and investigate if the studied markers have a correlation to International Federation of Gynaecology and Obstetrics (FIGO) stage, Ki67 proliferation index, and to each other. Maspin cellular location varied significantly between studied groups with only nuclear expression seen in 46.7 % of LGSC group, mixed nuclear and cytoplasmic in 13.3, 28.6, and 20 % of LGSC, HGSC, and clear cell carcinoma, respectively, and was only cytoplasmic in 26.7, 71.4, and 80 % of LGSC, HGSC, and clear cell carcinoma, respectively. Mean maspin and CD138 counts were significantly higher in HGSC and clear cell carcinoma compared to LGSC. Both maspin and CD138 scores varied significantly between studied groups and were positively correlated with adverse prognostic factors in studied carcinomas including FIGO stage and Ki67 proliferation index. Besides, both maspin and CD138 had significant correlation to each other. These findings suggest that epithelial cytoplasmic expression of maspin and CD138 may have a significant role in tumorigenesis in ovarian high-grade serous carcinomas and clear cell carcinomas; these markers may regulate tumor cell proliferation, and their significant correlation to each other may suggest that CD138 probably induces maspin expression to protect tumor growth factors from being lysed by proteolytic enzymes.
El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D
Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs.
Munteanu, M; Giuri, Stela; Rosca, C; Boruga, O; Chercota, V; Stanca, H T
Choroidal hemangiomas are benign vascular hamartomas that typically present from second to fourth decade of life, when they can cause visual disturbance due to exudative retinal detachment. They represent uncommon benign choroidal vascular tumors, usually occuring sporadically in the absence of systemic disease. We report the case of a young female patient, presenting a juxtapapillary circumscribed choroidal haemangioma complicated with serous macular detachment. The patient underwent photodynamic therapy with verteporfin (PDT). Systematic follow-up using ophthalmoscopy, ultrasonography, Fluorescein angiography and Indocyanine green angiography was performed. The patient presented regression with flattening of tumour, resolution of the subretinal fluid, and significant improvement of vision. Mostly asymptomatic, the choroidal hemangiomas can be associated with serous retinal detachment, leading to reduced vision and metamorphopsia; in those cases, the long term visual prognosis is poor, even in adequately treated patients. PDT is effective in eliminating the subretinal fluid and improving vision in patients with circumscribed choroidal hemangioma.
Quddus, M Ruhul; Sung, C James; Zhang, Cunxian; Lawrence, W Dwayne
Most endometrial carcinomas contain only 1 Müllerian cell type although the presence of 2 or more cell types within 1 tumor, for example a predominantly low-grade endometrioid carcinoma with a minor component (arbitrarily defined as 30% or less) of high-grade serous and/or clear cell carcinoma, is not uncommon. The current study attempts to evaluate whether the presence of minor serous or clear cell components exerts an adverse effect on the prognosis in stage-I endometrial carcinomas of ''mixed-type.'' The study cases include 22 cases of stage-I endometrioid carcinoma with a minor component of serous carcinoma and 14 cases of endometrioid carcinoma with a minor component of clear cell carcinoma. Minor components were arbitrarily defined as representing anywhere between 5% and 30% of the total tumor. The study cases were compared with 56 cases of histologically pure age-matched and stage-matched endometrioid carcinomas, 6 pure serous carcinomas, and 13 pure clear cell carcinomas. All study and control cases were fully staged. Treatment history and outcome status were obtained and follow-up ranged from 56 to 140 months. Our study suggests that the presence of minor components of serous and clear cell carcinoma, defined as between 5% and 30%, within a mixed-type endometrial carcinoma appears to adversely influence the long-term survival of stage-I tumors, although a larger study is needed to corroborate our findings.
Targarona, Javier; Garatea, Rafael; Romero, Cesar; Rosamedina, José Luís; Lora, Alfonso; Beltrán, Jorge; Rotta, César; Tapia, Pedro; Montoya, Eduardo
The cystic tumor of the pancreas is a relatively uncommon entity. There are different types of pancreatic cystic tumors and they all exhibit different degrees of malignancy. These tumors represent 1% of all primary pancreatic tumors and only 15% of the cystic lesions. The serous cystadenomas (SCA) are mostly benign lesions with an average size of 4 cm; nevertheless, in some rare cases these are giant lesions, generally larger than 15 cm. Sometimes these tumors produce a symptomatology caused by the compression of neighboring structures, therefore they are generally operable. During the period from June 2004 to June 2005, the 3A II unit of the Edgardo Rebagliati Martins Hospital operated on two cases of giant serous cystadenomas of the pancreas, one located in the tail of the pancreas and the other in the head of the pancreas, with an average size of 16 cm. The giant SCAs of the pancreas are rarely seen lesions that, according to different authors, are usually larger than 10 to 15 cm. in diameter. These lesions do not represent a diagnosis problem and are generally operable since they produce a symptomatology by compression. The surgical resection can be complicated due to their large size and to the considerable neovascularization.
Chanen, Andrew M; Thompson, Katherine N
Summary Accurate diagnosis is fundamental to effective management of borderline personality disorder, but many patients remain undetected. The first-line management for borderline personality disorder is psychosocial treatment, not drugs. There are major prescribing hazards including polypharmacy, overdose and misuse. Drug treatment might be warranted for patients who have a co-occurring mental disorder such as major depression. If a drug is prescribed for borderline personality disorder, it should only be as an adjunct to psychosocial treatment. There should be clear and collaborative goals that are regularly reviewed with the patient. Use single drugs prescribed in limited quantities for a limited time. Stop drugs that are ineffective. PMID:27340322
Dietrich, Kevin C
Central serous chorioretinopathy (CSC) is usually a self-limiting condition; however, there is potential for recurrence and permanent visual defects. Aviation demands perfect vision to minimize risk to pilots and aircraft. Consequently, this ailment disqualifies pilots and pilots to be. A fully trained fighter pilot with 1260 h in fighter airframes has been contending with central serous chorioretinopathy in the right eye over the course of 3 yr. The condition was diagnosed after the member presented with visual disturbances. His course was followed with multiple treatment modalities: watchful waiting, micropulse laser, and rifampin. His disease responded well with rifampin, but was ultimately stopped secondary to elevated liver enzymes. Micropulse laser failed to resolve subretinal fluid. Ultimately the pilot is left with a chronic area of CSC without visual defects and faces career termination. Uncompromised vision is inherently crucial in aerospace careers, especially that of a fighter pilot. With persistent CSC resistant to treatment, there is a risk for progression to permanent visual disturbances and/or defects. Safety concerns of authority figures overseeing pilots and aircraft are warranted. However, the concern could be mitigated in air frames that require two pilots. Another factor partially responsible for ending his career is the fear of G force affecting his prognosis. The author is not aware of any other studies illuminating the effects or consideration of excess G force on subretinal fluid in CSC. This is an area that requires further study. Dietrich KC. Fighter pilot with recurrent central serous chorioretinopathy. Aerosp Med Hum Perform. 2016; 87(10):901-905.
Chen, Wenqian; Husain, Arjumand; Nelson, Gregg S; Rambau, Peter F; Liu, Shuhong; Lee, Cheng-Han; Lee, Sandra; Duggan, Máire A; Köbel, Martin
Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%-98%] and specificity of 87.8% (95% CI, 75%-95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%-99%) and specificity of 72.2% (95% CI, 46%-90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%-79%) and specificity of 98.0% (95% CI, 94%-99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.
Malpica, Anais; Deavers, Michael T; Tornos, Carmen; Kurman, Robert J; Soslow, Robert; Seidman, Jeffrey D; Munsell, Mark F; Gaertner, Erich; Frishberg, David; Silva, Elvio G
Although grading has been demonstrated to be an important prognostic factor in ovarian serous carcinoma, there is no system universally used to perform this task. A few years ago, we proposed a two-tier system for grading ovarian serous carcinoma that is based primarily on the assessment of nuclear atypia (uniformity vs. pleomorphism) in the worst area of the tumor. Tumor grade in this two-tier system is correlated with survival. After being used by numerous pathologists and trainees at The University of Texas M.D. Anderson Cancer Center (MDACC) for 15 years, we have observed that this system is user-friendly and reproducible. We undertook this study to evaluate the interobserver and intraobserver variability among a group of 7 gynecologic pathologists and 2 general surgical pathologists using this grading system. A total of 80 cases of ovarian serous carcinoma, 40 low-grade and 40 high-grade, were circulated twice among these pathologists. Slides with examples of low-grade and high-grade serous carcinoma were sent with the unknowns. A website was used to provide diagnostic criteria, images of examples of ovarian low-grade and high-grade carcinoma, and a log form to facilitate data entry. Statistical analysis demonstrated an overall kappa statistic among the different observers of 0.909. The intergrader kappa's ranged from 0.717 to 1.000 in the first round of the review and from 0.701 to 1.000 in the second round. Eight of the participants had an intragrader kappa ranging from 0.775 to 1.000 (excellent agreement), whereas a single participant had an intragrader kappa of 0.725 (good agreement). This study demonstrates that the two-tier grading system (the MDACC grading system) for ovarian serous carcinoma on the basis of the assessment of nuclear atypia is easy to learn and is highly reproducible. These findings would support its universal use, which would be beneficial for the standardization of clinical trials and protocols, thus facilitating the understanding of
Huntsman, David; Resau, James H.; Klineberg, Eric; Auersperg, Nelly
The transmembrane tyrosine kinase receptor c-met with its ligand, hepatocyte growth factor/scatter factor (HGF/SF), acts as a mitogen, motogen, and morphogen in many normal epithelia. HGF/SF-met signaling has also been implicated in neoplastic progression and metastasis. In this study, immunofluorescence staining and quantitative laser scanning confocal microscopy were used to measure c-met expression in ovarian surface epithelial tumors from 17 oophorectomy specimens. These specimens were from patients aged 25 to 81 (mean age, 52) and included 10 malignant tumors, 4 borderline tumors, and five benign tumors including a Brenner tumor. For comparison, c-met expression was measured in normal tissues from the same patients, including 4 ovarian surface epithelia, 4 fallopian tube epithelia, 2 endometria, and 3 endocervical epithelia, as well as 3 cases of endometriosis. Relative pixel intensity values of c-met expression ranged from 0.4 in a normal ovarian surface epithelium to 22.3 in a borderline serous tumor. Malignant tumors (mean, 9.6) and borderline tumors (mean, 12.9) had higher average c-met expression levels than normal tissues (mean, 3.6) and endometriosis (mean, 1.8). The expression levels of benign tumors were intermediate (mean, 7.9). Among the normal tissues, c-met expression in fallopian tubes (mean, 8.2; range, 3.4–12.9) was higher than that of the other normal epithelia (mean, 1.6; range, 0.4–4.3). In eight cases where both normal and malignant tissues were sampled, c-met expression was significantly greater in malignant than in normal epithelia (P = 0.01). These findings indicate that c-met plays a role in the biology of the normal tissues examined. They confirm that its expression increases in the malignant progression of ovarian surface epithelial tumors, and suggest that increases comparable to those in frankly malignant carcinomas have already been reached in borderline lesions, ie, early in the neoplastic process. PMID:10433927
Chui, M Herman; Wang, Yihong; Wu, Ren-Chin; Seidman, Jeffrey; Kurman, Robert J; Wang, Tian-Li; Shih, Ie-Ming
Tumor-initiating cells are thought to share features with normal somatic stem cells. In mice, stem cells at the ovarian hilum have been shown to express the stem cell marker, aldehyde dehydrogenase isoform 1A1 (ALDH1A1), and are prone to malignant transformation. The potential relevance of this finding to humans has not been established. In this study, we used immunohistochemistry to assess the distribution of ALDH1A1 staining in the epithelium of human fallopian tubes, with particular reference to the transition of tubal epithelium to mesothelium (ie, tubal-mesothelial junction), ovarian surface epithelium, as well as putative precursors of ovarian high-grade serous carcinoma, namely, serous tubal intraepithelial carcinoma and 'p53 signatures,' and overt serous carcinoma. Expression of ALDH1A1 was detected in both secretory and ciliated tubal epithelial cells, tubal-mesothelial junctions and ovarian surface epithelium, but was absent in serous tubal intraepithelial carcinoma and p53 signatures. Positive staining in high-grade serous carcinoma, when present, was typically limited to rare tumor cells. In silico analyses of the mRNA expression data set from The Cancer Genome Atlas revealed downregulation of ALDH1A1 transcripts in high-grade serous carcinoma relative to normal tubal epithelium, and no association between ALDH1A1 expression levels and overall survival. Our results do not support ALDH1A1 as a specific marker of stem cells in human fallopian tube and demonstrate that its loss of expression is an early event in the development of high-grade serous carcinoma.
Ricardo, Sara; Marcos-Silva, Lara; Pereira, Daniela; Pinto, Rita; Almeida, Raquel; Söderberg, Ola; Mandel, Ulla; Clausen, Henrik; Felix, Ana; Lunet, Nuno; David, Leonor
The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions, in both series. An even better yield was obtained based on positivity for any of the four glyco-mucin profiles, further increasing sensitivity to 72% and 83% in the two series, respectively, with 100% specificity. The strategy is designated glyco-mucin profiling and provides strong support for development of PLA-based serum assays for early diagnosis.
Forooghian, Farzin; Meleth, Annal D.; Cukras, Catherine; Chew, Emily Y.; Wong, Wai T.; Meyerle, Catherine B.
Purpose To evaluate the safety and efficacy of finasteride, an inhibitor of dihyroxytestosterone (DHT) synthesis, in the treatment of chronic central serous chorioretinopathy (CSC). Methods Five patients with chronic CSC were prospectively enrolled in this pilot study. Patients were administered finasteride (5mg) daily for 3 months, following which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity (BCVA), center-subfield macular thickness and subretinal fluid volume as assessed by optical coherence tomography (OCT). Serum DHT, serum testosterone, and urinary cortisol were also measured. Results There was no change in mean BCVA. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months, and rose to levels that were below baseline by 6 months. The changes in both OCT parameters paralleled changes in serum DHT level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased following discontinuation of finasteride. In the remaining patient, both OCT parameters normalized with finasteride and remained stable when the study medication was discontinued. Conclusion Finasteride may represent a novel medical treatment for chronic CSC. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of CSC. Summary Pilot study to evaluate finasteride for treatment of chronic central serous chorioretinopathy suggests efficacy and tolerability. PMID:21273946
Milea, Anca; George, Sophia H L; Matevski, Donco; Jiang, Haiyan; Madunic, Mary; Berman, Hal K; Gauthier, Mona L; Gallie, Brenda; Shaw, Patricia A
Alterations in the retinoblastoma pathway are frequent in ovarian/tubal high-grade serous cancers, but the mechanism of deregulation and the impact on patient outcome are poorly understood. A cohort of 334 high-grade serous carcinomas was studied by immunohistochemical analysis of RB1, p16, cyclin D1, cyclin E1, and Ki67. Additional detailed analyses including RB1 allelic deletion (n=42), mutation (n=75), methylation (n=31), and SNP array analyses (n=75) were performed on cases with clinical parameters, including age, debulking status, treatment, and clinical outcome. p16/RB1 expression results yielded three distinct clinically relevant subgroups upon multivariable analysis controlling for stage, debulking status, and treatment types: p16 homogeneous/RB1+ with the shortest progression-free survival (median 15 months (95% CI: 13-18); P=0.016) compared with the p16 heterogeneous/RB1+ subgroup (median 22 months (95% CI: 16-32)) and the p16 homogeneous/RB1- subgroup (median 20 months (95% CI: 15-24)). Patients in the p16 homo/RB1- subgroup showed a significant increase in overall survival (>60 months; P=0.013), which suggests an increase in sensitivity to cytotoxic agents. Analyses of Rb pathway mechanistic differences among these groups revealed frequent RB1 genomic alterations such as RB1 allelic loss and/or large spanning deletions (83%) in the p16 homo/RB1- subgroups, also indicating that RB1 deletions are frequent in high-grade serous carcinoma. CCNE1 gene gains/amplifications were frequent in the p16 homogeneous/RB1+ subgroup (68%) and cyclin D1 protein overexpression was predominantly characteristic of the p16 heterogeneous/RB1+ subgroup. These subcategories occur early in tumor progression and are seen with similar frequency in the cancer precursor lesion, serous tubal intra-epithelial carcinoma. Overall, this study uniquely identifies multiple non-synonymous mechanisms of retinoblastoma pathway deregulation that correlate with significantly different clinical
Kaldawy, Anis; Segev, Yakir; Lavie, Ofer; Auslender, Ron; Sopik, Victoria; Narod, Steven A
Epithelial ovarian cancers can be divided into the more common, aggressive type II cancers and the less common, slow-growing type I cancers. Under this model, serous ovarian carcinomas can be subdivided into high-grade (type II) and low-grade (type I) tumours. The two-tier system for grading serous ovarian carcinomas is superior to more detailed grading systems in terms of predicting survival. Low-grade serous carcinomas typically present in young women and have a relatively good prognosis, despite being resistant to chemotherapy. Low-grade serous cancers have a high prevalence of KRAS and BRAF mutations, but a low prevalence of TP53 mutations (which are characteristic of high-grade serous cancers). Among women with low-grade serous ovarian cancer, the presence of a KRAS/BRAF mutation is a favorable prognostic factor. Studies of the mitogen-activated protein kinase (MAPK) inhibitor in low-grade serous ovarian cancer suggest that identifying MAPK mutations might eventually be useful in guiding treatment.
The term ‘Borderline Personality Disorder’ (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity. In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral ‘strategy’ which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic ‘deficit’-oriented models, which may have profound implications for therapeutic approaches. PMID:26929090
Kawamura, Ryosuke; Ideta, Hidenao; Hori, Hideyuki; Yuki, Kenya; Uno, Tsuyoshi; Tanabe, Tatsurou; Tsubota, Kazuo; Kawasaki, Tsutomu
Background Central serous chorioretinopathy (CSC) has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT) utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC. Methods We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 μm, and exposure time of 13–60 seconds to minimize retinal damage. Results In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA) ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30). Final BCVA ranged from 20/200 to 20/20 (mean, 20/25; median, 20/20). BCVA improved in all cases. Only two eyes with persistent subretinal fibrin and existing retinal pigment epithelial alternations in macular area showed limited improvement of BCVA despite the absence of
Naumann, R Wendel
Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer that is likely to present with deep myometrial invasion and lymph vascular involvement. By the time most affected women are diagnosed, the UPSC has spread outside the uterus. Because many reports include patients who are not completely staged, the risk of recurrence in stage I patients has likely been overestimated. Recently, several large series of well-staged patients have demonstrated that survival in stage I patients is similar to that of poorly differentiated endometrioid tumors. Because of the high risk of extrauterine spread, all patients with UPSC should have an extended surgical staging procedure, including lymphadenectomy and omentectomy. Chemotherapy with or without local or regional radiation is probably the most effective adjuvant therapy in both early and advanced disease. Because patients with stage I UPSC are still at significant risk of recurrence, adjuvant therapy is often recommended for all patients. It has been difficult to conduct prospective randomized trials for patients with UPSC because of the rare nature of these cancers.
Gil, Tsvi E
The present article critically discusses diagnosing borderline personality, demonstrating ideas raised with a treated case. In contrast to routine diagnoses made by psychiatrists according to common diagnosing systems (such as the American DSM or the WHO's ICD), we wonder whether this diagnosis reflects a medico-social construct, which is associated to the female status in masculine (or even patriarch) society, and probably associated even to the context of a woman diagnosed by a psychiatric system. In the context of critically viewing aetiological hypotheses to borderline personality (presented in our former article as a personality constellated around complex and prolonged trauma) in this article we suggest viewing borderline behaviours and symptoms as manifestations of coping and survival of a woman-victim in abusing surroundings.
Behtash, N; Modares, M; Abolhasani, M; Ghaemmaghami, F; Mousavi, M; Yarandi, F; Hanjani, P
Thirty-eight patients with ovarian tumours of low malignant potential (borderline) were diagnosed and treated in Tehran University Gynecology Oncology Department from 1991 to 2002, and have been reviewed. In this study age, clinical behavior, symptoms, surgical stage, type of tumour, surgery, adjuvant treatment, survival and recurrences were evaluated. A retrospective chart review was performed on these 38 patients who were treated for histopathologically confirmed tumours of low malignant potential between 1991-2002. The mean age was 34.4 years, range (14-83) (SD: 18.33). Post surgical FIGO staging was: Stage I=93.75%, stage III 6.25%. Histologic subtypes were: Serous 76.31% (29 patients), Mucinous 21.05% (8 patients), Mixed types 2.63% (1 patient). Mean pre-operative CA125 value was 114.90 (SD: +/- 90.30). Thirty-three percent of patients had only a simple cyst in ultrasonography. Conservative surgery was performed in 76.32% (29 patients). More radical surgery (TAH + BSO) was performed in 9 patients (23.68%). There were 6 recurrences. Three patients with recurrence and invasive implants received chemotherapy and secondary surgery was performed. Survival rate was 100% at 3 years for all stages and 89% at 5 years. One patient died of recurrent disease at 48 months after initial diagnosis. Our data suggest that LMP tumours are most frequently diagnosed in stage I. Most common histological type was serous, and 5 of the recurrences of (6 patients) were initially diagnosed at stage I, and had been treated with conservative surgery with no adjuvant therapy.
Lopez, Nicole E; Prendergast, Cristina; Lowy, Andrew M
Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection remains the only curative option, more than 80% of patients present with unresectable disease. Unfortunately, even among those who undergo resection, the reported median survival is 15-23 mo, with a 5-year survival of approximately 20%. Disappointingly, over the past several decades, despite improvements in diagnostic imaging, surgical technique and chemotherapeutic options, only modest improvements in survival have been realized. Nevertheless, it remains clear that surgical resection is a prerequisite for achieving long-term survival and cure. There is now emerging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their primary tumor to surrounding vasculature, may benefit from resection, particularly when preceded by neoadjuvant therapy. This stage of disease, termed borderline resectable pancreatic cancer, has become of increasing interest and is now the focus of a multi-institutional clinical trial. Here we outline the history, progress, current treatment recommendations, and future directions for research in borderline resectable pancreatic cancer. PMID:25152577
Evardone, Milagros; Alexander, Gerianne M.; Morey, Leslie C.
Borderline personality is diagnosed in clinical settings three times more often in women than in men, and symptom severity in women appears sensitive to circulating sex steroid levels. In non-human mammals, prenatal hormones contribute to the development of sex-linked behavior and their responsiveness to postnatal hormones. Therefore, this study examined the hypothesis that prenatal hormones may influence the development of borderline personality traits by measuring a marker of perinatal androgen action, the 2D:4D ratio, and salivary hormone levels in 58 men and 52 women. Participants completed the Borderline Features Subscales (BOR) of the Personality Assessment Inventory, gender role questionnaires, and four sex-linked cognitive tasks. Digit ratios were a significant predictor of the affective component of borderline personality, such that in both sexes 2D:4D ratios suggestive of weaker perinatal androgen action contributed to greater borderline personality features overall and greater affective instability. In addition, women reporting greater affective instability showed larger changes in estradiol across the session, consistent with the influence of stress and emotional reactivity on hormonal function. These findings are consistent with an increasing body of research suggesting that hormonal factors associated with the expression of typical gender-linked behavior may also contribute to the expression of gender-linked maladaptive behavior. PMID:19554197
Evardone, Milagros; Alexander, Gerianne M; Morey, Leslie C
Borderline personality is diagnosed in clinical settings three times more often in women than in men, and symptom severity in women appears sensitive to circulating sex steroid levels. In non-human mammals, prenatal hormones contribute to the development of sex-linked behavior and their responsiveness to postnatal hormones. Therefore, this study examined the hypothesis that prenatal hormones may influence the development of borderline personality traits by measuring a marker of perinatal androgen action, the 2D:4D ratio, and salivary hormone levels in 58 men and 52 women. Participants completed the Borderline Features Subscales (BOR) of the Personality Assessment Inventory, gender role questionnaires, and four sex-linked cognitive tasks. Digit ratios were a significant predictor of the affective component of borderline personality, such that in both sexes 2D:4D ratios suggestive of weaker perinatal androgen action contributed to greater borderline personality features overall and greater affective instability. In addition, women reporting greater affective instability showed larger changes in estradiol across the session, consistent with the influence of stress and emotional reactivity on hormonal function. These findings are consistent with an increasing body of research suggesting that hormonal factors associated with the expression of typical gender-linked behavior may also contribute to the expression of gender-linked maladaptive behavior.
Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara
Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. Case Report: A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. Conclusions: UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594
Faluyi, Olusola; Mackean, Melanie; Gourley, Charlie; Bryant, Andrew; Dickinson, Heather O
Background The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. Objectives To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intraperitoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral
Zheng, Wenxin; Yi, Xiaofang; Fadare, Oluwole; Liang, Sharon X; Martel, Maritza; Schwartz, Peter E; Jiang, Zhong
Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but rarely found in adult benign tissues. The aim of this study is to determine the expression of IMP3 in benign endometrium, endometrial cancer, and its precursor lesions, trying to see whether IMP3 has any diagnostic usage. Two hundred ninety-eight endometrial samples were examined for IMP3 expression by immunohistochemistry. These included benign endometrium (n=68), atypical hyperplasia or endometrial intraepithelial neoplasia (n=35), endometrial glandular dysplasia (n=21), endometrial intraepithelial carcinoma (n=18), endometrioid carcinoma (n=70), mucinous carcinoma (n=8), serous carcinoma (n=51), clear cell carcinoma (n=12), and other malignancies (n=15). Maturational patterns in the 68 benign endometrial samples included atrophic (n=12), proliferative (n=18), secretory (n=14), menstrual (n=8), and gestational (n=16). Most of the carcinomas were histologically pure; where mixed, the second component constituted <10% of the total tumor volume. The extent and intensity of IMP3 expression was semiquantitatively determined and scored for all samples. A renal cell carcinoma with known IMP3 expression was used as positive control for each immunohistochemistry run. Among the malignant cases, IMP3 expression was predominantly found in endometrial serous carcinoma and its putative precursor lesions, with 3 (14%) of 21 endometrial glandular dysplasia, 16 (89%) of 18 serous endometrial intraepithelial carcinoma, and 48 (94%) of 51 serous carcinomas (P<0.001). In contrast, the frequency of IMP3 expression was significantly lesser in nonserous malignancies with 0 (0%) of 35, 5 (7%) of 70, 0 (0%) of 8, 3 (25%) of 12, and 5 (33%) of 15 positive expression rates in atypical hyperplasia or endometrial intraepithelial neoplasia, endometrioid, mucinous, clear cell carcinomas, and other malignancies, respectively. The IMP3 staining was
Kaliaperumal, Subashini; Deb, Amit Kumar; Babu, K. Ramesh; Srinivasan, Renuka
We report a case of bimatoprost induced serous macular detachment and choroidal folds following uneventful cataract surgery. A 66-year-old male using topical bimatoprost in both eyes for open angle glaucoma underwent uneventful cataract surgery in the right eye. Postoperatively, he was restarted on topical bimatoprost and antibiotic-steroids combination drops. One week after surgery, he presented with conjunctival hyperemia, serous macular detachment, and choroidal folds at the posterior pole. Fundus fluorescein angiography showed perifoveal leaks in early stage with pooling of dye in late stage. Discontinuation of bimatoprost led to resolution of serous detachment and choroidal folds within 3 weeks with significant improvement in visual acuity. Occurrence of serous macular detachment and choroidal folds in this case could be probably related to the proinflammatory property of bimatoprost. Hence, it should be used with caution in the immediate postoperative period after cataract surgery. PMID:27957367
Lim, Diana; Murali, Rajmohan; Murray, Melissa P.; Veras, Emmanuela; Park, Kay J.; Soslow, Robert A.
Aims Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Methods Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): i) squamous metaplasia; ii) endometriosis; iii) adenofibromatous background; and iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Results Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years and 75% of patients were younger than 60 years. 92% presented with disease confined to the pelvis and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high-grade (grade 3 out of 3). 80% of cases had at least 1 CEF and 59% had at least 2 CEFs. 11% overexpressed p16, 0% overexpressed p53 and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were re-classified as serous carcinoma (OSC). The median patient age was 54.5 years and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one-half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular
Yang, Dong; Eliott, Dean
Central serous chorioretinopathy (CSCR) is a challenging disease characterized by subretinal serous fluid accumulation. The complex pathogenesis is still not fully understood, but is thought to be multifactorial and involves exogenous and endogenous factors affecting the choroid and retinal pigment epithelium. The involvement of corticosteroids is undisputed, while the contribution of mineralocorticoid pathways is under investigation. This review addresses the proposed pathogenesis models and the evidence for systemic treatment of CSCR with mineralocorticoid antagonists.
Zhou, Jun; Zeng, Yu-Rong; Lin, Xiao-Feng; Min, Jun
Purpose. To report the clinical features and CT manifestations of giant pancreatic serous cystadenoma (≥10 cm). Methods. We retrospectively reviewed the clinical features and CT findings of 6 cases of this entity. Results. All 6 patients were symptomatic. The tumors were 10.2 cm–16.5 cm (median value, 13.0 cm). CT imaging revealed that all 6 cases showed microcystic appearances (n = 5) or mixed microcystic and macrocystic appearances (n = 1). Five patients with tumors at the distal end of the pancreas received distal pancreatectomy. Among these 5 patients, 2 patients underwent partial transverse colon resection or omentum resection due to close adhesion. One patient whose tumor was located in the pancreatic head underwent pancreaticoduodenectomy; however, due to encasement of the portal and superior mesenteric veins, the tumor was incompletely resected. One patient had abundant draining veins on the tumor surface and suffered large blood loss (700 mL). After 6–49 months of follow-up the 6 patients showed no tumor recurrence or signs of malignant transformation. Conclusions. Giant pancreatic serous cystadenoma necessitates surgical resection due to large size, symptoms, uncertain diagnosis, and adjacent organ compression. The relationship between the tumors and the neighboring organs needs to be carefully assessed before operation on CT image. PMID:27610132
Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor; Recurrent Ovarian Carcinoma; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Ovarian Cancer; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Ovarian Cancer
Sansone, Lori A.
Individuals with borderline personality disorder are diagnostically and clinically characterized by self-harm behavior, as indicated by the criterion in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, “recurrent suicidal behavior, gestures, or threats, or self-mutilating behavior.” However, individuals with borderline personality disorder can display externalized aggressive behavior, as well. In an area characterized by considerably less research, empirical evidence indicates that individuals with borderline personality disorder may exhibit physical violence toward partners, physical violence toward known but nonintimate individuals, criminal behaviors that embody externalized violence (e.g., property damage), and, on very rare occasion, murderous behavior (either of family members or anonymous others through serial killing). Given this under-researched area, there are probably other types of externalized aggressive behaviors that have not been empirically revealed. However, externalized aggressive behaviors in individuals with borderline personality disorder clearly exist and need to be assessed in both psychiatric and primary care settings in an effort to promote safety of medical personnel and effective patient management. PMID:22567607
Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide
Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery. We performed diagnostic laparoscopic surgery in order to make a correct diagnosis based on the histological tissue. The vermiform appendix was found to contain a tumor measuring 1.5 cm wide and 4.5 cm long. Laparoscopic appendectomy, partial omentectomy, and partial resection of the lesion in the peritoneum were performed. The histological diagnosis was mucinous adenocarcinoma of the vermiform appendix, and the stage was T4NxM1. The patient received adjuvant chemotherapy with mFOLFOX 6 (5FU, leucovorin, and oxaliplatin). She achieved stable disease and was alive with disease eleven months after surgery. We therefore recommend that gynecologists should not rule out the possibility of appendiceal cancer, even in cases with preoperative findings similar to those of serous papillary adenocarcinoma of the peritoneum with peritoneal disseminated tumors. PMID:24383020
Erickson, Britt K.; Kinde, Isaac; Dobbin, Zachary C.; Wang, Yuxuan; Martin, Jovana Y.; Alvarez, Ronald D.; Conner, Michael G.; Huh, Warner K.; Roden, Richard B.S.; Kinzler, Kenneth W.; Papadopoulos, Nickolas; Vogelstein, Bert; Diaz, Luis A.; Landen, Charles N.
Objective To investigate if tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon. Methods Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon prior to surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA. Results Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60%) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01–0.07%. Conclusion In this pilot study, DNA derived from tumor was detected in the vagina of 60% of ovarian cancer patients with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease. PMID:25437714
Idrees, Romana; Din, Nasir Ud; Fatima, Saira; Kayani, Naila
Uterine serous carcinoma (USC) is a rare variant of endometrial cancer that is not related to increased estrogen level; rather, it arises in a background of atrophic endometrium. Our aim was to describe clinicopathologic features of 4 cases of USC arising in endometrial polyps (EPs). The mean age of the patients at presentation was 53 years (range, 50-61 years). All patients presented with postmenopausal bleeding. In 3 patients, endometrial curretings were done before surgery, which was reported as EP with superficial foci of USC, EP with few clusters of atypical cells, and high-grade serous carcinoma, respectively. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and omental sampling. The uterine cavity showed an EP in all cases ranging in size from 2 to 3.5 cm (mean, 3 cm). The hysterectomy specimens revealed USC in EP as well as the adjacent endometrium in 3 patients. The nonneoplastic endometrium was atrophic in all cases. Residual tumor was not found in the endometrium in 1 case. Omental metastatic deposits were found in all cases. Tumor deposits were also seen in the serosa of uterus, fallopian tubes, and parametrium in 1 case. Two patients died of disease 2 years after diagnosis. The remaining 2 patients are alive after a follow-up of 3 years, respectively. In conclusion, USC is a rare aggressive tumor, and to establish the diagnosis, it is important to look for the small foci of the tumor in the atrophic endometrium and on the surface of the polyps as these patients are likely to harbor additional disease in the uterus or extrauterine sites. The postmenopausal group is at high risk for developing these tumors; therefore, all the endometrial biopsies/curettings and the EPs in this age group should be thoroughly sampled.
Dansingani, Kunal K; Balaratnasingam, Chandrakumar; Mrejen, Sarah; Inoue, Maiko; Freund, K Bailey; Klancnik, James M; Yannuzzi, Lawrence A
To describe a series of patients exhibiting annular retinal pigment epithelial (RPE) lesions in the context of chronic central serous chorioretinopathy. Retrospective comparative case series. Consecutive patients with chronic central serous chorioretinopathy were identified from the clinical practices of 3 retina specialists. A subset of patients exhibiting annular RPE lesions on fundus autofluorescence was included for chart review and examination of multimodal imaging (study group). Patients with alternative etiologies for neurosensory detachment or pigment epitheliopathy were excluded. A second consecutive cohort of patients, with acute central serous chorioretinopathy, was also examined for the presence of annular lesions (comparative group). Sixty-seven patients with chronic central serous chorioretinopathy were identified. Fourteen eyes of 12 patients exhibited annular lesions (study eyes). Mean visual acuity of study eyes was 20/27 (logMAR 0.13, SD 0.11). Annular lesions were composed of hyperautofluorescent stellate lesions arranged in an open or closed ring with intervening foci of punctate hypoautofluorescence. Optical coherence tomography showed RPE hyperplasia at the perimeters of annular lesions with loss of ellipsoid reflectivity and preserved RPE at the lesion center. Annular lesions were confined to the posterior poles and appeared to have developed at the margins of chronic neurosensory detachment. Forty-three eyes of 30 patients with acute central serous chorioretinopathy comprised the comparative group and none of these eyes exhibited annular lesions. Annular lesions occur in up to a fifth of patients with chronic central serous chorioretinopathy but carry a relatively good visual prognosis. Curvilinear RPE figures and demarcation lines are seen in various retinal conditions but the characteristics of annular lesions described here suggest that they are specific to chronic central serous chorioretinopathy. Copyright © 2016 Elsevier Inc. All
Morrison, Jane C; Blanco, Luis Z; Vang, Russell; Ronnett, Brigitte M
A precursor for invasive ovarian/pelvic high-grade serous carcinoma, termed serous tubal intraepithelial carcinoma (STIC), has been identified and characterized through careful analysis of the fallopian tubes in both prophylactic salpingo-oophorectomy specimens obtained from women with either a family history of breast and/or ovarian cancer or germline mutations of BRCA1 and BRCA2 and in cases of pelvic high-grade serous carcinoma. Data on incidental STICs and clinically occult microscopic invasive high-grade serous carcinomas are limited. We analyzed the clinicopathologic features of 22 cases, including 15 pure STICs and 7 STICs associated with microscopic invasive high-grade serous carcinomas, identified incidentally in fallopian tubes removed for nonprophylactic indications. Patient age ranged from 39 to 79 years (mean: 62.7; median: 61), with only 1 patient under the age of 50. No patients were known to carry BRCA1 or BRCA2 mutations. Of the 12 pure STICs for which the location in the fallopian tube could be established, 9 were in the fimbriated portion, 1 was at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. Of the 7 STICs with associated invasive high-grade serous carcinoma, 3 were located in the fimbriated portion, 2 were at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. The invasive components were in the fallopian tube in 6 cases, 4 in subepithelial stroma of tubal mucosa, and 2 as an intramucosal (exophytic) luminal lesion without invasion of underlying subepithelial stroma (size range: 1 to 4 mm). The remaining case had a microscopic focus of high-grade serous carcinoma within the ipsilateral ovary (1.3 mm cortical focus) identified only on deeper sections, without an associated invasive component in the fallopian tube. The preferential finding of atypical epithelium with the cytologic features of high-grade serous carcinoma, namely STIC, in the fallopian tubes rather than the
MIURA, MASAHIRO; ELSNER, ANN E.; WEBER, ANKE; CHENEY, MICHAEL C.; OSAKO, MASAHIRO; USUI, MASAHIKO; IWASAKI, TAKUYA
PURPOSE To evaluate a noninvasive technique to detect the leakage point of central serous chorioretinopathy (CSR), using a polarimetry method. DESIGN Prospective cohort study. METHODS SETTING Institutional practice. PATIENTS We examined 30 eyes of 30 patients with CSR. MAIN OUTCOME MEASURES Polarimetry images were recorded using the GDx-N (Laser Diagnostic Technologies). We computed four images that differed in their polarization content: a depolarized light image, an average reflectance image, a parallel polarized light image, and a birefringence image. Each polarimetry image was compared with abnormalities seen on fluorescein angiography. RESULTS In all eyes, leakage area could be clearly visualized as a bright area in the depolarized light images. Michelson contrasts for the leakage areas were 0.58 ± 0.28 in the depolarized light images, 0.17 ± 0.11 in the average reflectance images, 0.09 ± 0.09 in the parallel polarized light images, and 0.11 ± 0.21 in the birefringence images from the same raw data. Michelson contrasts in depolarized light images were significantly higher than for the other three images (P < .0001, for all tests, paired t test). The fluid accumulated in the retina was well-visualized in the average and parallel polarized light images. CONCLUSIONS Polarization-sensitive imaging could readily localize the leakage point and area of fluid in CSR. This may assist with the rapid, noninvasive assessment of CSR. PMID:16376644
Miura, Masahiro; Elsner, Ann E; Weber, Anke; Cheney, Michael C; Osako, Masahiro; Usui, Masahiko; Iwasaki, Takuya
To evaluate a noninvasive technique to detect the leakage point of central serous chorioretinopathy (CSR), using a polarimetry method. Prospective cohort study. Institutional practice. We examined 30 eyes of 30 patients with CSR. Polarimetry images were recorded using the GDx-N (Laser Diagnostic Technologies). We computed four images that differed in their polarization content: a depolarized light image, an average reflectance image, a parallel polarized light image, and a birefringence image. Each polarimetry image was compared with abnormalities seen on fluorescein angiography. In all eyes, leakage area could be clearly visualized as a bright area in the depolarized light images. Michelson contrasts for the leakage areas were 0.58 +/- 0.28 in the depolarized light images, 0.17 +/- 0.11 in the average reflectance images, 0.09 +/- 0.09 in the parallel polarized light images, and 0.11 +/- 0.21 in the birefringence images from the same raw data. Michelson contrasts in depolarized light images were significantly higher than for the other three images (P < .0001, for all tests, paired t test). The fluid accumulated in the retina was well-visualized in the average and parallel polarized light images. Polarization-sensitive imaging could readily localize the leakage point and area of fluid in CSR. This may assist with the rapid, noninvasive assessment of CSR.
Kapetanios, A D; Donati, G; Bouzas, E; Mastorakos, G; Pournaras, C J
The exact pathogenic mechanism of the accumulation of subretinal fluid at the posterior pole of the fundus in cases of central serous chorioretinopathy (CSC) is not well established. Recently, it was reported that CSC is more frequent among patients with endogenous Cushing's syndrome. Thus, it has been suggested that glucocorticoids might be involved in the pathogenesis of CSC. Subsequently, additional observations, have confirmed the relationship between glucocorticoids and CSC. We present preliminary data on the endogenous cortisol secretion in patients with CSC. Sixteen patients (14 men and 2 women, 35-65 years of age) suffering from CSC, not exposed to exogenous glucocorticoids and without clinical and/or biological stigmata of endogenous Cushing's syndrome, have been examined. Twenty four hour urinary free cortisol (24 h-UFC) secretion was measured within one week of their CSC episode. Twenty four hour urinary free cortisol of age and sex matched controls were also measured. Twenty four hour urinary free cortisol was 188.20 nmol/l +/- 34.1 for the patients suffering from CSC and 115.3 nmol/l +/- 63.4 for the control group (p < 0.05). These results give additional evidence that glucocorticoids may play a role in the pathogenesis of CSC. However, given the substantial variability of urinary free cortisol levels, as indicated by the increased SD, additional number of patients should be examined.
He, Shu-rong; Peng, Wei-xiang; Sun, Ming-jun; Yang, Li; He, Lei; Su, Xi-lai; He, Qing; Liu, Dong-ge
To evaluate the value of cytomorphologic and immunocytochemical approaches in the diagnosis of hematologic neoplasms in serous effusion. The cytospin and Thinprep smears of effusion specimens were prepared from 23 cases of lymphoid malignancies with histological confirmation and 30 cases of benign effusions used as control. Morphological assessment of the cellular components was conducted, including the ratio of mesothelium to lymphocyte, karyomorphism of lymphoid cell and the presence of apoptosis and mitosis. Immunocytochemical study was performed in all the cases, with flow cytometry in one case. Among the 23 tumor cases, 14 represented disease relapse, and in the remaining nine cases, the serous effusion was the primary manifestation. The proportion of mesothelium was low in the tumor group, being less than 10% in 20 cases (87.0%, 20/23). It was more than 10% in most of benign cases (20/30, 66.7%). Lymphoid cells were prominent (> 80% cells) in 69.6% of the tumor cases, and the cellular component in some control cases (63.3%, 19/30) showed fewer lymphocytes. Nipple-like projection of lymphocytic nuclei could be detected in almost all the tumor cases (91.3%, 21/23), but was occasionally found in the control group (26.7%, 8/30). Apoptosis and mitosis were obvious in lymphomatous effusion, but observed in only 6.7% of the control cases. Significant difference of the previously mentioned cytomorphologic features existed between the tumor and control groups (P < 0.01). The results of immunocytochemical staining in cell block were identical to the corresponding immunohistochemistry, and one case of mantle cell lymphoma was confirmed by flow cytometry. The cytologic findings seen in all the 23 studied cases were in agreement with the corresponding histologic diagnosis. Some cytomorphologic features, including decreased number of mesothelium, increased number of lymphoid cells, nuclear nipple-like projection, and the presence of apoptosis and mitosis, are very useful
Bromley, Amy B; Altman, Alon D; Chu, Pamela; Nation, Jill G; Nelson, Gregg S; Ghatage, Praful; Kalloger, Steve E; Han, Guangming; Köbel, Martin
We describe the architectural patterns of advanced ovarian/pelvic high-grade serous carcinomas that have been treated with upfront surgery, followed by adjuvant chemotherapy or neoadjuvant chemotherapy, followed by interval debulking to explore the association with the chemotherapeutic response. For 70 cases of advanced (i.e. stage III/IV) high-grade serous carcinomas (33 platinum resistant/intermediate, 37 platinum sensitive; 24 neoadjuvantly treated, 44 primary surgery), all tumor-containing histologic slides were reviewed by 1 of 3 pathologists. Histologic type was confirmed and the following features were assessed: major architectural pattern and the presence of any of 8 predefined minor architectural patterns (papillary, transitional cell carcinoma-like, micropapillary, microcystic, nested papillary, slit-like, glandular, solid). A semiquantitative assessment of psammoma bodies, histiocytic response, necrosis, nuclear atypia, and single-cell invasion was performed. Mitotic count was performed in 10 HPF and 1 HPF was counted for intraepithelial lymphocytes. The morphologic features were tested for an association with previous neoadjuvant chemotherapy and response to chemotherapy (resistant/intermediate versus chemotherapy-sensitive cases stratified by neoadjuvant chemotherapy), which was carried out using χ tests for categorical variables and analysis of variance for continuous data. Combinations of features were analyzed using unsupervised clustering (Wald). Although 8 of 18 features were significantly different when samples from neoadjuvantly treated patients were compared with those not previously treated, no individual histomorphologic feature or a combination of features was associated with response to chemotherapy. Further subtyping of high-grade serous carcinomas will likely need ancillary molecular markers that may have a greater potential to identify cases that will not respond to platinum-based chemotherapy.
Qian, Yushen; Pollom, Erqi L; Nwachukwu, Chika; Seiger, Kira; von Eyben, Rie; Folkins, Ann K; Kidd, Elizabeth A
Emerging evidence suggests that extent of lymphovascular space invasion (LVSI) predicts for risk of lymph node metastasis in endometrioid uterine cancers. However, this correlation remains unknown in the setting of uterine serous carcinoma (USC). We sought to examine the association between extent of LVSI and other histopathologic characteristics with risk of nodal metastasis for women with USC. Pathological data from all cases of uterine serous carcinoma between July 1998 to July 2015 at our institution were reviewed. Descriptive, univariate, and multivariate logistic regression analysis of selected pathologic features were performed. 88 patients with USC underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy. Surgical staging revealed the following FIGO stage distributions: I (41%), II (8%), III (32%), IV (19%). LVSI was present in 44 (50%) patients. 36 patients (41%) had LN metastases with median number of total nodes removed of 17 (range, 1-49). On univariate analysis, depth of myometrial invasion, LVSI, tumor size, and cervical stromal involvement were significantly associated with nodal involvement. In a multivariate model, LVSI (OR 6.25, 95% CI 2.2-18.0, p<0.01) and cervical stromal involvement (OR 3.33, 95% CI 1.10-10.0, p=0.03) were the only factors that remained significant. Among patients with LVSI-positive disease, extensive LVSI was associated with increased risk of nodal involvement compared to focal LVSI (90% vs 29%, p=0.04). Presence and extent of LVSI, and cervical stromal invasion are important predictors for lymph node metastasis in uterine serous carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.
Zanarini, M C; Frankenburg, F R; Khera, G S; Bleichmar, J
In this study, we describe the types and amounts of psychiatric treatment received by a well-defined sample of borderline personality disorder (BPD) inpatients, and compare these parameters with those of a group of carefully diagnosed personality-disordered controls. Finally, we assess the risk factors associated with a history of intensive, high-cost treatment, which we defined as having had two or more prior psychiatric hospitalizations. The treatment histories of 290 borderline inpatients and 72 axis II controls were assessed using a reliable semistructured interview. All nine forms of treatment studied except electroconvulsive therapy (ECT) were common among borderline patients (36% to 96%). In addition, a significantly higher percentage of borderline patients than axis II controls reported a history of individual and group therapy, day and residential treatment, psychiatric hospitalization, participating in self-help groups, and taking standing medications. They were also significantly younger when they first entered individual therapy and began to take standing medications. In addition, borderline patients spent more time than axis II controls in individual therapy and psychiatric hospitals, and were on standing medications for a significantly longer period of time. They also reported a significantly higher number of psychiatric hospitalizations, lifetime number of standing medications, and number of psychotropic medications taken at the same time. In addition, we found a highly significant multivariate predictive model for multiple prior hospitalizations. The six significant predictors were age 26 or older, a history of quasi psychotic thought, lifetime number of self-mutilative efforts and suicide attempts, a childhood history of reported sexual abuse, and an adult history of being physically and/or sexually assaulted. Taken together, these results confirm clinical impressions concerning the high rates of mental health services used by borderline patients
Beksac, Kemal; Irkkan, Cigdem; Argun, Guldeniz; Cetin, Bahadir
A 72-year-old woman presented with a mass on the right axilla. This was thought to be an occult breast cancer case, and the patient was treated with modified radical mastectomy, followed by hormonotherapy. Two years later she presented with incarcerated umbilical hernia. Pathology revealed Sister Mary Joseph's nodule inside the hernia sac. Further evaluation revealed that the primary tumor was papillary serous carcinoma of the peritoneal surface. The patient received adjuvant chemotherapy. Two years later the metastatic tumor was located on the other breast. The disease progressed gradually, and the patient eventually died from disseminated disease. This case is extraordinary in that it first presented with axillary metastasis without abdominal involvement and then later metastasized to the other breast after a long disease-free period.
Pich, Achille; Galliano, Diego
A 44-year-old man presented with painless right scrotal swelling of 2 years duration. A cystic tumor strictly attached to the head of the epididymis was surgically resected. The pathologic examination revealed a unilocular cyst with a thin fibrous capsule, lined by ciliated cubical or cylindrical columnar cells, mostly arranged in a single layer. No papillary projection could be detected. Immunohistochemical staining was positive for epithelial membrane antigen, low- and high molecular weight cytokeratins, progesterone receptor, vimentin, and S-100 protein, but was negative for carcinoembryonic antigen, CD10, p53 protein, and calretinin. Single MIB-1 positive cells were noted. Histologic and immunohistochemical features suggest a Müllerian origin or differentiation. The lesion was diagnosed as pure serous cystadenoma of the epididymis, possibly originating from vestigial remnants of the Müller duct in male. The differential diagnosis to spermatocele and adenomatoid tumor of the epididymis is discussed.
Background. Malignant neoplasms arising in Meckel's diverticulum, a vitelline duct remnant, are rare yet well-documented. Case Presentation. A 53-year-old previously healthy female presented with an enlarging midline abdominal wall mass. A computed tomography scan revealed a mass involving the linea alba, bilateral rectus abdominis, and subcutaneous fat. Extensive clinical workup failed to demonstrate other lesions, except local and paratracheal/hilar lymphadenopathy. Histopathologic examination of the resected tumor demonstrated a spectrum of serous neoplasia including serous cystadenoma, papillary serous carcinoma with numerous Psammoma bodies, and a poorly differentiated component. Immunophenotypically, the tumor cells were strongly positive for CK7, CK19, CA19.9, and MUC1 but negative for other lineage markers, findings suggestive of pancreatobiliary type differentiation. The patient died of the disease one year after the initial presentation despite chemotherapy, radiation, and surgery. Conclusion. We present a case of adenocarcinoma arising from the anterior midline abdominal wall, from presumed vitelline duct remnant, with histologic and immunophenotypic features of serous cystadenocarcinoma of pancreatobiliary origin. Though the origin from vitelline duct remnant is difficult to prove in this single case, understanding tumorigenesis of embryonic remnant origin is potentially important to improve the management of cancer of unknown primary. PMID:27999702
BRODIE, FRANK L.; CHARLSON, EMILY S.; ALEMAN, TOMAS S.; SALVO, REBECCA T.; GEWAILY, DINA Y.; LAU, MARISA K.; FARREN, NEIL D.; ENGELHARD, STEPHANIE B.; PISTILLI, MAXWELL; BRUCKER, ALEXANDER J.
Purpose The purpose of this study was to determine if there is an association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). Methods Patients with CSCR without a history of steroid use or secondary retinal disease were matched based on age/gender/body mass index with control patients and administered the Berlin Questionnaire to assess for OSA risk. Patients were scored “OSA+” if they were at “high risk” on the Berlin Questionnaire or reported a previous OSA diagnosis. Rates of OSA+ were compared between the 2 groups, odds ratio and its 95% confidence interval was calculated using exact conditional logistic regression. Results Forty-eight qualifying patients with CSCR were identified. There were no statistically significant differences between the CSCR and control groups by age (mean = 55 years), gender (79% male), body mass index (mean = 28.2), history of diabetes, or hypertension. Within the CSCR group, 22 patients (45.8%) were OSA+ versus 21 control patients (43.8%) (difference = 2.1%; 95% confidence interval, −18.2% to 22.2%; exact odds ratio = 1.08, 95% confidence interval, 0.47–2.49; P = 1.00). Conclusion When compared with matched controls, patients with CSCR did not have statistically significant higher rates of OSA risk or previous diagnosis. This finding contrasts with previous work showing a strong association between the diseases. The divergence is likely due to our matching controls for body mass index, a significant risk factor for OSA. PMID:25127049
Roy, Avik Kumar; Padhy, Debananda
An 18-year-old male with 360 degree angle recession after blunt trauma in his right eye developed uncontrolled intraocular pressure (IOP) despite four antiglaucoma medications (AGM) with advancing disc damage. He underwent trabeculectomy with intraoperative mitomycin-c (MMC) application. There was an intraoperative vitreous prolapse which was managed accordingly. On post-surgery day 1, he had shallow choroidal detachment superiorly with non-recordable IOP. This was deteriorated 1 week postoperatively as choroidal detachment proceeded to serous retinal detachment. He was started with systemic steroid in addition to topical route. The serous effusions subsided within 2 weeks time. At the last follow up at 3 months, he was enjoying good visual acuity, deep anterior chamber, diffuse bleb, an IOP in low teens off any AGM and attached retina. This case highlights the rare occurrence of serous retinal detachment after surgical management of angle recession glaucoma.
Khng, C G; Yap, E Y; Au-Eong, K G; Lim, T H; Leong, K H
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with widespread manifestations including the eye. Central serous retinopathy (CSR) has been associated as a complicating event in SLE, although it is uncommon. We present a case series of four female Chinese SLE patients who developed CSR during the course of their systemic disease. All four presented clinically with typical CSR. Angiographic findings did not show evidence of choroidal ischaemia or delayed choroidal filling. Resolution of the serous retinal detachment occurred in all four patients. Recovery of vision was seen in three patients. The clinical outcome was similar to that occurring in the usual male population. Central serous retinopathy as a manifestation of SLE may be caused by various factors. These include SLE-associated choroidopathy, systemic hypertension, renal disease, retinal pigment epithelial dysfunction and glucocorticoid therapy.
Precursor Lesions of Ovarian Serous Carcinoma PRINCIPAL INVESTIGATOR: Robert Kurman, M.D...5a. CONTRACT NUMBER Elucidation of Molecular Alterations in Precursor Lesions of Ovarian Serous Carcinoma 5b. GRANT NUMBER W81XWH-09-1-0249...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS prevention, p53 mutations, high grade serous
Sansone, R A; Chu, J W; Wiederman, M W; Lam, C
According to the empirical literature, there are high rates of borderline personality disorder (BPD) among individuals with formal diagnoses of eating disorders, and high rates of eating disorders among individuals with BPD. In this study, we examined relationships between three eating disorder symptoms (i.e., binge eating, starving oneself, abusing laxatives) and borderline personality symptomatology according to two self-report measures (the borderline personality scale of the Personality Diagnostic Questionnaire-4 and the Self- Harm Inventory) in a sample of psychiatric inpatients (N=126) and in a sample of internal medicine outpatients (N=419). Each individual eating disorder item, as well as a composite score of all three items, demonstrated statistically significant correlations with both measures of borderline personality symptomatology in both samples. In addition, endorsement of all three symptoms was invariably associated with borderline personality symptomatology on both measures. Specific eating disorder symptoms, alone, may predict for borderline personality symptomatology.
abnormal transudation of fluid and the subscquent serous detachment of the retinal pigment epltne- lium and the retina (12). The etiology of this...serves to shorten the course of the detachment (1,2,12,16,27,28, 31,42,46,51,52,54,56). Only two papers have dealt with ICSC in flyers. One is a 1972...25,%) nad active disease on initial evaluation as manitested by a leak on fluorescein angiography and/or serous detachment . Twenty-tour out - of fifty
Frank, H; Paris, J
To test psychodynamic hypotheses about the etiology of the borderline syndrome, female borderline patients were asked whether they remembered their mothers and fathers as having responded with approval, disinterest, or criticism to dependent and independent behaviors. Comparisons were made with a group of normal controls and with a group of neurotics and patients with personality disorders. The main finding was that borderline patients remembered their fathers as neglectful. The recollections did not support an overprotection hypothesis.
Slucki, Daniel; Wikinski, Mariana
A bibliographic review of the last year's psychoanalytic literature on borderline personality is presented. We expose diagnostic considerations, with special emphasis on those which refer to the boundaries between borderline personality, neurosis and psychosis on one hand, and those which distinguish between borderline personality and narcissistic disorders on the other. Vicissitudes of these patient's object relationships, their bond with other significant persons, their main psychic mechanisms, clinical traits and technical difficulties in the treatment are also described.
Eskander, Jonathan P.; Kuris, Eren O.; Younghein, Andrew J.; Landsman, Samuel; Japko, Leonard; Eskander, Mark S.
Study Design Case report. Objective This case exemplifies the importance of a high index of suspicion when dealing with intractable pain and neurologic symptoms in patients with a history of cancer. Fallopian tube cancer is relatively uncommon, accounting for less than 0.2% of all female malignancies. Because of a low index of suspicion, it is often detected at an advanced stage. From an orthopedic perspective, osseous metastasis from primary fallopian tube malignancies is rare with only a few documented cases in the medical literature. Methods This case report documents a 68-year-old woman who developed back pain and leg weakness after undergoing surgical resection with adjuvant therapy of a primary fallopian tube adenocarcinoma. Her hospital course and follow-up are documented. Results Imaging revealed a compression fracture in the L1 vertebral body that when a biopsy confirmed a soft tissue diagnosis of a high-grade serous papillary adenocarcinoma of fallopian tube origin. The patient underwent a surgical decompression, posterior stabilization, and tumor debulking with postoperative resolution of her symptoms. Conclusions This is the first reported case of a spine metastasis from a fallopian tube serous carcinoma in a living patient. This case documents the diagnosis of a pathologic vertebral fracture due to metastasis of an atypical cancer. PMID:26430604
Background Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Methods Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. Results The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function. Conclusions The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome. PMID:22967087
Kim, Jaeyeon; Coffey, Donna M; Ma, Lang; Matzuk, Martin M
Although named "ovarian cancer," it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53(R172H), into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53(R172H)-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice.
Sansone, Randy A; Sansone, Lori A
Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings-namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet's syndrome, somatic preoccupation, somatic. Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation.
ZANARINI, MARY C.; FRANKENBURG, FRANCES R.
The authors define a new defense mechanism, emotional hypochondriasis, that is hypothesized to be central to borderline psychopathology. The behavioral manifestation of this defense—the hyperbolic stance of the borderline patient—is also defined and related to the complex phenomenology of borderline personality disorder. Borderline patients are seen as making an active attempt to maintain a tolerable, if tenuous, adaptation in the face of tremendous subjective emotional pain that has been shaped in large measure by traumatic childhood events that have never been validated. Twelve treatment implications and three expectable, if overlapping, stages of treatment stemming from the use of this defense and its behavioral sequelae are detailed. PMID:22700171
... excessively in the body. Normally, the body controls cell growth and division. New cells are created to replace ... room for healthy replacements. If the balance of cell growth and death is disturbed, a tumor may form. ...
Park, Hyun Jeong; Choi, Byung Ihn; Lee, Eun Sun; Park, Sung Bin; Lee, Jong Beum
Rapid advances in liver imaging have improved the evaluation of hepatocarcinogenesis and early diagnosis and treatment of hepatocellular carcinoma (HCC). In this situation, detection of early-stage HCC in its development is important for the improvement of patient survival and optimal treatment strategies. Because early HCCs are considered precursors of progressed HCC, precise differentiation between a dysplastic nodule (DN), especially a high-grade DN, and early HCC is important. In clinical practice, these nodules are frequently called "borderline hepatic nodules." This article discusses radiological and pathological characteristics of these borderline hepatic nodules and offers an understanding of multistep hepatocarcinogenesis by focusing on the descriptions of the imaging changes in the progression of DN and early HCC. Detection and accurate diagnosis of borderline hepatic nodules are still a challenge with contrast enhanced ultrasonography, CT, and MRI with extracellular contrast agents. However, gadoxetic acid-enhanced MRI may be useful for improving the diagnosis of these borderline nodules. Since there is a net effect of incomplete neoangiogenesis and decreased portal venous flow in the early stage of hepatocarcinogenesis, borderline hepatic nodules commonly show iso- or hypovascularity. Therefore, precise differentiation of these nodules remains a challenging issue. In MRI using hepatobiliary contrast agents, signal intensity of HCCs on hepatobiliary phase (HBP) is regarded as a potential imaging biomarker. Borderline hepatic nodules are seen as nonhypervascular and hypointense nodules on the HBP, which is important for predicting tumor behavior and determining appropriate therapeutic strategies.
Coenegrachts, L; Garcia-Dios, D A; Depreeuw, J; Santacana, M; Gatius, S; Zikan, M; Moerman, P; Verbist, L; Lambrechts, D; Matias-Guiu, Xavier; Amant, Frédéric
Clinical outcome of 23 patients with mixed endometrioid and serous endometrial carcinomas (mixed EEC-SC) was compared to that of pure endometrioid (EEC) and pure serous (SC) carcinomas. Hotspot mutation frequencies in KRAS, PIK3CA, PTEN, and TP53 and microsatellite instability (MSI) status were determined in mixed EEC-SC, as well as in their EEC and SC microdissected components separately, and alterations were compared to frequencies in pure EEC and SC. Relapse-free (RFS) and overall survival (OS) differed significantly between mixed EEC-SC and pure EEC and SC, revealing that outcome of mixed EEC-SCs was intermediate to that of pure EEC and pure SC. PTEN mutations were absent in pure SC, but occurred in 20 % of pure EEC, and 13 % of mixed EEC-SC. In contrast, TP53 mutations were more frequent in pure SC (17 %) and mixed EEC-SC (22 %) than in pure EEC (2 %). Mutations in mixed EEC-SC were shared by the two microdissected components in 30 %, whereas in 35 %, some mutations were component-specific. Mutation analysis confirms similarities between the EEC and SC components of mixed EEC-SC with pure EEC and pure SC, respectively. However, PTEN and KRAS mutations were more frequent in the SC component of mixed EEC-SC than in pure SC, while TP53 mutations were more frequent in the EEC component of mixed EEC-SC than in pure EEC. Presence of different clonal mutation pattern between EEC and SC components of mixed EEC-SC raises the possibility of divergent tumor heterogeneity or biclonal origin in some cases.
Chapel, David B; Husain, Aliya N; Krausz, Thomas; McGregor, Stephanie M
Distinguishing malignant peritoneal mesothelioma (MPM) from serous carcinoma involving the peritoneum remains a diagnostic challenge, particularly in small biopsy and cytology specimens. In this distinction, PAX8 expression has been regarded as a specific marker of serous carcinoma. In addition, BAP1 loss is reportedly specific to MPM, in the distinction from both benign mesothelial lesions and ovarian serous tumors (OSTs). Using immunohistochemistry, we examined PAX8 and BAP1 expression in 27 MPMs, 25 cases of benign mesothelium, and 45 OSTs. Five MPMs were PAX8 (5/27, 18%), while 8 cases of benign mesothelium expressed PAX8 (8/25, 32%). PAX8 expression in mesothelium was significantly more common in women than in men (P=0.01). Sixteen MPMs exhibited BAP1 loss (16/25, 64%), while BAP1 was retained in all benign mesothelium and all OSTs. All cases of PAX8 mesothelium were negative for expression of estrogen receptor. These data show that PAX8 is expressed in both benign and malignant mesothelium, and that BAP1 loss is highly specific for MPM, in the differential with both benign mesothelial proliferations and OTSs. These results also have implications for primary diagnosis and for pathologic staging of OST. Caution should be applied when PAX8 expression is used to distinguish mesothelial and serous proliferations, and BAP1 loss may be confirmatory in cases where mesothelioma is favored.
The person with a borderline personality is considered to be neither neurotic nor psychotic, but to exist somewhere in between these two diagnostic categories. Psychoanalytic theorists who have researched the phenomenon of the borderline personality have shifted their emphasis away from Freud's instinct psychology and toward an ego psychology…
Johnson, Harriette C.
Reviews current research on treatment of borderline clients with medication, individual counseling, and family interventions. Notes that recent studies indicate that borderline personality is heterogeneous condition in which different underlying disorders (affective, schizotypal, and neurological) may be present. Reviews effectiveness of various…
Meehan, Kevin B; Panfilis, Chiara De; Cain, Nicole M; Antonucci, Camilla; Soliani, Antonio; Clarkin, John F; Sambataro, Fabio
The impact of borderline personality pathology on facial emotion recognition has been in dispute; with impaired, comparable, and enhanced accuracy found in high borderline personality groups. Discrepancies are likely driven by variations in facial emotion recognition tasks across studies (stimuli type/intensity) and heterogeneity in borderline personality pathology. This study evaluates facial emotion recognition for neutral and negative emotions (fear/sadness/disgust/anger) presented at varying intensities. Effortful control was evaluated as a moderator of facial emotion recognition in borderline personality. Non-clinical multicultural undergraduates (n = 132) completed a morphed facial emotion recognition task of neutral and negative emotional expressions across different intensities (100% Neutral; 25%/50%/75% Emotion) and self-reported borderline personality features and effortful control. Greater borderline personality features related to decreased accuracy in detecting neutral faces, but increased accuracy in detecting negative emotion faces, particularly at low-intensity thresholds. This pattern was moderated by effortful control; for individuals with low but not high effortful control, greater borderline personality features related to misattributions of emotion to neutral expressions, and enhanced detection of low-intensity emotional expressions. Individuals with high borderline personality features may therefore exhibit a bias toward detecting negative emotions that are not or barely present; however, good self-regulatory skills may protect against this potential social-cognitive vulnerability. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Ayache, Denis; Trabalzini, Franco; Bordure, Philippe; Gratacap, Benoit; Darrouzet, Vincent; Schmerber, Sébastien; Lavieille, Jean-Pierre; Williams, Marc; Lescanne, Emmanuel
To present a series of temporal en plaque meningiomas involving the middle ear or mastoid, whose main symptoms suggested a serous otitis media. Multicentric retrospective study reviewing clinical records originating from eight tertiary referral centers. The clinical records of 10 patients presenting with signs and symptoms suggesting serous otitis media and whose neuroimaging studies revealed a temporal en plaque meningioma involving the middle ear or mastoid are reported. All the patients were women, ranging from 49 to 71 years old. The delay between the onset of symptoms and the diagnosis of meningioma varied from 1 to 10 years. All the patients underwent various procedures usually applied for the treatment of serous otitis media, which failed in all the cases, particularly ventilating tube placement, which was followed by severe episodes of discharge. In all cases, the computed tomographic scans showed three imaging signs: soft tissue mass filling the middle ear or mastoid, hyperostosis of the petrous bone, and hairy aspect of the intracranial margins of the affected bone. This imaging triad must alert the otologist of the possibility of intracranial meningioma. Magnetic resonance imaging was the method of choice to assess the diagnosis of intracranial meningioma involving the middle ear or mastoid. When analyzing management options, it appeared that conventional middle ear procedures were inefficient. Temporal en plaque meningioma involving the middle ear or mastoid can mimic a serous otitis media. A computed tomographic scan is recommended for cases of atypical or prolonged unilateral serous otitis media to investigate indirect signs of a meningioma, which has to be confirmed with magnetic resonance imaging.
Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H; Zhang, Bai; McDermott, Jason E; Zhou, Jian-Ying; Petyuk, Vladislav A; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A; Clauss, Therese R; Choi, Caitlin; Monroe, Matthew E; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J; Yu, Kun-Hsing; Tabb, David L; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S; Hiltke, Tara; Rivers, Robert C; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P; Levine, Douglas A; Smith, Richard D; Chan, Daniel W; Rodland, Karin D
To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT.
Cardasis, W; Hochman, J A; Silk, K R
The relationship of possession of transitional objects to the borderline personality disorder diagnosis was explored in a psychiatric inpatient setting. It was hypothesized that a greater proportion of inpatients who bring objects of special meaning with them to the hospital have borderline personality disorder. Psychiatric inpatients (N = 146) were administered a semistructured interview to determine the presence of special (i.e., transitional) objects in the hospital, at home, or during childhood. Borderline personality disorder was determined by criteria on a DSM-III-R borderline personality disorder checklist and by DSM-III-R discharge diagnosis. Significantly more patients who endorsed having transitional objects in the hospital or at home had the diagnosis of borderline personality disorder. Sensitivity, specificity, positive predictive power, and negative predictive power of the possession of the transitional object for the borderline personality disorder diagnosis were calculated. Specificity was higher than sensitivity, and negative predictive power was higher than positive predictive power in each instance. While these results suggest that absence of a transitional object is more likely to be associated with absence of borderline personality disorder than the presence of a transitional object is with the presence of borderline personality disorder, the sensitivity of a transitional object during adulthood to predict a diagnosis of borderline personality disorder was 63%, and the positive predictive power was 45%. A transitional object brought to the hospital may help remind the inpatient with borderline personality disorder of home or provide soothing during separation from home. The persistence of transitional objects into adulthood may inform the therapist of possible transference paradigms that may develop in treatment.
Bachmayr-Heyda, Anna; Aust, Stefanie; Auer, Katharina; Meier, Samuel M; Schmetterer, Klaus G; Dekan, Sabine; Gerner, Christopher; Pils, Dietmar
Purpose: Cancer metabolism is characterized by alterations including aerobic glycolysis, oxidative phosphorylation, and need of fuels and building blocks.Experimental Design: Targeted metabolomics of preoperative and follow-up sera, ascites, and tumor tissues, RNA sequencing of isolated tumor cells, local and systemic chemokine, and local immune cell infiltration data from up to 65 high-grade serous ovarian cancer patients and 62 healthy controls were correlated to overall survival and integrated in a Systems Medicine manner.Results: Forty-three mainly (poly)unsaturated glycerophospholipids and four essential amino acids (citrulline) were significantly reduced in patients with short compared with long survival and healthy controls. The glycerophospholipid fingerprint is identical to the fingerprint from isolated (very) low-density lipoproteins (vLDL), indicating that the source of glycerophospholipids consumed by tumors is (v)LDL. A glycerophospholipid-score (HR, 0.46; P = 0.007) and a 100-gene signature (HR, 0.65; P = 0.004) confirmed the independent impact on survival in training (n = 65) and validation (n = 165) cohorts. High concentrations of LDLs and glycerophospholipids were independently predictors for favorable survival. Patients with low glycerophospholipids presented with more systemic inflammation (C-reactive protein and fibrinogen negatively and albumin positively correlated) but less adaptive immune cell tumor infiltration (lower tumor and immune cell PD-L1 expression), less oxygenic respiration and increased triglyceride biosynthesis in tumor cells, and lower histone expressions, correlating with higher numbers of expressed genes and more transcriptional noise, a putative neo-pluripotent tumor cell phenotype.Conclusions: Low serum phospholipids and essential amino acids are correlated with worse outcome in ovarian cancer, accompanied by a specific tumor cell phenotype. Clin Cancer Res; 23(8); 2081-92. ©2016 AACR.
Arole, Vidya Chandrakant; Deshpande, Kalpana Ananad; Jadhav, Dipashri Bhaurao; Jogi, Akash
Psammocarcinoma is a rare low-grade serous carcinoma arising either from ovary or peritoneum and is characterized by extensive psammomatous calcifications and invasion of surrounding structures. Prognostically, psammocarcinoma resembles borderline serous tumor and has a much more favorable outcome than the common serous carcinoma of ovary and peritoneum. © 2017 Japan Society of Obstetrics and Gynecology.
Expression of PH Domain Leucine-rich Repeat Protein Phosphatase, Forkhead Homeobox Type O 3a and RAD51, and their Relationships with Clinicopathologic Features and Prognosis in Ovarian Serous Adenocarcinoma
Zhang, Jun; Wang, Jun-Chao; Li, Yue-Hong; Wang, Rui-Xue; Fan, Xiao-Mei
Background: Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the differences in the PH domain leucine-rich repeat protein phosphatase (PHLPP), forkhead homeobox type O 3a (FoxO3a), and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. Methods: The PHLPP, FoxO3a, and RAD51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed. Results: In high-grade serous adenocarcinomas, the positive rates of PHLPP and FoxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). Meanwhile, in high-grade tumors, Stage III/IV tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors (43.5% and 36.0%) were significantly higher than in patients with PHLPP-negative tumors (5.6% and 7.2%, respectively; P < 0.05). Similarly, the 5-year survival rate of RAD51-positive patients (3.0%) was significantly lower than in negative patients (42.9%; P < 0.05). In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis. Conclusions: Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development
Szabova, Ludmila; Bupp, Sujata; Kamal, Muhaymin; Householder, Deborah B.; Hernandez, Lidia; Schlomer, Jerome J.; Baran, Maureen L.; Yi, Ming; Stephens, Robert M.; Annunziata, Christina M.; Martin, Philip L.; Van Dyke, Terry A.
The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value. We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53 and Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. Here, we describe an adaptation of these GEM models to orthotopic allografts that uniformly develop tumors with short latency and are ideally suited for routine preclinical studies. Ovarian tumors deficient in Brca1 respond to treatment with cisplatin and olaparib, a PARP inhibitor, whereas Brca1-wild type tumors are non-responsive to treatment, recapitulating the relative sensitivities observed in patients. These mouse models provide the opportunity for evaluation of effective therapeutics, including prediction of differential responses in Brca1-wild type and Brca1–deficient tumors and development of relevant biomarkers. PMID:24748377
Katabathina, Venkata S; Amanullah, Farhan S; Menias, Christine O; Chen, Melissa M; Valente, Philip T; Chintapalli, Kedar N; Prasad, Srinivasa R
The spectrum of extrauterine pelvic serous carcinomas includes ovarian serous carcinoma, primary peritoneal serous carcinoma, and primary fallopian tube carcinoma. Ovarian serous carcinoma, the most common ovarian malignant epithelial neoplasm, consists of two distinct entities: high-grade and low-grade serous carcinomas. Primary peritoneal serous carcinoma and primary fallopian tube carcinoma are rare malignancies that share many characteristics of high-grade serous carcinomas. Recent advances in the genetics and molecular biology of gynecologic cancers have suggested a common origin of many extrauterine pelvic serous carcinomas from fallopian tube epithelium. With the exception of low-grade serous carcinomas, which arise from cortical inclusion cysts lined by tubal epithelium, most extrauterine pelvic serous carcinomas are believed to originate from serous tubal intraepithelial carcinomas and show similar clinical-biologic behaviors and natural histories. Indeed, the International Federation of Gynecology and Obstetrics Committee on Gynecologic Oncology recently recognized that these cancers should be considered collectively, with a common system of staging and management strategies for ovarian, primary peritoneal, and fallopian tube cancers. A paradigm shift has occurred in our understanding of the pathogenesis of extrauterine pelvic serous carcinomas that has the potential to change current strategies for screening, prevention, diagnosis, and management. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging, and combined positron emission tomography and CT are pivotal in screening, initial diagnosis, and treatment follow-up; however, because of this paradigm shift, new radiologic techniques, such as contrast material-enhanced US and molecular US imaging, and various optical imaging techniques are being investigated as important screening and diagnostic tools. Because of evolving knowledge of genetic and molecular changes underlying the
Kar, Siddhartha P.; Tyrer, Jonathan P.; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K.; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K.; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain A.; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Phelan, Catherine M.; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston-Campbell, Lara E.; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Monteiro, Alvaro N. A.; Freedman, Matthew L.; Gayther, Simon A.; Pharoah, Paul D. P.
Background Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by co-expression may also be enriched for additional EOC risk associations. Methods We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly co-expressed with each selected TF gene in the unified microarray data set of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this data set were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Results Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P<0.05 and FDR<0.05). These results were replicated (P<0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. Conclusion We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Impact Network analysis integrating large, context-specific data sets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. PMID:26209509
Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain A; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston-Campbell, Lara E; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A; Monteiro, Alvaro N A; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P
Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. ©2015 American Association for Cancer Research.
Hong, Mun-Kun; Lee, Ming-Hsun; Ding, Dah-Ching; Chu, Sung-Chao; Chu, Tang-Yuan
This report describes a case of serous ovarian carcinoma with occult serous tubal intraepithelial carcinoma (STIC), which presented as atypical glandular cells favor neoplasia (AGC-FN) with Pap cytology and dermatomyositis. A 48-year-old woman presented with symptoms of dermatomyositis. An AGC-FN result from a Pap smear, with an absence of a cervical or endometrial lesion was noted. After cancer surveillance, ovarian high grade serous carcinoma associated with serous tubal intraepithelial carcinoma was diagnosed. Two weeks following surgical excision of the carcinoma, dramatic remission of the dermatomyositis symptoms was evident. The patient had serous carcinoma of the ovary with tubal STIC, which presented as dermatomyositis. The AGC-FN identified from a Pap smear hinted at a diagnosis of ovarian carcinoma. These presentations point to an occult malignancy in the genital tract and demand careful diagnostic workup. Copyright © 2015. Published by Elsevier B.V.
Sansone, Lori A.
Objective: Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings—namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. Data Sources: We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet’s syndrome, somatic preoccupation, somatic. Study Selection: Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. Results: According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Conclusions: Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation. PMID:26644960
Chen, Yu-Li; Chang, Ming-Cheng; Huang, Chia-Yen; Chiang, Ying-Cheng; Lin, Han-Wei; Chen, Chi-An; Hsieh, Chang-Yao; Cheng, Wen-Fang
The alpha-folate receptor (α-FR) is highly-expressed in various non-mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha-folate receptor (α-FR) and the clinico-pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of α-FR to chemo-resistance. Therefore, semi-quantitative reverse-transcription polymerase chain reactions for α-FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of α-FR in each ovarian cancer tissue specimen was defined as the ratio of density of α-FR to density of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In vitro apoptotic experiments were tested in the original OVCAR-3 tumor cells and various OVCAR-3 α-FR-transfectants. Patients with an increased α-FR expression level had poorer responses to chemotherapy (per α-FR expression level increase: odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40-57.36), p = 0.021). An increased α-FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per α-FR expression level increase: hazard ratio (HR): 2.45 (95% CI: 1.16-5.18), p = 0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per α-FR expression level increase: HR: 3.6 (95% CI: 0.93-13.29), p = 0.03) by multivariate analyses. α-FR inhibited cytotoxic drug-induced apoptosis in our in vitro apoptotic assays. α-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, α-FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment.
Gilbert, J W; Wolpin, B; Clancy, T; Wang, J; Mamon, H; Shinagare, A B; Jagannathan, J; Rosenthal, M
Diagnostic imaging plays a critical role in the initial diagnosis and therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the concept of 'borderline resectable' pancreatic cancer has emerged to describe a distinct subset of patients existing along the spectrum from resectable to locally advanced disease for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship of the primary tumor with surrounding vasculature. This review traces the conceptual evolution of borderline resectability from a radiological perspective, including the debates over the key imaging criteria that define the thresholds between resectable, borderline resectable, and locally advanced or metastatic disease. This review also addresses the data supporting neoadjuvant therapy in this population and discusses current imaging practices before and during treatment. A growing body of evidence suggests that the borderline resectable group of patients may particularly benefit from neoadjuvant therapy to increase the likelihood of an ultimately margin-negative (R0) resection. Unfortunately, anatomic and imaging criteria to define borderline resectability are not yet universally agreed upon, with several classification systems proposed in the literature and considerable variance in institution-by-institution practice. As a result of this lack of consensus, as well as overall small patient numbers and lack of established clinical trials dedicated to borderline resectable patients, accurate evidence-based diagnostic categorization and treatment selection for this subset of patients remains a significant challenge. Clinicians and radiologists alike should be cognizant of evolving imaging criteria for borderline resectability given their profound implications for treatment strategy, follow-up recommendations, and prognosis.
Devor, Eric J; Hovey, Adriann M; Goodheart, Michael J; Ramachandran, Shyam; Leslie, Kimberly K
microRNAs (miRNAs) control a multitude of pathways in human cancers. Differential expression of miRNAs among different histological types of tumors within the same type of tissue offers insight into the mechanism of pathogenesis and may help to direct treatment to improve prognosis. We assessed expression of 667 miRNAs in endometrial endometrioid and serous adenocarcinomas using RNA extracted from benign endometrium as well as from primary endometrial tumors. Quantitative miRNA profiling of endometrial adenocarcinomas revealed four overlapping groups of significantly overexpressed and underexpressed miRNAs. The first group was composed of 20 miRNAs significantly dysregulated in both adenocarcinoma types compared with benign endometrium, two groups were composed of miRNAs significantly dysregulated in either endometrioid adenocarcinomas or in serous adenocarcinomas compared with benign endometrium, and the fourth group was composed of 17 miRNAs that significantly distinguished between endometrioid adenocarcinomas and serous adenocarcinomas themselves. Validation of the expression levels of the selected miRNAs was carried out in a second panel composed of ten endometrioid and five serous tumors. Experimentally validated mRNA targets of these dysregulated miRNAs were identified using published sources, whereas TargetScan was used to predict targets of miRNAs in the first and fourth profile groups. These validated and potential miRNA target lists were filtered using published lists of genes displaying significant overexpression or underexpression in endometrial cancers compared to benign endometrium. Our results revealed a number of dysregulated miRNAs that are commonly found in endometrial (and other) cancers as well as several dysregulated miRNAs not previously identified in endometrial cancers. Understanding these differences may permit the development of both prognostic and diagnostic biomarkers.
Miše, Branka Petrić; Telesmanić, Vesna Dobrić; Tomić, Snježana; Šundov, Dinka; Čapkun, Vesna; Vrdoljak, Eduard
To analyze correlation between immunoexpression of E-cadherin and efficacy of first line platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma. The expression of E-cadherin was analyzed immunohistochemically in formalin-fixed, paraffin-embedded samples from 98 patients with advanced-stage high-grade serous ovarian cancer and related to clinical features (stage according to the International Federation of Gynecology and Obstetrics (FIGO) and residual tumors after initial cytoreductive surgery), response to platinum-based chemotherapy (according to Response Evaluation Criteria in Solid tumors (RECIST 1.1 criteria)), platinum sensitivity (according to platinum free interval (PFI) as platinum-refractory, platinum-resistant and platinum-sensitive) and patients progression free survival (PFS) and overall survival (OS). E-cadherin immunostaining was positive in 74 and negative in 24 serous ovarian carcinomas. E-cadherin immunoreactivity was not associated with FIGO stage, residual tumor after initial cytoreductive surgery and number of chemotherapy cycles. Positive E-cadherin expression predict significantly better response to first line platinum-based chemotherapy (p < 0.001) and platinum sensitivity (p < 0.001). Moreover, positive E-cadherin expression predict significantly longer PFS (p < 0.001) and OS (p < 0.001). The multivariate analysis for OS showed that positive E-cadherin expression is predictor to platinum sensitivity (p < 0.001) and longer OS (p = 0.01). Positive E-cadherin expression seems to be a predictor of better response to first line platinum-based chemotherapy, platinum sensitivity and favorable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative E-cadherin expression was shown to be significant, independent predictor of poorer PFS and OS. E-cadherin as a marker has predictive and prognostic value.
Kealy, David; Ogrodniczuk, John S
Individuals with borderline personality disorder (BPD) face considerable difficulties, both in terms of their symptom and functional status, as well as in attempting to obtain professional help. Their exclusion from appropriate mental health care and opportunities for recovery can be examined using the social construct of marginalization. Pervasive attitudes among clinicians, health care administrators, and policy-makers perpetuate the marginalization of BPD within systems of mental health care. Patients with BPD may be regarded as not suffering from a legitimate disorder, comprising a minority of the clinical population, and/or being a chronic drain on health care resources. Lack of suitable mental health services may be rationalized based on these attitudes. Considerable development in the empirical understanding of BPD challenges these stigmatizing attitudes and calls for critical questioning of the marginalized status of patients with BPD.
Stein, Dan J
Several psychiatric disorders, including borderline personality disorder (BPD), are characterized by emotional dysregulation and impulse dyscontrol. More specifically, symptoms in patients with BPD often occur within the context of disruptions in attachment and related distortions in cognitive-affective processing of the self and others. From a neurocircuitry perspective, findings include prefrontal hypoactivity, amygdala hyperreactivity, and alterations in prefrontal-limbic interaction. Molecular pathways relevant to these circuits include the serotonergic, noradrenergic, and dopaminergic systems, and there is some evidence that pharmacotherapy with agents that act on these systems may be useful. Given the disruptions in attachment and schemas of the self and others in BPD, establishing a therapeutic alliance is crucial while psychotherapy remains the cornerstone of an integrated approach to management.
Griffiths, Dorothy E.
Every family practice includes people who are difficult to manage. Persons with a borderline personality disorder can be the most difficult of all. They will trust no one, and consequently few, if any, others will be able to tolerate their profoundly difficult interpersonal communication style. These patients will present to their family physician more and more often with a variety of somatic and emotional symptoms. They will demand, either verbally or silently, that these symptoms be relieved immediately. This increasing demand for immediate response may eventually cause the physician to reject the patient. An understanding of this condition and how it develops in infancy may enable the physician to help the patient. A family physician who can set appropriate limits to the patient's demands may slowly convince the patient that he can trust and not be hurt. PMID:21248944
initial evaluation as manifested by a leak on fluorescein too - angiography and/or serous detachment . Out of 55 eyes 24 (44%) were seen within 6...Depth Perception, Amsler Grid, Fluorescin Angiography 19. ABSTRACT (Continue on reverse if necessary and identify by block number) INTRODUCTION...DIECKERT, M.D., and T. J. TREDICI, M.D. GREEN RP JR, CARLSON DW, DIECKERT JP, TREDICi TJ. Central cein angiography of the fundus in 1961, however, that
Chen, Ning; Yi, Xiaofang; Abushahin, Nisreen; Pang, Shujie; Zhang, Donna; Kong, Beihua; Zheng, Wenxin
Endometrial serous carcinoma (ESC) is the most aggressive subtype of endometrial cancer. Its aggressive behavior and poor clinical outcome may be partially attributed to lack of early diagnostic markers and unclear patho-genesis. The transcription factor Erythroid-E2-related factor 2 (Nrf2) is a recently identified protein marker, which plays a role in carcinogenesis as well as responsible for poor prognosis of many human cancers. The aim of this study is to determine the Nrf2 expression in benign endometrium (n=28), endometrial cancers (n=122) as well as their precursor lesions (n=81) trying to see whether Nrf2 has any diagnostic usage and is potentially involved in endometrial carcinogenesis. The level of Nrf2 was evaluated by immunohistochemical (IHC) and verified by using Western blots. Among the malignant cases, Nrf2 was positive in 28 (68%) of 50 ESCs, which was significantly more than in 3 (6%) of 50 endometrioid carcinomas (p < 0.001) and 2 (13%) of 15 clear cell carcinomas (p = 0.001) and other histologic types of endometrial cancers. Among endometrial precursor lesions, both serous endometrial glandular dysplasia (EmGD, 40%) and serous endometrial intraepithelial carcinoma (EIC, 44%) showed a significantly higher Nrf2 expression than that in atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (0%), clear cell EmGD (10%), and clear cell EIC (25%), respectively. We conclude that Nrf2 overexpression is closely associated with endometrial neoplasms with serous differentiation. Alteration of Nrf2 expression may represent one of the early molecular events in ESC carcinogenesis and overexpression of Nrf2 may used as a diagnostic marker in surgical pathology.
Hayes, Stephen J; Misfar, Nasira; Slade, Richard; Mamtora, Hari; Wilson, Godfrey
We describe the first reported case of extensive calcification seen in association with serous cystadenofibroma of the ovary, illustrating that calcification in the female genital tract may be extensive in nature, presenting in a fashion that is not entirely typical of dystrophic or metastatic calcification. This case demonstrates that extensive calcification within the pelvis should be interpreted with caution, as it may not represent disseminated malignancy.
Kocyigit, Murat; Ortekin, Safiye Giran; Cakabay, Taliye; Ozkaya, Guven; Bezgin, Selin Ustun; Adali, Mustafa Kemal
Introduction Otitis media with effusion is the fluid in the middle ear with no signs or symptoms of acute ear infection. Objective This study aims to research the frequency of serous otitis media in patients referred to the pediatric clinic between 3–16 years of age without any active ear, nose, and throat complaints. Methods This study included 589 children patients (280 boys, 309 girls; mean age: 9.42; range 3–16) who were administered to the pediatric clinic without otolaryngologic complaints. Patients underwent examination with flexible nasopharyngoscopy for adenoid hypertrophy. An otorhinolaryngologist examined all children on both ears using an otoscope and tested with tympanometry. We used tympanometry results to diagnose SOM. Results The study included 589 patients that underwent fiber optic examination of the nasopharynx with an endoscope. Adenoid vegetation was present in 58 patients (9.8%) and was not detected in 531 patients (90.2%). We found serous otitis media in 94 (15.9%) patients. We obtained Type A tympanogram in 47 (81%) of 58 patients with adenoid vegetation, 6 (10.3%) Type B, and 5 (8.6%) Type C. When comparing 58 patients with adenoid vegetation with 538 patients without adenoid vegetation for serous otitis media, the frequency was not statistically significant (p > 0.05). Conclusion We believe that in children without any ear, nose, and throat complaints, it is possible to detect serous otitis media with adenoid vegetation. Thus, pediatric patients should undergo screening at regular intervals. PMID:28382124
Shinojima, Ari; Mori, Ryusaburo; Fujita, Kyoko; Yuzawa, Mitsuko
Central serous chorioretinopathy (CSC), which has the characteristics of a serous retinal detachment (SRD) in the macular area, affects mostly men in the 30- to 50-yr age range. Some patients have persistent SRD, which may cause retinal thinning and photoreceptor impairment. CSC symptoms are gradual vision loss and/or metamorphopsia. Some commercial airline pilots are concerned about CSC symptoms, which can disqualify them from flying for months and can also reoccur. Thus, careful monitoring and treatment of CSC are critical for pilots, especially those with chronic or recurrent CSC. The Federal Aviation Administration requires uncorrected distant visual acuity in the better eye to be 20/200 or better, with correction to 20/20 or better employing lenses of no greater power than ± 3.5 diopters spherical equivalent. Multimodal imaging modalities such as spectral domain optical coherence tomography (SD-OCT) allow early detection of CSC noninvasively. Moreover, half-dose verteporfin photodynamic therapy (PDT) can cure CSC in the early stage. Five male Japanese commercial airline pilots with CSC are presented. Four of these five pilots had been disqualified from flying for several months, but after receiving half-dose PDT, they were ultimately able to resume flying commercial aircraft. Half-dose PDT can rapidly reduce serous subretinal fluid in CSC eyes. Recurrent and/or chronic CSC is seen in clinical cases. Therefore, continuous observation by SD-OCT after half-dose PDT is essential, even if the patient's vision recovers. Early, i.e., before visual acuity decreases, treatment is highly recommended.Shinojima A, Mori R, Fujita K, Yuzawa M. Treatment and monitoring of central serous chorioretinopathy in pilots. Aerosp Med Hum Perform. 2016; 87(12):1041-1044.
Gashi, A.A.; Borson, D.B.; Finkbeiner, W.E.; Nadel, J.A.; Basbaum, C.B.
To determine whether serous or mucous cells in tracheal submucosal glands respond to the neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP). The authors studied the peptide-induced changes in gland cell morphology accompanying release of TVSO4-labeled macromolecules from tracheal explants of ferrets. Explants were labeled for 1 h in medium containing TVSO4 and washed for 3.5 additional hours. Base-line secretion in the absence of drugs declined between 1.5 and 3.5 h after the pulse. Between 2.5 and 3.5 h, the average percent change in counts per minute recovered per sample period was not significantly different from zero. Substance P and VIP added 4 h after labeling each increased greatly the release of TVSO4-labeled macromolecules above base line. Bethanechol, a muscarinic-cholinergic agonist, increased secretion by an average of 142% above base line. Light and electron microscopy of the control tissues showed glands with narrow lumens and numerous secretory granules. Glands treated with SP or VIP had enlarged lumens and the serous cells were markedly degranulated. These phenomena were documented by morphometry and suggest that SP and VIP cause secretion from glands at least partially by stimulating exocytosis from serous cells.
was discussed. Dr. Soslow asked how to evaluate endometrial serous cancers if there is a lesion in the tubes and if peritoneal carcinoma was...received by all participants as well as from DoD OCRP staff. 15. SUBJECT TERMS prevention, p53 mutations, high grade serous ovarian cancer and STIC...ovarian cancer by characterizing the early lesions involved in the development of high-grade ovarian serous carcinoma, and 2) to provide biomarkers
Cevher, Selim; Sahinoglu-Keskek, Nedime; Unal, Fikret; Demirduzen, Selahaddin; Oksuz, Huseyin
32-year-old Turkish male patient presented with an optic disk pit and serous macular detachment in the left eye. Spectral domain optical coherence tomography revealed serous macular detachment and retinoschisis. After vitrectomy the retina gradually flattened and vision was gradually improved. We aimed to report a case of serous macula detachment secondary to optic pit and long term result of surgical treatment. PMID:26881159
Gunderson, John G.
Objective The purpose of this article is to describe the development of the borderline personality disorder diagnosis, highlighting both the obstacles encountered and the associated achievements. Method On the basis of a review of the literature, the author provides a chronological account of the borderline construct in psychiatry, summarizing progress in decade-long intervals. Results Borderline personality disorder has moved from being a psychoanalytic colloquialism for untreatable neurotics to becoming a valid diagnosis with significant heritability and with specific and effective psychotherapeutic treatments. Nonetheless, patients with this disorder pose a major public health problem while they themselves remain highly stigmatized and largely neglected. Conclusions Despite remarkable changes in our knowledge about borderline personality disorder, increased awareness involving much more education and research is still needed. Psychiatric institutions, professional organizations, public policies, and reimbursement agencies need to prioritize this need. PMID:19411380
Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.
Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.
Zanarini, Mary C.; Weingeroff, Jolie L.; Frankenburg, Frances R.
This study assessed the defensive functioning of 290 criteria-defined borderline patients and compared it to that of 72 patients with other forms of axis II psychopathology. The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was administered to 362 axis II inpatients diagnosed using semistructured interviews of proven reliability. Borderline patients had significantly higher scores than axis II comparison subjects on three of the four defense styles assessed by the DSQ: self-sacrificing, maladaptive action, and image-distorting defenses. They also had significantly higher scores than axis II comparison subjects on eight of the 19 defense mechanisms studied. More specifically, borderline patients had significantly higher scores on one neurotic-level defense (undoing), four immature defenses (acting out, emotional hypochondriasis, passive aggression, and projection), and two image- distorting/borderline defenses (projective identification and splitting). In contrast, axis II comparison subjects had a significantly higher score than borderline patients on one mature defense (suppression). When all significant defenses were considered together, three were found to be significant predictors of a borderline diagnosis: acting out, emotional hypochondriasis, and undoing. This model has both good sensitivity (.95) and positive predictive power (.86). Taken together, the results of this study suggest that the defensive profile of borderline patients is distinct from that of patients with other forms of axis II pathology. They also suggest that the defensive triad of acting out, emotional hypochondriasis, and undoing may serve as a useful clinical marker for the borderline diagnosis, particularly in settings where the base rate of the disorder is high. PMID:19379090
Patrono, Maria Guadalupe; Iniesta, Maria D; Malpica, Anais; Lu, Karen H; Fernandez, Rodrigo Orozco; Salvo, Gloria; Ramirez, Pedro T
OBJECTIVE. Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic (i.e., ovarian or peritoneal) high-grade serous carcinoma. The incidence of STIC has been reported to range from 0.6% to 7% in BRCA mutations carriers. However, the clinical outcome of patients with 'isolated' STIC remains elusive. The aim of this study is to review the published literature on isolated STIC to determine outcomes of these ients and present a summary of management strategies. METHODS. A systematic English-language literature search was conducted in PubMed, MEDLINE-Ovid, Scopus, EBSCO host, Cochrane Library of articles published from February 2006 to April 2015. Study inclusion criteria for review were the following: risk-reducing salpingo-oophorectomy (RRSO), BRCA mutation carriers, non-BRCA mutation carriers, and benign surgical indication. Exclusion criteria were as follows: the presence of synchronous gynecological cancers, concurrent non-gynecological malignancies, the presence of ovarian intraepithelial lesions, and articles that did not include any clinical information and were restricted to pathology information only. RESULTS. A total of 78 patients with isolated STIC were included in our analysis. The median age for all patients was 53.7 years (range; 37-83). Surgical indication was RRSO in 67 patients with BRCA mutations or high-risk personal or family history. In the other 11 patients, an incidental STIC was detected after surgery for non-cancerous indications. Eleven (16.4%) patients received chemotherapy after the diagnosis of STIC. The follow-up time ranged from 2 to 150 months. Three (4.5%) patients with BRCA mutations were diagnosed with primary peritoneal carcinoma (PPC) during the follow-up at 43, 48 and 72 months after RRSO. CONCLUSIONS. The rate of primary peritoneal carcinoma in patients with BRCA mutations and isolated STIC is 4.5%. The role of adjuvant therapy remains elusive and routine surveillance with tumor markers
Song, Jae-Won; Lee, Ju-Hong; Choi, Joon-Hyuk; Chun, Seok-Ju
Generally, pathological diagnosis using an electron microscope is time-consuming and likely to result in a subjective judgment, because pathologists perform manual screening of tissue slides at high magnifications. Recently, the advent of digital pathology technology has provided the basis for convenient screening and quantitative analysis by digitizing tissue slides through a computer system. However, a screening process with high magnification still takes quite a long time. To solve these problems, recently the use of computer-aided design techniques for performing pathologic diagnosis has been increasing in digital pathology. For pathological diagnosis, we need different diagnostic methods for different regions with different characteristics. Therefore, in order to effectively diagnose different lesions and types of diseases, a quantitative method for extracting specific features is required in computerized pathologic diagnosis. This study is about an automated differential diagnosis system to differentiate between benign serous cystadenoma and possibly-malignant mucinous cystadenoma. In order to diagnose cystic tumors, the first step is identifying a cystic region and inspecting its epithelial cells. First, we identify the lumen boundary of a cyst using the Direction Cumulative Map considering 8-ways. Then, the Epithelial Nuclei Identification algorithm is used to discern epithelial nuclei. After that, three morphological features for the differential diagnosis of mucinous and serous cystadenomas are extracted. To demonstrate the superiority of the proposed features, the experiments compared performance of the classifiers learned by using the proposed morphological features and the classical morphological features based on nuclei. The classifiers in the simulations are as follows; Bayesian Classifier, k-Nearest Neighbors, Support Vector Machine, and Artificial Neural Network. The results show that all classifiers using the proposed features have the best
Bjørnholt, Sarah Marie; Kjaer, Susanne Krüger; Nielsen, Thor Schütt Svane; Jensen, Allan
Do fertility drugs increase the risk for borderline ovarian tumours, overall and according to histological subtype? The use of any fertility drug did not increase the overall risk for borderline ovarian tumours, but an increased risk for serous borderline ovarian tumours was observed after the use of progesterone. Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs and risk for borderline ovarian tumours, and the results are inconsistent. A retrospective case-cohort study was designed with data from a cohort of 96 545 Danish women with fertility problems referred to all Danish fertility clinics in the period 1963-2006. All women were followed for first occurrence of a borderline ovarian tumour from the initial date of infertility evaluation until a date of migration, date of death or 31 December 2006, whichever occurred first. The median length of follow-up was 11.3 years. Included in the analyses were 142 women with borderline ovarian tumours (cases) and 1328 randomly selected sub-cohort members identified in the cohort during the follow-up through 2006. Cases were identified by linkage to the Danish Cancer Register and the Danish Register of Pathology by use of personal identification numbers. To obtain information on use of fertility drugs, hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register. We used case-cohort techniques to calculate rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for borderline ovarian tumours, overall and according to histological subtype, associated with the use of any fertility drug or five specific groups of fertility drugs: clomiphene citrate, gonadotrophins (human menopausal gonadotrophins and follicle
Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific
Ogłodek, Ewa; Araszkiewicz, Aleksander
For many years, the borderline personality disorders have mainly been researched in terms of psychoanalytical theories, such as theories on relations with the object. Nowadays, there are three kinds of concepts that are distinguishable. The first ones are those which are group models, serving attempts to made characteristic sets of qualities, represented by individuals suffering from the borderline personality disorders, more precise. The remaining concepts are models of conflict and deficit, which explain complicated mechanisms of interactions of social, psychological and biological factors, and therefore, contribute to better understanding of the genesis of the symptoms of this disorder. Upon the basis of the attempts made so far in the field of describing the borderline personality disorders, one may indicate certain criteria, representative for the entire group of individuals with this diagnosis, regardless of the assumptions applicable to the genesis of the disorder and its symptoms, even though the population of the infirm suffering from the borderline personality disorders is not internally homogenous. The interest of psychologists, attempting to describe the borderline personality disorders, is focused upon certain sets of qualities, presented as the examples of descriptive models. Among the researchers, working on the issues of the borderline personality disorders in this manner, there are: Gunderson, Kernberg, Kohut, Winnicot, Guntrip, Fairbaim, Adler and Buie.
Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi
In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder.
Cheon, Dong-Joo; Tong, Yunguang; Sim, Myung-Shin; Dering, Judy; Berel, Dror; Cui, Xiaojiang; Lester, Jenny; Beach, Jessica A.; Tighiouart, Mourad; Walts, Ann E.; Karlan, Beth Y.; Orsulic, Sandra
Purpose To elucidate molecular pathways contributing to metastatic cancer progression and poor clinical outcome in serous ovarian cancer. Experimental Design Poor survival signatures from three different serous ovarian cancer datasets were compared and a common set of genes was identified. The predictive value of this gene signature was validated in independent datasets. The expression of the signature genes was evaluated in primary, metastatic, and/or recurrent cancers using qPCR and in situ hybridization. Alterations in gene expression by TGFβ1 and functional consequences of loss of COL11A1 were evaluated using pharmacologic and knockdown approaches, respectively. Results We identified and validated a 10-gene signature (AEBP1, COL11A1, COL5A1, COL6A2, LOX, POSTN, SNAI2, THBS2, TIMP3, VCAN) that is associated with poor overall survival in patients with high-grade serous ovarian cancer. The signature genes encode extracellular matrix proteins involved in collagen remodeling. Expression of the signature genes is regulated by TGFβ1 signaling and is enriched in metastases in comparison to primary ovarian tumors. We demonstrate that levels of COL11A1, one of the signature genes, continuously increase during ovarian cancer disease progression, with the highest expression in recurrent metastases. Knockdown of COL11A1 decreases in vitro cell migration and invasion and tumor progression in mice. Conclusion Our findings suggest that collagen-remodeling genes regulated by TGFβ1 signaling promote metastasis and contribute to poor overall survival in patients with serous ovarian cancer. Our 10-gene signature has both predictive value and biological relevance and thus may be useful as a therapeutic target. PMID:24218511
The symptoms of, and possible treatments for 21 borderline and psychotic adolescents who had suffered from borderline psychoses in childhood were examined from a developmental point of view. It was concluded that therapeutic possibilities exist. Some childhood symptoms could be used directly in treatment, while others disappeared with general…
Unger, Ulrike; Denkert, Carsten; Braicu, Ioana; Sehouli, Jalid; Dietel, Manfred; Loibl, Sibylle; Darb-Esfahani, Silvia
HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer. In this study, we investigated HER3 on protein and mRNA expression in histologically defined subtypes of ovarian cancer looking for an influence on patient's survival. Altogether, we examined HER3 in ovarian high-grade serous (HGSC, n = 320), low-grade serous (LGSC, n = 55), endometrioid (EC, n = 33), and clear cell (CCC, n = 48) carcinomas using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR (qRT-PCR). Univariate and multivariate analyses were performed to explore the association between HER3 and overall survival (OS) as well as progression-free survival (PFS). In HGSC, high HER3 mRNA expression was a favorable prognostic factor for PFS (P = 0.008) and OS (P = 0.052), while for high HER3 protein expression, a trend towards better survival was seen (OS P = 0.064; PFS P = 0.099). A subgroup of HGSC with negative HER3 staining and negative HER3 mRNA levels showed most unfavorable OS and PFS (P = 0.002 and P = 0.004, respectively). Using the multivariate Cox regression model, HER3 was predictive for prolonged PFS (HR, 0.48; 95% CI, 0.26-0.88; P = 0.018). All in all, we cannot confirm the reported negative prognostic impact of HER3 expression in high-grade serous ovarian carcinoma and moreover find a rather positive prognostic implication of HER3 in this major ovarian cancer histological subtype.
Muallem, Mustafa Zelal; Parashkevova, Asya; Almuheimid, Jumana; Richter, Rolf; Diab, Yasser; Braicu, Elena Ioana; Sehouli, Jalid
The purpose of the study was to examine the preoperative CA-125 values as a predictive factor for postoperative outcome in primary serous ovarian cancer (POC) for complete tumor resection (CTR) and evaluate the preoperative CA-125 levels with other vital clinical dynamics such as ascites, lymph node involvement, diffuse peritoneal carcinomatosis, grading and staging. A cohort of 277 POC-patients aged 18-75 years, who had undergone primary cytoreductive surgery at the Department of Gynecology & Oncological Surgery, Charité, Campus Virchow Klinikum (CVK) between 2000 und 2009 was analyzed in correlation with the preoperative CA-125 values. The median preoperative CA-125 value in high-grade serous POC patients was 636 U/ml (204- 2312 U/ml) compared to 284 U/ml (148.5-1,378 U/ml) in low-grade serous POC patients (p=0.016). For the survival analyses both the cut-off values 252 and 475 U/ml, with highest sum from sensitivity (79.1% and 65.9%, respectively) and specificity (41.9% and 55.1%, respectively), were used to compare the relationship between preoperative CA-125 levels and (CTR), progression-free (PFS) and overall survival (OS). There was no significant difference between PFS and OS in three different groups of patients (preoperative CA-125 levels <252 U/ml, CA 125 levels between 252-475 U/ml and >475 U/ml). Preoperative CA-125 is a poor, but statistically significant predictive factor for CTR after PCS. Preoperative CA-125 can predict neither the progression-free nor overall survival for POC patients. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
The author outlines his concept of reflective function or mentalization, which is defined as the capacity to think about mental states in oneself and in others. He presents evidence to suggest that the capacity for reflective awareness in a child's caregiver increases the likelihood of the child's secure attachment, which in turn facilitates the development of mentalization in the child. He proposes that a secure attachment relationship offers the child a chance to explore the mind of the caregiver, and in this way to learn about minds; he formulates this model of the birth of the psychological self as a variation on the Cartesian cogito: "My caregiver thinks of me as thinking and therefore I exist as a thinker." This model is then applied to provide insight into some personality-disordered individuals who were victims of childhood abuse. The author proposes (1) that individuals who experience early trauma may defensively inhibit their capacity to mentalize to avoid having to think about their caregiver's wish to harm them; and (2) that some characteristics of severe borderline personality disorder may be rooted in developmental pathology associated with this inhibition. He offers evidence for and some qualifications of this model, and argues that the therapeutic effect of psychoanalysis depends on its capacity to activate patients' ability to evolve an awareness of mental states and thus find meaning in their own and other people's behavior.
Baker, L; Silk, K R; Westen, D; Nigg, J T; Lohr, N E
Malevolent object relations as well as splitting have long been considered by psychodynamic theorists as central features of borderline personality disorder. We tested the hypotheses that borderlines would a) perceive their parents more negatively than both nonborderline major depressive patients and nonpatient normal controls, and b) split their representations of their parents into opposites more than the comparison subjects. Borderlines (N = 31), who were identified by the Diagnostic Interview for Borderlines, Research Diagnostic Criteria major depressives (N = 15), and nonpatient controls (N = 14) were asked to rate each parent on the Adjective Check List (ACL; Gough and Heilbrun, 1983). Seven ACL scales were studied: Favorable, Unfavorable, Critical Parent, Nurturing Parent, Nurturance, Aggression, and Dominance. Correlations were performed between scores for mother and father on the various scales for each of the three cohorts. Analysis of variance and one-way t-tests with Bonferroni correction were used to test group differences. Borderlines rated their parents, especially their fathers, not only as more unfavorable on negative scales than depressives or normals, but as less favorable on positive scales than the comparison groups. Analysis of covariance revealed that a significant portion of the variance in father scores, but not in mother scores, was related to age of respondent and history of sexual abuse. While borderlines did not appear to split their parents into one good and one bad parent, they did show significantly less correlation between parents on the Favorable scale when compared with either depressives or normal subjects. The results imply that borderlines have a greater tendency to view the world in negative, malevolent ways than to split their object representations.
Howitt, Brooke E; Hanamornroongruang, Suchanan; Lin, Douglas I; Conner, James E; Schulte, Stephanie; Horowitz, Neil; Crum, Christopher P; Meserve, Emily E
Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.
Lee, James A; Zarnegar, Rasa; Shen, Wen T; Kebebew, Electron; Clark, Orlo H; Duh, Quan-Yang
To assess the risk of pheochromocytoma in patients with borderline-elevated urine or plasma metanephrine levels. Retrospective review. University tertiary care center. Forty-two consecutive patients with adrenal incidentalomas (defined as adrenal tumors identified during routine imaging for another condition) who were treated at the UCSF (University of California, San Francisco) Medical Center between January 1, 1995, and July 31, 2005. Patients with genetic syndromes were excluded. Laparoscopic adrenalectomy for adrenal incidentaloma based on size criteria and preoperative hormonal test results. Urine or plasma metanephrine and catecholamine levels, tumor size, and presence of pheochromocytoma. Of 42 patients, 14 (33%) had a pheochromocytoma (11 of whom had clear-cut elevations in urine or plasma metanephrine levels defined as greater than 2 times the upper limit of normal) and 28 did not. Ten of the 42 patients (24%) had borderline elevations in urine or plasma metanephrine levels (defined as 1-2 times the upper limit of normal), 3 of whom had a pheochromocytoma (30%). Of patients with borderline elevations, mean +/- SD tumor size was 5.4 +/- 3.1 and 4.8 +/- 1.9 cm for patients with and without pheochromocytoma, respectively (P = .37). In these 10 patients, no clinical factors (age, sex, hypertension, presence of symptoms, number of antihypertensive medications, preoperative hemodynamics, or size of tumor on computed tomographic scan) allowed differentiation between those with and without pheochromocytoma. Thirty percent of patients with adrenal incidentaloma and borderline-elevated urine or plasma metanephrine levels had a pheochromocytoma. Clinical factors cannot distinguish between those with and without pheochromocytoma. In this group of patients, we advocate either routine alpha-blockade preoperatively or further diagnostic tests to better characterize the tumor.
De Donato, Marta; Petrillo, Marco; Martinelli, Enrica; Filippetti, Flavia; Zannoni, Gian Franco; Scambia, Giovanni; Gallo, Daniela
Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of collagen and elastin in the extracellular matrix, thus controlling the tensile strength of tissues. Along with this primary function, there are evidences supporting a role for LOX in many critical biological functions, including gene expression regulation, cell growth, adhesion and migration. Accordingly, recent studies have supported a pivotal role for LOX in cancer progression and metastasis. The current study aimed at investigating the prognostic significance and the functional role of intracellular LOX in ovarian cancer. To this end, we analyzed LOX expression by immunohistochemistry in archived tumor material from advanced high grade serous ovarian cancer (HGSOC) patients (n=70) and correlated data with clinicopathological parameters and with response to chemotherapy. In vitro experiments were also used to investigate the functional consequences of LOX expression on behavioral aspects of HGSOC cells. Our results showed that nuclear LOX expression is associated with unfavorable outcome in advanced HGSOC, being an independent prognostic factor for disease recurrence. Besides, high nuclear levels were seen to be associated with resistance to first-line chemotherapy. Through gene expression modulation experiments in HGSOC cell lines, we demonstrate that LOX positively regulates cell proliferation, migration and anchorage-independent growth. Collectively, our data suggest that LOX functions as a tumor promoter in HGSOC and positively regulates several aspects of the metastatic cascade. Copyright © 2017 Elsevier Inc. All rights reserved.
Norouzpour, Amir; Abrishami, Majid
Central serous chorioretinopathy (CSC) is characterized by a localized accumulation of subretinal fluid and an idiopathic focal leakage from choroidal vessels. The exact pathogenesis of CSC, however, still remains obscure. In this paper, we hypothesized that CSC may result from a response of choroidal vessels to an acute increase in the environmental light intensity leading to a focal leakage from the choroidal vessels. High levels of glucocorticoids, in our proposed model, may cause persistence rather than initiation of the focal leakage, probably by suppressing the synthesis of collagen and extracellular matrix components and inhibiting fibroblastic activity. PMID:26949657
Andión-Fernández, M; Dorado-Fernández, T; Juárez-Casado, M A; Santamarina-Pernas, R
A 41-year-old woman with a bilateral loss of visual acuity and a history of IgA nephropathy. The ophthalmic examination revealed bilateral neurosensory detachments that resolved completely after four months of peritoneal dialysis. Bilateral serous retinal detachments are a rare manifestation of IgA nephropathy, in which the etiology is probably multifactorial and their resolution depends on the underlying disease. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Conrad, Rupert; Weber, Nina Friederike; Lehnert, Matthias; Holz, Frank Gerhard; Liedtke, Reinhard; Eter, Nicole
The authors studied 31 consecutive patients newly diagnosed with central serous chorioretinopathy (CSC) as compared with 31 age- and gender-matched control subjects, assessing emotional distress (ED), nine psychopathological symptoms, critical life events, and alexithymia. Results showed no difference in the number of critical life events; however CSC patients showed elevated ED and elevated scores on seven psychopathological symptoms, including hostility. Controlling for ED, CSC patients showed elevated alexithymia sum scores. Alexithymia was correlated with hostility. Our findings point to personality-based difficulties in emotional regulation associated with hostility in CSC.
Wilson, Andrew J.; Fadare, Oluwole; Beeghly-Fadiel, Alicia; Son, Deok-Soo; Liu, Qi; Zhao, Shilin; Saskowski, Jeanette; Uddin, Md. Jashim; Daniel, Cristina; Crews, Brenda; Lehmann, Brian D.; Pietenpol, Jennifer A.; Crispens, Marta A.; Marnett, Lawrence J.; Khabele, Dineo
Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors. PMID:25972361
Wilson, Andrew J; Fadare, Oluwole; Beeghly-Fadiel, Alicia; Son, Deok-Soo; Liu, Qi; Zhao, Shilin; Saskowski, Jeanette; Uddin, Md Jashim; Daniel, Cristina; Crews, Brenda; Lehmann, Brian D; Pietenpol, Jennifer A; Crispens, Marta A; Marnett, Lawrence J; Khabele, Dineo
Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors.
Bourgeois, Danielle L; Kabarowski, Karl A; Porubsky, Veronica L; Kreeger, Pamela K
The factors driving the onset and progression of ovarian cancer are not well understood. Recent reports have identified cell lines that are representative of the genomic pattern of high-grade serous ovarian cancer (HGSOC), in which greater than 90 % of tumors have a mutation in TP53. However, many of these representative cell lines have not been widely used so it is unclear if these cell lines capture the variability that is characteristic of the disease. We investigated six TP53-mutant HGSOC cell lines (Caov3, Caov4, OV90, OVCA432, OVCAR3, and OVCAR4) for migration, MMP2 expression, proliferation, and VEGF secretion, behaviors that play critical roles in tumor progression. In addition to comparing baseline variation between the cell lines, we determined how these behaviors changed in response to four growth factors implicated in ovarian cancer progression: HB-EGF, NRG1β, IGF1, and HGF. Baseline levels of each behavior varied across the cell lines and this variation was comparable to that seen in tumors. All four growth factors impacted cell proliferation or VEGF secretion, and HB-EGF, NRG1β, and HGF impacted wound closure or MMP2 expression in at least two cell lines. Growth factor-induced responses demonstrated substantial heterogeneity, with cell lines sensitive to all four growth factors, a subset of the growth factors, or none of the growth factors, depending on the response of interest. Principal component analysis demonstrated that the data clustered together based on cell line rather than growth factor identity, suggesting that response is dependent on intrinsic qualities of the tumor cell rather than the growth factor. Significant variation was seen among the cell lines, consistent with the heterogeneity of HGSOC.
Abushahin, Nisreen; Zhang, Tingguo; Chiang, Sarah; Zhang, Xiangsheng; Hatch, Kenneth; Zheng, Wenxin
Serous endometrial intraepithelial carcinoma (serous EIC) arising in adenomyosis is rare. It may be underrecognized because of its deceiving morphology when embedded in the foci of adenomyosis. Although there is no connection to peritoneal cavity, some cases may be associated with extrauterine disease. It is currently unknown what the etiology for such a disease is. More studies are in need to elucidate the pathogenesis of such a grave malady. We report a series of 5 cases of serous EIC, which may arise in adenomyosis. The 5 cases are in 5 different patients or whom on histopathological examination of their hysterectomy specimens, the finding of adenomyosis involved with serous intraepithelial neoplasia was identified. The finding of interest was the presence of multifoci of adenomyosis; some of those foci were involved in serous EIC. In addition to EIC, lesions of endometrial glandular dysplasia were present in the foci of adenomyosis. To rule out the possibility of endometrial serous carcinoma (ESC) invading into the areas of the adenomyosis, all of the 5 uteri were extensively examined. Among the 5 uteri, the eutopic endometirum showed 1 invasive ESC, 2 serous EIC, and 2 benign resting endometrium without any cancer or precancerous lesions. In 1 uterus with ESC, we did not see any direct spatial connection between the invasive component of ESC and the areas of EIC in the foci of adenomyosis. In 2 uteri with serous EIC within the endometrial cavity, there was a distance of at least 0.5 cm between the lesions within the endometrial cavity and the serous EIC in adenomyosis. The remaining 2 uteri showed no evidence of endometrial malignancy in the endometrial cavity, whereas serous EIC was present only in areas of adenomyosis. Clinicopathologic data including characterized immunohistochemical stainings and p53 gene sequence analysis are presented and clinical significance is discussed.
Sun, Yan; Guo, Fei; Bagnoli, Marina; Xue, Feng-Xia; Sun, Bao-Cun; Shmulevich, Ilya; Mezzanzanica, Delia; Chen, Ke-Xin; Sood, Anil K.; Yang, Da; Zhang, Wei
Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This “paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer. PMID:25556616
Gentile, Julie P.; Correll, Terry L.
The high prevalence of comorbid bipolar and borderline personality disorders and some diagnostic criteria similar to both conditions present both diagnostic and therapeutic challenges. This article delineates certain symptoms which, by careful history taking, may be attributed more closely to one of these two disorders. Making the correct primary diagnosis along with comorbid psychiatric conditions and choosing the appropriate type of psychotherapy and pharmacotherapy are critical steps to a patient's recovery. In this article, we will use a case example to illustrate some of the challenges the psychiatrist may face in diagnosing and treating borderline personality disorder. In addition, we will explore treatment strategies, including various types of therapy modalities and medication classes, which may prove effective in stabilizing or reducing a broad range of symptomotology associated with borderline personality disorder. PMID:20508805
Blutner, Reinhard; Pothos, Emmanuel M; Bruza, Peter
The term "vagueness" describes a property of natural concepts, which normally have fuzzy boundaries, admit borderline cases, and are susceptible to Zeno's sorites paradox. We will discuss the psychology of vagueness, especially experiments investigating the judgment of borderline cases and contradictions. In the theoretical part, we will propose a probabilistic model that describes the quantitative characteristics of the experimental finding and extends Alxatib's and Pelletier's () theoretical analysis. The model is based on a Hopfield network for predicting truth values. Powerful as this classical perspective is, we show that it falls short of providing an adequate coverage of the relevant empirical results. In the final part, we will argue that a substantial modification of the analysis put forward by Alxatib and Pelletier and its probabilistic pendant is needed. The proposed modification replaces the standard notion of probabilities by quantum probabilities. The crucial phenomenon of borderline contradictions can be explained then as a quantum interference phenomenon.
Alvarez, Rosa Maria; Vazquez-Vicente, Daniel
Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420
Paik, Daniel Y.; Janzen, Deanna M.; Schafenacker, Amanda M.; Velasco, Victor S.; Shung, May S.; Cheng, Donghui; Huang, Jiaoti; Witte, Owen N.; Memarzadeh, Sanaz
The reproductive role of the fallopian tube is to transport the sperm and egg. The tube is positioned to act as a bridge between the ovary where the egg is released and the uterus where implantation occurs. Throughout reproductive years the fallopian tube epithelium undergoes repetitive damage and regeneration. Although a reservoir of adult epithelial stem cells must exist to replenish damaged cells, they remain unidentified. Here we report isolation of a subset of basally located human fallopian tube epithelia (FTE) that lack markers of ciliated (β-tubulin; TUBB4) or secretory (PAX8) differentiated cells. These undifferentiated cells expressed cell surface antigens: epithelial cell adhesion molecule (EPCAM), CD44, and integrin alpha-6 (ITGA6). This fallopian tube epithelial subpopulation was five-fold enriched for cells capable of clonal growth and self renewal suggesting that they contain the fallopian tube epithelial stem-like cells (FTESC). A two-fold enrichment of the FTESC was found in the distal compared to the proximal end of the tube. The distal fimbriated end of the fallopian tube is a well characterized locus for initiation of serous carcinomas. An expansion of the cells expressing markers of FTESC was detected in tubal intraepithelial carcinomas (TIC) and in fallopian tubes from patients with invasive serous cancer. These findings suggest that FTESC may play a role in the initiation of serous tumors. Characterization of these stem-like cells will provide new insight into how the fallopian tube epithelia regenerate, respond to injury and may initiate cancer. PMID:22911892
Morency, Elizabeth; Leitao, Mario M; Soslow, Robert A
Many adnexal high-grade serous carcinomas (HGSCs) may derive from microscopic precursors in the fallopian tube. By studying a series of low-stage ovarian carcinomas, we anticipated that HGSCs would be distributed in a pattern suggesting secondary involvement, helping to indirectly validate the fallopian tube origin theory, and that most ovarian carcinomas other than serous carcinomas would demonstrate features consistent with derivation from precursors located in or transplanted to the ovary. Seventy-six patients with low-stage (FIGO I/II) sporadic ovarian carcinoma who underwent primary surgical management at Memorial Sloan Kettering Cancer Center from 1980 to 2000 were included in the study. Histologic type was assigned using Gilks' criteria. Similar to the approach taken when distinguishing primary and metastatic mucinous or endometrioid carcinoma involving ovary, cases interpreted as showing a "primary" pattern of ovarian involvement had ≥3 of the following features: unilateral tumor, size >12 cm, no surface involvement, no multinodularity, and no destructive stromal invasion. All other cases were considered to show a "metastatic" pattern of ovarian involvement. Cases were evaluated for p53 and WT-1 expression, using standard techniques on a tissue microarray. TP53 gene sequencing was also performed. Cases comprised HGSC (n=22), endometrioid carcinoma (n=30), clear cell carcinoma (n=13), and mucinous carcinoma (n=11). HGSCs displayed substantially more "metastatic features" than the non-HGSC group and a mean overall size that was smaller (8.85 vs. 14.1 cm). Statistically significant differences were found for bilaterality (63% vs. 7.3%), P=0.0001; multinodularity (55% vs. 7.3%), P=0.0001; tumor size, P=0.003; and surface involvement (50% vs. 13%), P=0.002. Five of 22 (23%) of HGSCs showed a "primary pattern" of ovarian involvement. There were no significant differences between these cases and "metastatic pattern" HGSCs when comparing morphology
di Giacomo, Ester; Aspesi, Flora; Fotiadou, Maria; Arntz, Arnoud; Aguglia, Eugenio; Barone, Lavinia; Bellino, Silvio; Carpiniello, Bernardo; Colmegna, Fabrizia; Lazzari, Marina; Lorettu, Liliana; Pinna, Federica; Sicaro, Aldo; Signorelli, Maria Salvina; Clerici, Massimo
Borderline Personality (BPD) and Bipolar (BP) disorders stimulate an academic debate between their distinction and the inclusion of Borderline in the Bipolar spectrum. Opponents to this inclusion attribute the important differences and possible diagnostic incomprehension to overlapping symptoms. We tested 248 Borderline and 113 Bipolar patients, consecutively admitted to the Psychiatric Unit, through DSM-IV Axis I and II Disorders (SCID-I/II), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS) and Borderline Personality Disorder Severity Index-IV (BPDSI-IV). All the tests statistically discriminated the disorders (p < 0.0001). Overlapping symptoms resulted significantly different (impulsivity = 5.32 in BPD vs 1.55 in BP, p < 0.0001; emotional instability = 7.11 in BPD vs 0.55 in BP, p < 0.0001) and the range of their scores gives the opportunity for an even more precise discrimination. Distinctive traits (e.g. irritability or sexual arousal) are also discussed in order to try to qualify the core of these disorders to a higher degree. Comorbidity proves to be extremely small (3.6%). However, Borderline patients with manic features offer a privileged point of view for a deeper analysis. This allows for the possibility of a more precise examination of the nature and load of each symptom. Borderline Personality and Bipolar Disorders can be distinguished with high precision using common and time-sparing tests. The importance of discriminating these clinical features may benefit from this evidence.
Costanzo, Eliana; Cohen, Salomon Yves; Miere, Alexandra; Querques, Giuseppe; Capuano, Vittorio; Semoun, Oudy; El Ameen, Ala'a; Oubraham, Hassiba; Souied, Eric H.
Purpose. To analyze optical coherence tomography angiography (OCTA) findings in eyes with central serous chorioretinopathy (CSC) and to compare them with those obtained with multimodal imaging. Methods. A series of consecutive patients diagnosed with CSC, underwent OCTA and multimodal imaging, including spectral domain OCT, fluorescein, and indocyanine green angiography. OCTA images were performed at three main depth intervals: automatically segmented outer retina, manually adjusted outer retina, and automatically segmented choriocapillaris. Results. Thirty-three eyes of 32 consecutive patients were analyzed. OCTA showed 3 main anomalies at the choriocapillaris: the presence of dark areas (19/33 eyes) which were frequently associated with serous retinal detachment, presence of dark spots (7/33 eyes) which were frequently associated with retinal pigment epithelium detachment, and presence of abnormal vessels (12/33 eyes) which were frequently, but not systematically, associated with choroidal neovascularization, as confirmed by multimodal imaging. Conclusions. OCTA revealed dark areas and dark spots, which were commonly observed. An abnormal choroidal pattern was also observed in one-third of cases, even when multimodal imaging did not evidence any choroidal neovascularization. Abnormal choroidal vessels should be interpreted with caution, and we could assume that this pathological choroidal vascular pattern observed in many CSC cases could be distinct from CNV. PMID:26634150
Gajdzik-Gajdecka, Urszula; Dorecka, Mariola; Nita, Ewa; Michalska, Anna; Miniewicz-Kurkowska, Joanna; Romaniuk, Wanda
Summary Background Central serous chorioretinopathy (CSC) is a condition that originates from alterations of the choroidal circulation. The aim of this paper was to evaluate the use of indocyanine green angiography (ICGA) in patients with chronic CSC. Material/Methods The analysis included 17 patients (34 eyes) with chronic CSC in at least 1 eye. The eye examination included: distance and near visual acuity, biomicroscopy, applanation tonometry, fundus examination, colored and red-free fundus photography, evaluation of autofluorescence, optical coherence tomography, and fluorescein and indocyanine green angiography. Results In 34 eyes (100%) involved in the ICGA study the results revealed zones of transient increased choroidal vessels permeability. In 18 eyes (52.9%) choroidal changes were accompanied by a focal serous pigment epithelial detachment. In 4 eyes (11.8%) of 3 patients’ the ICGA examination confirmed the presence of occult choroidal neovascularization (CNV). In the patient with bilateral diffuse retinal pigment epitheliopathy, CNV was present in 1 eye, in the patient with unilateral chronic CSC it was also present in 1 eye, and in the third patient with bilateral chronic CSC it was detected in both eyes. Conclusions ICGA is a very useful examination that enables ophthalmologists to visualize choroidal changes due to chronic CSC, as well as to diagnose occult CNV in chronic CSC. PMID:22293877
Gajdzik-Gajdecka, Urszula; Dorecka, Mariola; Nita, Ewa; Michalska, Anna; Miniewicz-Kurowska, Joanna; Romaniuk, Wanda
Central serous chorioretinopathy (CSC) is a condition that originates from alterations of the choroidal circulation. The aim of this paper was to evaluate the use of indocyanine green angiography (ICGA) in patients with chronic CSC. The analysis included 17 patients (34 eyes) with chronic CSC in at least 1 eye. The eye examination included: distance and near visual acuity, biomicroscopy, applanation tonometry, fundus examination, colored and red-free fundus photography, evaluation of autofluorescence, optical coherence tomography, and fluorescein and indocyanine green angiography. In 34 eyes (100%) involved in the ICGA study the results revealed zones of transient increased choroidal vessels permeability. In 18 eyes (52.9%) choroidal changes were accompanied by a focal serous pigment epithelial detachment. In 4 eyes (11.8%) of 3 patients' the ICGA examination confirmed the presence of occult choroidal neovascularization (CNV). In the patient with bilateral diffuse retinal pigment epitheliopathy, CNV was present in 1 eye, in the patient with unilateral chronic CSC it was also present in 1 eye, and in the third patient with bilateral chronic CSC it was detected in both eyes. ICGA is a very useful examination that enables ophthalmologists to visualize choroidal changes due to chronic CSC, as well as to diagnose occult CNV in chronic CSC.
Rahman, W; Horgan, N; Hungerford, J
We describe a rare case of bilateral circumscribed choroidal haemangioma in an otherwise healthy male, which mimicked chronic central serous chorioretinopathy (CSCR). A 52-year-old Asian man presented with a one-year history of visual decline in his left eye. The vision in the right eye had been reduced for 15 years. Visual acuity was 6/60 in the right eye and 6/18 in the left eye. Fundus examination of the right eye revealed an area of discoloration with overlying retinal pigment epithelial changes in the macula and evidence of prior surrounding argon laser photocoagulation. The left macula showed a raised choroidal lesion with overlying retinal pigment epithelial changes and associated subretinal fluid. This appearance illustrates how chronic retinal pigment epithelial alterations associated with longstanding subretinal fluid exudation from circumscribed choroidal haemangiomas may mimick the appearance of chronic central serous chorioretinopathy. B-scan ultrasonography, fluorescein angiography, indocyanine green angiography and optical coherence tomography helped to establish the diagnosis. The active lesion in the left eye was treated with verteporfin photodynamic therapy with improvement in vision.
Galindo, José; Gabrielli, Mauricio; Guerra, Juan Francisco; Cassina, Juan Carlos; Garrido, Marcelo; Jarufe, Nicolás; Borghero, Yerko; Madrid, Jorge; Zoroquiain, Pablo; Roa, Juan Carlos; Martínez, Jorge
Pancreatic cancer remains as one of the most aggressive human neoplasms, with overall poor survival rates. Radical surgery of the primary lesion is the best option for treatment. Borderline resectable pancreatic tumors (BRPT), defined as partial involvement of peripancreatic vasculature, may benefit from neoadjuvant therapy. We report on the first two BRPT cases treated with neoadjuvant chemoradiation at our institution. Preoperative CT and MRI demonstrated pancreatic tumors encasing the porto-mesenteric confluence suggestive of BRPT. Patients received neoadjuvant chemotherapy (gemcitabine/cisplatin), followed by radiochemotherapy. After treatment, follow-up images demonstrated tumor downsize, allowing for the tumors to be considered then as resectable. They underwent partial pancreatoduodenectomies (Whipple procedure). In case 1, histopathology revealed a complete, margin-free resection, whereas in case 2 there was a complete pathological response, with no evidence of residual tumor. According to the literature, our initial experience using neoadjuvant chemoradiotherapy on BRPT allowed us to downsize the tumor and, subsequently, to perform a curative surgery.
Zhou, Jun; Gong, Guanghui; Tan, Hong; Dai, Furong; Zhu, Xin; Chen, Yile; Wang, Junpu; Liu, Ying; Chen, Puxiang; Wu, Xiaoying; Wen, Jifang
MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR-30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR-30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a-5p suppressed the
Khaki, Fariba; Javanbakht, Javad; Sharifzad, Samieh; Gharagozlou, Mohammad Javad; Khadivar, Farshid; Manesh, Javad Yaghoobi Yeganeh; Hosseini, Seyed Hojjat; Anissian, Ali; Touni, Seyed Rashid; Gilvari, Alireza; Abdi, Fatemeh Soghra
Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma.
Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424
Crum, Christopher P; McKeon, Frank D; Xian, Wa
In recent years, the distal oviduct has emerged as a critical organ in the pathogenesis of pelvic ("ovarian") serous cancer. Studies have uncovered early serous tubal intraepithelial carcinomas in approximately 8% of asymptomatic women with germline BRCA1 or BRCA2 mutations, linked serous tubal intraepithelial carcinomas to one half of serous cancers irrespective of genetic risk, and described a precursor lesion in the distal tube with early alterations in p53 function (the p53 signature). This work has established a linear serous carcinogenic sequence in a single focus within the fimbria. In addition, a more broadly distributed array of gene alterations has been discovered in the oviduct, manifested as secretory (or stem) cell outgrowths that are increased in frequency as a function of older age and serous cancer status. These "surrogate precursors" expand the existing model beyond the fimbria, implying that the molecular events leading to serous cancer are distributed over space and time. The potential promise of these discoveries is "targeted prevention" by discovering of multiple pathways integral to carcinogenesis and successfully preventing malignancy by interrupting one or a few of these pathways.
Ussakli, Cigdem; Usubutun, Alp; Dincer, Nazmiye; Dolgun, Anil; Bülbül, Diilek; Isikdogan, Zuhal; Haberal, Nihan; Ozen, Ozlem; Tezel, Gaye Guler
We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.
Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H.; Zhang, Bai; McDermott, Jason E.; Zhou, Jian-Ying; Petyuk, Vladislav A.; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A.; Clauss, Therese R.; Choi, Caitlin; Monroe, Matthew E.; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J.; Yu, Kun-Hsing; Tabb, David L.; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S.; Hiltke, Tara; Rivers, Robert C.; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P.; Levine, Douglas A.; Smith, Richard D.; Chan, Daniel W.; Rodland, Karin D.
Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes, while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies. Components of
Ludolph, P S; Westen, D; Misle, B; Jackson, A; Wixom, J; Wiss, F C
Adult criteria for borderline personality disorder distinguished a group of 27 inpatient adolescent girls from 23 nonborderline inpatient female comparison subjects. The two groups were compared on retrospectively assessed variables measuring psychological, familial, and constitutional factors. Variables most likely to predict borderline personality disorder included history of disrupted attachments, maternal neglect, maternal rejection, grossly inappropriate parental behavior, number of mother and father surrogates, physical abuse, and sexual abuse. Families of borderline adolescents were chronically disrupted, particularly during the patients' early childhoods. The traumatic childhood experiences of the borderline adolescents were similar to those of adults with borderline personality disorder in recent studies.
Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin
Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells varies with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (P < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers.
Ricciardelli, Carmela; Lokman, Noor A; Pyragius, Carmen E; Ween, Miranda P; Macpherson, Anne M; Ruszkiewicz, Andrew; Hoffmann, Peter; Oehler, Martin K
This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03-2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12-3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.
Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin
Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells vary with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (p < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers.
Gunderson, J G; Berkowitz, C; Ruiz-Sancho, A
The development of the psychoeducational form of treatment described in this article has been prompted by changes in our understanding of borderline psychopathology and changes in the health care system in which these patients are treated. After reviewing these background changes, the authors describe the treatment itself, its form, its purpose, and the preliminary suggestions of its effectiveness.
Waldo, Michael; Harman, Marsha J.
Briefly describes Borderline Personality Disorder (BPD) and explains Relationship Enhancement (RE) marital and family therapy. Provides rationale for understanding BPD as manifestation of lack of differentiation in intimate relationships, followed by explanation of how RE fosters differentiation between partners. Includes case study. (Author/NB)
Sansone, Lori A.
Obesity is a significant health problem in the United States. Therefore, it is extremely important to understand potential clinical associations with obesity, including personality pathology. From studies of personality disorders in other types of eating pathology, it appears that restrictive personality disorders (e.g., obsessive-compulsive disorder) are associated with restrictive eating pathology (e.g., anorexia nervosa, restricting type) whereas impulsive personality disorders (e.g., borderline personality disorder) are associated with impulsive eating pathology (e.g., anorexia nervosa, binge-eating/purging type; bulimia nervosa, binge eating disorder). Because binge eating disorder is oftentimes associated with an obese status, it seems likely that borderline personality disorder may also be associated with obesity. At the present time, there appear to be nine accessible studies in this area, comprising 639 obese individuals. While rates of borderline personality disorder in these studies vary from 2.2 to 94.1 percent, 10 of 19 measures detected this disorder at rates of 25 percent or higher, and the average of all percentages is 26.9 percent. Findings appear to support the association between impulsive personality pathology and impulsive eating pathology, and underscore that a significant minority of obese individuals may suffer from borderline personality disorder. PMID:23696958
Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa
The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health…
Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa
The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health…
Carey, Mark S.; Agarwal, Roshan; Gilks, Blake; Swenerton, Kenneth; Kalloger, Steve; Santos, Jennifer; Ju, Zhenlin; Lu, Yiling; Zhang, Fan; Coombes, Kevin; Miller, Dianne; Huntsman, David; Mills, Gordon B.; Hennessy, Bryan T
Purpose: Using Reverse Phase Protein Array (RPPA) we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage high-grade serous ovarian cancer. Experimental Design: Tumor samples were obtained from forty-five patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by RPPA. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization, and Cox regression to test for the association between protein expression and PFS. A significance level of p ≤ 0.05 was used. Results: The mean age at diagnosis was 56.8 years. EGFR, YKL-40 and several TGFβ pathway proteins (c-Jun N-terminal kinase JNK, JNK phosphorylated at residues 183 and 185, PAI-1, Smad3, TAZ) showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, EGFR (p < 0.02), JNK (p < 0.01), and Smad3 (p < 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGFβ pathway proteins was unlikely due to false discovery (p < 0.007, Bonferroni-adjusted). Conclusion: TGFβ pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. PMID:20460476
Esposito, Nicole Nicosia; Mohan, Deepak; Brufsky, Adam; Lin, Yan; Kapali, Malathy; Dabbs, David J
Phyllodes tumors (PTs) of the breast are biphasic neoplasms composed of epithelium and a spindle-cell stroma. Currently, PTs are classified as benign, borderline, or malignant based on histopathologic features. However, histologic classification does not always predict outcome. Objective.-To determine the prognostic value of a variety of clinicopathologic features and immunoreactivities in PTs. Sixteen benign, 8 borderline, and 6 malignant PTs with follow-up were examined for reactivity across a panel of immunohistochemical stains, including c-Kit, endothelin 1, p16, p21, p53, and Ki-67. Clinicopathologic features, including stromal cellularity, mitotic rate, and margin status, were also assessed. Tumor variables were compared among tumor subgroups and between tumors that did and did not recur. Of the 30 PTs, 4 recurred (1 benign, 2 borderline, 1 malignant). One patient with a malignant tumor died of metastatic disease 34 months after initial diagnosis. The overall positive rate of c-Kit immunoreactivity was 13% in benign, 63% in borderline, and 67% in malignant PTs. Endothelin 1 epithelial cytoplasmic staining was seen in 100% of benign, 50% of borderline, and 17% of malignant PTs. Additionally, p16, p21, p53, and Ki-67 were differentially expressed among benign, borderline, and malignant tumors. Positive surgical resection margins was the only variable that significantly predicted recurrent disease (P = .02). Stromal c-Kit positivity and epithelial endothelin 1 negativity are more often associated with malignant PTs; however, only positive margin status is significantly associated with tumor behavior.
Cheng, Zhongping; Yang, Weihong; Guo, Jing; Luo, Ning; Chen, Li; Xie, Yan; Qu, Xiaoyan; Hu, Liping; Dai, Hong; Zuo, Xiaoming
The present report aimed to study genetic alterations underlying extraovarian peritoneal serous papillary carcinoma (EPSPC), which have not previously been systematically investigated. A case of EPSPC was identified, and its genetic alterations were assessed by combining comparative genomic hybridization and whole-exome sequencing technologies to investigate the genomic landscape, including copy number variations and mutations in EPSPC. It was found that a large number of germline mutations were present, which may have predisposed the patient to the occurrence of this disease. Copy number gains were found in a range of chromosomes, including 4q, 5q, 8q, 10q, 15q, 16p, 18q, 20p, 20q and Xq. Large-scale copy number loss occurred in chromosomes 2p, 13q, 16q, 17p and 17q. Through use of whole-exome sequencing, germline mutations were widely found that were associated with cancer development, including mutations in the BRCA1, DNA repair associated (BRCA1), BRCA2, tumor protein 53, erb-b2 receptor tyrosine kinase 2, matrix metalloproteinases and ADAM metallopeptidase domain-containing genes. In addition, 165 somatic mutations, including 52 missense mutations and 7 short insertions or deletions, were also identified. In summary, the EPSPC was undergoing profound genomic rearrangement and somatic mutation, which may have led to its initiation and development, and the present study discussed the genetic basis of this highly malignant cancer. PMID:27698805
Hao, Dapeng; Li, Jingjing; Jia, Shanshan; Meng, Yuan; Wang, Li; Zhang, Chao; Di, Li-Jun
The relative importance of fallopian tube (FT) compared to ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs. A collection of transcriptome data of 80 FTs, 89 OSEs and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and OSE-like tumors. A molecular signature was developed for identifying tissue origin of SOC and then was used to re-evaluate the prognostic genes and therapeutic biomarkers of SOC of different tissue origins. IHC staining of tissue array and functional experiments on a panel of ovarian cancer cell lines were used to further validate the key findings. The expression patterns of tissue specific genes, prognostic genes and molecular markers all support a dualistic tissue origin of SOC, from either FT or OSE. A molecular signature was established to identify the tissue identity of SOCs. Surprisingly, the signature showed a strong association with overall survival [OSE-like versus FT-like, HR = 4.16, 95%CI, 2.67-6.48, p<10-9]. The phamacogenomic approach revealed AXL to be a therapeutic target of the aggressive OSE-derived SOC. SOC has two subtypes originated from either FT or OSE, which show different clinical and pathological features. Copyright ©2017, American Association for Cancer Research.
Chen, Xiaoxiang; Zhang, Jing; Zhang, Zhihong; Li, Hongxia; Cheng, Wenjun; Liu, Jinsong
Although epithelial ovarian cancer cells are eliminated by debulking surgery and chemotherapy during initial treatment, it is believed that only a subset of cancer cells, that is, cancer stem cells, may be an important source of tumor recurrence and drug resistance. This review highlights our current understanding of high-grade serous carcinoma, ovarian cancer stem cells, common methods for enrichment of ovarian cancer stem cells, mechanisms involved in drug resistance, and potential strategies for overcoming drug resistance, with associated potential controversies and pitfalls. We also review the potential relationship between epithelial-to-mesenchymal transition and cancer stem cells and how we can induce cancer cells to differentiate into benign stromal fibroblasts in response to certain chemotherapy drugs.
Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.; Nagano, Osamu; Saya, Hideyuki; Lage, Kasper; Donahoe, Patricia K.; Pépin, David
CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be
Gruessner, Christine; Gruessner, Angelika; Glaser, Katherine; AbuShahin, Nisreen; Laughren, Cynthia; Zheng, Wenxin; Chambers, Setsuko K
Introduction: BRCA mutations increase the risk for development of high-grade pelvic serous carcinomas. Tissue biomarkers distinguishing women at high-risk (HR) for ovarian cancer from those at low-risk (LR) may provide insights into tumor initiation pathways. Methods: A prospective study of 47 HR women (40% BRCA carriers) undergoing risk-reducing salpingo-oophorectomy and 48 LR controls undergoing salpingo-oophorectomy was performed. Ovarian/tubal tissues were harvested. Immunohistochemical analysis of candidate proteins CSF-1, CSF-1R, ErbB4 is presented, with scores separately analyzed in epithelium and stroma, in ampulla, fimbria, ovary, and ovarian endosalpingiosis (ES). Comparison was performed between HR and LR groups. Results: Elevated levels of CSF-1 (p=0.005) or ErbB4 (p=0.005) in the ovarian epithelium, or ErbB4 (p=0.005) in the ovarian stroma, were significantly associated with both the HR status and carrying a BRCA mutation, as was nuclear ErbB4 staining. Ovarian ES, an entity which likely derives from the tubal mucosal epithelium, was also associated with HR (p=0.038) and BRCA mutation status (p=0.011). Among the BRCA carriers only, markers also found association when present in the tube as well as in ovarian ES (p < 0.05). ROCs were generated including in the regression model both CSF-1 and ErbB4 expression levels. A model including CSF-1 in ovarian epithelium, ErbB4 in ovarian stroma, and younger age achieves AUC=0.87 (73% sensitivity, 93% specificity) of detection of the HR status. In BRCA carriers, CSF-1 in ovarian epithelium alone achieves AUC=0.85. Conclusions: Our data suggest that elevated levels of CSF-1/ErbB4 in the adnexae correlate with HR/BRCA carrier status. CSF-1/CSF-1R signaling is active in ovarian cancer progression; our data suggests a role in its initiation. ErbB4, in particular nuclear ErbB4, may have a role in tumor initiation as well. Ovarian ES, an entity which may represent a latent precursor to low-grade pelvic serous
Yavelsky, Victoria; Rohkin, Sarit; Shaco-Levy, Ruthy; Tzikinovsky, Alina; Amir, Tamar; Kohn, Hila; Delgado, Berta; Rabinovich, Alex; Piura, Benjamin; Chan, Gerald; Kalantarov, Gavreel; Trakht, Ilya; Lobel, Leslie
Background We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. Methods The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. Results By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. Conclusion The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases
Yavelsky, Victoria; Rohkin, Sarit; Shaco-Levy, Ruthy; Tzikinovsky, Alina; Amir, Tamar; Kohn, Hila; Delgado, Berta; Rabinovich, Alex; Piura, Benjamin; Chan, Gerald; Kalantarov, Gavreel; Trakht, Ilya; Lobel, Leslie
We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that
Vieira, Luisa; Silva, Nuno Aguiar; Medeiros, Marco Dutra; Flores, Rita; Maduro, Vitor
Acute lymphoblastic leukemia is a malignant hematopoietic neoplasia, which is rare in adults. Although ocular fundus alterations may be commonly observed in the course of the disease, such alterations are rarely the presenting signs of the disease. Here we describe the case of a patient with painless and progressive loss of visual acuity (right eye, 2/10; left eye, 3/10) developing over two weeks, accompanied by fever and cervical lymphadenopathy. Fundus examination showed bilateral macular serous detachment, which was confirmed by optical coherence tomography. Fluorescein angiography revealed hyperfluorescent pinpoints in the posterior poles. The limits of the macular detachment were revealed in the late phase of the angiogram. The results of blood count analysis triggered a thorough, systematic patient examination. The diagnosis of acute lymphoblastic leukemia B (CD10+) was established, and intensive systemic chemotherapy was immediately initiated. One year after the diagnosis, the patient remains in complete remission without any ophthalmologic alterations.
Nicholson, Benjamin; Noble, Jason; Forooghian, Farzin; Meyerle, Catherine
Recent technological advances have led to an improved understanding of central serous chorioretinopathy (CSC): new pathophysiological insights, new imaging techniques for diagnosis and management, and new treatments. The primary role of the choroid has become more widely accepted with widespread use of indocyanine green angiography. Optical coherence tomography (OCT), and particularly enhanced depth imaging OCT, demonstrate a thickened and engorged choroid. Adaptive optics, fundus autofluorescence, multifocal electroretinography, microperimetry, and contrast sensitivity testing reveal that patients with even a mild course suffer previously undetected anatomic and functional loss. While focal laser and photodynamic therapy are the current standard of care for persistent subretinal fluid in CSC, they are not appropriate in all cases, and the optimal timing of intervention remains unclear. PMID:23410821
Seeber, Laura M S; Zweemer, Ronald P; Marchionni, Luigi; Massuger, Leon F A G; Smit, Vincent T H B M; van Baal, W Marchien; Verheijen, René H M; van Diest, Paul J
Promoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC.
von Rückmann, Andrea; Fitzke, Frederick W; Fan, Joseph; Halfyard, Anthony; Bird, Alan C
To report abnormalities of fundus autofluorescence associated with acute and chronic central serous retinopathy (CSR). A prospective cohort study of patients with CSR was undertaken in which the intensity and spatial distribution of fundus autofluorescence were documented. Fundus autofluorescence was recorded using a confocal laser scanning ophthalmoscope (cLSO) and the images compared with the fundus appearance and fluorescein angiograms in 69 eyes of 63 subjects with either acute or chronic CSR. Areas of increased and decreased autofluorescence were compared with ophthalmoscopic and fluorescein angiography abnormalities. Thirty patients with focal leakage on angiography and serous retinal detachment or pigment epithelial detachment were designated as having acute CSR. Thirty-three patients with diffuse leakage on fluorescein angiography, but without manifest detachment were classified as having chronic CSR. The mean age was 39 years (range 29-56 years) 14 were female and 49 male. Acute CSR of more than 4 months duration showed a mild diffuse increase in autofluorescence that corresponded with the detached area. The leaking point on the angiogram corresponded to a focal area of intense autofluorescence. In chronic CSR the autofluorescence was very irregular, there being regions with greater and less than the background levels of fluorescence. In acute CSR, increased autofluorescence may occur at the site of leakage and in the area of retinal detachment probably indicating an increased metabolic activity of the retinal pigment epithelium (RPE). Decreased or absent autofluorescence in long-standing lesions may indicate reduced metabolic activity of the RPE due to photoreceptor cell loss. Documenting photoreceptor cell loss with autofluorescence imaging may be useful in identifying patients who would not benefit from laser photocoagulation.
Conway, Christopher C; Hipwell, Alison E; Stepp, Stephanie D
Borderline personality disorder (PD) historically is construed as an unremitting condition with poor prognosis. The present study takes a new approach to examining stability and change in borderline PD by explaining symptom expression in terms of an unchanging foundation-termed borderline proneness-on one hand, and transitory influences on the other. We monitored borderline PD symptoms annually in a large sample of high-risk adolescent girls (N = 2,450) from ages 14 to 20. Trait-state-occasion modeling revealed that just over half (52-57%) of borderline PD symptom variation was attributable to fixed borderline proneness, whereas the remainder was subject to change across yearly measurement occasions. This degree of stability was no larger than the corresponding estimate for depression, a condition known for its variable course. Our results indicate that, contrary to its reputation, borderline pathology is not set in stone, and it fluctuates in response to situational influences.
Clarke, Blaise; Virtanen, Carl; Plotkin, Anna; Rosen, Barry; Bernardini, Marcus Q.; Brown, Theodore J.; Murphy, K. Joan
Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC), which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade. We compared genome-wide gene expression profiles from a discovery cohort of ten patients diagnosed with stages III-IV HGSOC with high-volume ascites and nine patients with low-volume ascites. An upregulation of immune response genes was detected in tumors from patients presenting with low-volume ascites relative to those with high-volume ascites. Immunohistochemical studies performed on tissue microarrays confirmed higher expression of proteins encoded by immune response genes and increased tumorinfiltrating cells in tumors associated with low-volume ascites. Comparison of 149 advanced-stage HGSOC cases with differential ascites volume at time of primary surgery indicated low-volume ascites correlated with better surgical outcome and longer overall survival. These findings suggest that advanced stage HGSOC presenting with low-volume ascites reflects a unique subgroup of HGSOC, which is associated with upregulation of immune related genes, more abundant tumor infiltrating cells and better clinical outcomes. PMID:24982872
Villalba-Pinto, Luis; Hernández-Ortega, M. Ángeles; de los Mozos, F. Javier Lavid; Pascual-Camps, Isabel; Dolz-Marco, Rosa; Arevalo, J. Fernando; Gallego-Pinazo, Roberto
Introduction Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID:25120474
Pomykala, Matthew; Rubin, Phillip; Rubin, Jeffrey S
To describe a rare case of recurring central serous chorioretinopathy associated with retinitis pigmentosa successfully treated with oral acetazolamide. A 17-year-old male with retinitis pigmentosa who developed four separate episodes of central serous chorioretinopathy over a 12-month period. After the patient's fourth recurrence, he was treated with daily oral acetazolamide, which resulted in resolution of submacular fluid. He has had no subsequent recurrences while being maintained on alternating and then biweekly doses of oral acetazolamide. Recurrent central serous chorioretinopathy associated with retinitis pigmentosa is a rare occurrence. The presented case demonstrates that oral acetazolamide successfully treated and may have delayed recurrent episodes of central serous chorioretinopathy in the patient with retinitis pigmentosa.
Iannetti, Ludovico; Spinucci, Giovanni; Pesci, Francesca Romana; Vicinanza, Roberto; Stigliano, Antonio; Pivetti-Pezzi, Paola
To report a case of Cushing syndrome due to adrenocortical adenoma revealed by central serous chorioretinopathy. A 45-year-old man presented with blurred vision and metamorphopsia in the left eye. He reported few episodes of high blood pressure in the last 3 months. Visual acuity was 20/40 in the left eye. Fundus oculi examination revealed central serous chorioretinopathy in the left eye. Grade 1 hypertension was found. Increased serum and urinary levels of cortisol and reduced serum levels of ACTH were observed. Diagnosis of Cushing syndrome was made. Computed tomography scan revealed a right adrenal mass that was surgically removed; histologic examination showed an adrenocortical adenoma. Three months after surgical treatment, visual acuity improved to 20/20 and central serous chorioretinopathy completely resolved. Central serous chorioretinopathy may be the presenting symptom of Cushing syndrome in a patient with adrenocortical adenoma.
Ladhani, Noor Niyar N; Chari, Radha S; Dunn, Michael S; Jones, Griffith; Shah, Prakesh; Barrett, Jon F R
The primary objective of this guideline was to develop consensus statements to guide clinical practice and recommendations for obstetric management of a pregnancy at borderline viability, currently defined as prior to 25+6 weeks. Clinicians involved in the obstetric management of women whose fetus is at the borderline of viability. Women presenting for possible birth at borderline viability. This document presents a summary of the literature and a general consensus on the management of pregnancies at borderline viability, including maternal transfer and consultation, administration of antenatal corticosteroids and magnesium sulfate, fetal heart rate monitoring, and considerations in mode of delivery. Medline, EMBASE, and Cochrane databases were searched using the following keywords: extreme prematurity, borderline viability, preterm, pregnancy, antenatal corticosteroids, mode of delivery. The results were then studied, and relevant articles were reviewed. The references of the reviewed studies were also searched, as were documents citing pertinent studies. The evidence was then presented at a consensus meeting, and statements were developed. The content and recommendations were developed by the consensus group from the fields of Maternal-Fetal Medicine, Neonatology, Perinatal Nursing, Patient Advocacy, and Ethics. The quality of evidence was rated using criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (reference 1). The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations, Assessment, Development, and Evaluation methodology framework. The interpretation of strong and weak recommendations is described later. The Summary of Findings is available upon request. A multidisciplinary approach should be used in counselling women and families at borderline
van den Doel, E M
The diagnosis of a "serous apoplexy," customary in the first half of the 19th century, was based on the lack of knowledge regarding the normal presence of the cerebrospinal fluid. Balzac's descriptions of three cases of serous apoplexy draw our attention to the fact that the discovery of the cerebrospinal fluid by François Magendie was not assimilated into clinical medicine until the second half of the 19th century.
Villella, J A; Cohen, S; Smith, D H; Hibshoosh, H; Hershman, D
Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of endometrial cancer with features similar to high-grade ovarian cancer. Patients tend to be elderly, thin, have a high grade tumor with extensive extrauterine disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistochemistry in <25% of ovarian cancers and 20-30% of breast cancers, and <10% of endometrial cancer. There are prognostic and therapeutic implications associated with the overexpression of this transmembrane protein. Herceptin, a humanized murine monoclonal antibody directed against the extracellular domain of the HER-2/neu protein, is being used to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and 19 patients had specimens available for evaluation. We performed immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of 19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five patients had advanced disease at diagnosis. Two of these patients were subsequently treated with Herceptin; one with complete response and one with stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be beneficial for a select group of patients with UPSC. We are continuing to evaluate samples for HER-2/neu over expression by fluorescence in situ hybridization (FISH).
Stringer-Reasor, Erica M.; Baker, Gabrielle M.; Skor, Maxwell N.; Kocherginsky, Masha; Lengyel, Ernst; Fleming, Gini F.; Conzen, Suzanne D.
Objectives To test the hypothesis that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer (HGS-OvCa) and that treatment with a GR antagonist will improve sensitivity to chemotherapy. Methods GR expression was assessed in OvCa cell lines by qRT-PCR and Western blot analysis and in xenografts and primary human tumors using immunohistochemistry (IHC). We also examined the effect of GR activation versus inhibition on chemotherapy-induced cytotoxicity in OvCa cell lines and in a xenograft model. Results With the exception of IGROV-1 cells, all OvCa cell lines tested had detectable GR expression by Western blot and qRT-PCR analysis. Twenty-five out of the 27 human primary HGS-OvCas examined expressed GR by IHC. No cell line expressed detectable progesterone receptor (PR) or androgen receptor (AR) by Western blot analysis. In vitro assays showed that in GR-positive HeyA8 and SKOV3 cells, dexamethasone (100 nM) treatment upregulated the pro-survival genes SGK1 and MKP1/DUSP1 and inhibited carboplatin/gemcitabine-induced cell death. Concurrent treatment with two GR antagonists, either mifepristone (100 nM) or CORT125134 (100 nM), partially reversed these effects. There was no anti-apoptotic effect of dexamethasone on chemotherapy-induced cell death in IGROV-1 cells, which did not have detectable GR protein. Mifepristone treatment alone was not cytotoxic in any cell line. HeyA8 OvCa xenograft studies demonstrated that adding mifepristone to carboplatin/gemcitabine increased tumor shrinkage by 48% compared to carboplatin/gemcitabine treatment alone (P=0.0004). Conclusions These results suggest that GR antagonism sensitizes GR+ OvCa to chemotherapy-induced cell death through inhibition of GR-mediated cell survival pathways. PMID:26115975
Buza, Natalia; English, Diana P; Santin, Alessandro D; Hui, Pei
HER2 overexpression and/or amplification have been reported in endometrial serous carcinoma, suggesting that HER2 may be a promising therapeutic target. However, there is considerable variation in the reported rates of HER2 overexpression and amplification, likely--at least in part--resulting from variability in the testing methods, interpretation, and scoring criteria used. Unlike in breast and gastric cancer, currently there are no established guidelines for HER2 testing in endometrial carcinoma. A total of 108 endometrial carcinoma cases--85 pure serous carcinomas and 23 mixed endometrial carcinomas with serous component--were identified over a 4-year period. All H&E and HER2 immunohistochemical slides were reviewed and HER2 FISH results (available on 52 cases) were retrieved from pathology reports. HER2 immunohistochemical scores were assigned according to the FDA criteria and the current breast ASCO/CAP scoring criteria. Clinical information was retrieved from the patients' medical records. Thirty-eight cases (35%) showed HER2 overexpression and/or gene amplification, 20 of which (53%) had significant heterogeneity of protein expression by immunohistochemistry. Lack of apical membrane staining resulting in a lateral/basolateral staining pattern was observed in the majority of HER2-positive tumors. Five of the HER2-positive cases (13%) demonstrated discrepant immunohistochemical scores when using the FDA versus ASCO/CAP scoring system. The overall concordance rate between HER2 immunohistochemistry and FISH was 75% (39/52) when using the FDA criteria, compared with 81% (42/52) by the ASCO/CAP scoring system. In conclusion, in this largest comprehensive study, 35% of endometrial serous carcinoma harbors HER2 protein overexpression and/or gene amplification, over half of which demonstrate significant heterogeneity of protein expression. The current breast ASCO/CAP scoring criteria provide the highest concordance between immunohistochemistry and FISH. Assessment of
Schatz, Patrik; Aldayel, Ahmed; Taskintuna, Ibrahim; Abdelkader, Ehab; Mura, Marco
Proliferative diabetic retinopathy is a major cause of visual impairment in working-age adults worldwide. Panretinal photocoagulation is a cornerstone in its management; however, it may include a range of side effects and complications, one of these being serous retinal detachment. To the best of our knowledge, this is the first report of the use of intravitreal injection of bevacizumab for serous retinal detachment after panretinal photocoagulation. A 24-year-old Saudi man with poorly controlled type 1 diabetes presented with bilateral progressive proliferative retinopathy in spite of several sessions of panretinal photocoagulation. After one additional such session, he developed bilateral serous retinal detachment and vision loss, which was managed with a single bilateral intravitreal bevacizumab injection. The serous retinal detachment subsided with partial recovery of vision. Serous retinal detachment after panretinal photocoagulation for proliferative diabetic retinopathy is a rare complication nowadays. In this case, it seems that excessive photocoagulation exceeded the energy-absorbing capacity of the retinal pigment epithelium, leading to a disruption of the blood-retinal barrier. A single injection of bilateral intravitreal bevacizumab was sufficient to control the serous retinal detachment. This effect may have been due to a reduction of vascular leakage resulting from the mechanism of action of this drug. No complications were noted from the injection. Caution should be exerted when attempting bilateral panretinal photocoagulation.
Lis, Stefanie; Bohus, Martin
Studies on natural long-term course of borderline personality disorder (BPD) as well as on treatment outcome suggest that social integration remains seriously unsatisfactory in the majority of the subjects concerned. Identification of typical borderline problems in social interaction should facilitate both, treatment development and elucidation of the related neuropsychological mechanisms and underpinnings. This review focuses on the experimental investigation of three core domains of social interaction: social affiliation, cooperation and hostility. Data converge, that patients meeting criteria for BPD show a tendency to misinterpret neutral situations, feel socially rejected during normative inclusion conditions and reveal difficulties in repairing cooperation after experiencing disappointment. While from a clinical perspective, most attention has been focused on relationships of BPD patients with their significant others, the literature suggests that encounters with unknown individuals also indicate impairments in interaction behavior, and that such impairments can be linked to altered cerebral processing. Considering these findings psychosocial treatments should extend the programs and develop trainings in normative behavior.
De Oliveira, C; Rahioui, H; Smadja, M; Gorsane, M A; Louppe, F
The borderline personality disorder is a complex psychiatric disorder that represents a high number of patients in a psychiatric adult service. Even if some therapies have shown to be effective in the therapeutic care of the borderline personality disorder they only target certain symptoms (e.g. anxiety, sadness, self-mutilation). The aim of this paper is to introduce a therapeutic model little known in France: the mentalization based therapy (MBT) developed in 2004 by Bateman and Fonagy. This therapeutic model apprehends the borderline personality disorder in all its complexity and is based on two main concepts: Bowlby's attachment theory and the concept of mentalization. The MBT is based on the hypothesis that a deficit of mentalization leads to the development of borderline disorder. The capacity of mentalization, also known as reflexive function, is acquired in infancy through interpersonal relationships, in particular those of attachment, and is the ability to understand the mental state (emotions, needs, thoughts, etc.) of oneself and others which underlies explicit behaviour. This reflexive capacity is of a better quality when the person has a secure attachment style. Indeed, borderline patients have, mainly, a deficit of mentalization capacity associated with an insecure attachment style. Thus, the main objective of the Bateman and Fonagy approach is to develop and reinforce the mentalization capacity through a therapeutic relationship as a secure base, a group therapy and the concept of insight. Classically, MBT is structured over a period of 18 months divided into 3 distinct phases distributed in two therapeutic axes: group and individual therapy. The initial phase aims to engage the patient in the therapy by evaluating attachment style, mentalization's ability, interpersonal functioning; providing psychoeducation about borderline disorder and establishing a therapeutic contract. To evaluate attachment style, the authors strongly recommend the use of the
Biskin, Robert S.
Objectives: Borderline personality disorder (BPD) is frequently encountered in both adult and youth populations. There is a robust literature supporting psychotherapy for adults with BPD, but the literature supporting its use for BPD in youth is more limited. Methods: A literature review was conducted using the keywords “borderline personality disorders” and “adolescence.” Relevant articles were reviewed for inclusion. Results: Several specialized treatments have been studied with mixed results. Dialectical behaviour therapy has no randomized controlled trials in adolescents, emotion regulation training has not demonstrated superiority of treatment as usual, and cognitive analytic therapy has demonstrated more rapid recovery but little difference at follow-up. Mentalization-based treatment has one study supporting its use in self-harming adolescents. Pharmacotherapy has no evidence supporting its use in this population. Conclusions: Structured therapy may be the most important therapeutic component in this population. PMID:23970912
Helgeland, Margareth I; Torgersen, Svenn
Developmental antecedents of borderline personality disorders (BPDs) were examined in 25 DSM-IV-diagnosed subjects with BPD and 107 non-borderline control subjects on the basis of medical records and 28 years follow-up. Abuse, neglect, environmental instability, paternal psychopathology, and lower score on protective factors differentiated significantly between the groups. Environmental instability and lower score on protective factors such as artistic talents, superior school performance, above average intellectual skills, and talents in other areas were found to be independent predictors of BPD diagnosis. The results of this study suggest that both abuse and neglect, unpredictable and unstable early environment, as well as deficit in protective factors may substantially contribute to the development of BPD in persons constitutionally predisposed for the disorder. The results of the study also suggest that future research should address the impact of social and cultural context, as well as the absence of protective factors, on the development of the BPD.
Kröger, Christoph; Vonau, Melanie; Kliem, Sören; Kosfelder, Joachim
Borderline personality disorder (BPD) is a life-threatening mental disorder. To date, there is no German screening tool available. To examine the psychometric properties of a German version of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD). A heterogeneous outpatient sample (N=168) was used to examine discriminatory ability, diagnostic efficiency as well as indicators for internal consistency and convergent validity. The area under the curve was AUC=0.90 (CI 95%: 0.85
Psychotherapies specifically designed for borderline personality disorder (BPD) are the most effective form of treatment for this population, but these modalities are not easily accessible. Narrative review. Although research shows that such therapies are effective, the best-known methods are lengthy, expensive, and difficult for patients to access. This review recommends that interventions for patients with BPD should be briefer, less costly, and more accessible.
Vender, Simone; Callegari, Camilla; Poloni, Nicola
The borderline personality disorders are very frequent in modern society because of cultural and social reasons. The authors analyze the disturbed mental processes (impulsiveness and memory) because they represent risk factors for the treatment of diseases. On the base of experience of consultation-liaison psychiatry, the authors show some guidelines in the medical practice (primary care and general hospital) in order to overcome the troubles of the treatment.
Levallius, Johanna; Rydén, Göran; Norring, Claes
Patients with borderline personality disorder have a characteristic and extreme personality associated with psychopathology. The aim was to investigate personality change in relation to suicidality following treatment. 21 patients were assessed before and after psychotherapy on personality (NEO PI-R) and suicidality (SUAS). At follow-up, Neuroticism and Conscientiousness normalized along with six lower-order facets; Depression, Impulsiveness, Competence, Achievement Striving, Self-Discipline and Deliberation. Thirteen patients showed a positive personality development paralleled by a lesser degree of suicidality.
Paris, Joel; Chenard-Poirier, Marie-Pierre; Biskin, Robert
Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) have an overlap in both symptoms and risk factors, suggesting that they might reflect the same form of psychopathology, shaped by gender. However other lines of evidence point to the presence of partly unique, albeit overlapping, trait dimensions, specifically affective instability which differentiates BPD from ASPD. Our conclusion is that ASPD and BPD are separate disorders. Copyright © 2013 Elsevier Inc. All rights reserved.
Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine
The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.
Dewhurst, Catherine E; Mortele, Koenraad J
Cystic tumors of the pancreas are a subset of rare pancreatic tumors that vary from benign to malignant. Many have specific imaging findings that allow them to be differentiated from each other. This article (1) reviews the imaging features of the common cystic pancreatic lesions, including serous microcystic adenoma, mucinous cystic tumor, intraductal papillary mucinous tumor, and solid pseudopapillary tumor, and including the less common lesions such as cystic endocrine tumors, cystic metastases, cystic teratomas, and lymphangiomas; and (2) provides comprehensive algorithms on how to manage the individual lesions, with recommendations on when to reimage patients. Copyright © 2012 Elsevier Inc. All rights reserved.
SANTISTEBAN, DANIEL A.; MUIR, JOAN A.; MENA, MAITE P.; MITRANI, VICTORIA B.
With the growing acceptance of the borderline personality disorder diagnosis for adolescents has come a need for specialized treatments for this challenging population. Further, because of the prominence of the family system during early and later adolescence, family treatments are particularly needed. The purpose of this article is to present the integrative borderline adolescent family therapy (I-BAFT) model that emerged from a National Institute on Drug Abuse–funded (Stage 1) treatment development and enhancement effort. I-BAFT integrates (a) key interventions from the family treatment of adolescent drug abuse (D. A. Santisteban et al., 2003; J. Szapocznik & W. Kurtines, 1989), (b) skills training shown effective with adults with borderline personality disorder (M. Linehan, 1993a) and adapted for adolescents, and (c) individual treatment interventions that promote motivation for treatment and enhance the integration of the 3 treatment components. PMID:25663719
Tsai, Wen-Chiuan; Jin, Jong-Shiao; Yu, Jyh-Cherng; Sheu, Lai-Fa
The discrimination of borderline from malignant primary breast phyllodes (PT) tumor is still unclear. We studied 22 PT cases to investigate the immunohistochemical expression (staining of stromal CD10, SMA [smooth muscle actin], and vimentin) as well as the features of focal glandular atypia to determine whether these correlated with the histopathologic grading system. In our results, the stromal staining of CD10 was positive in 4 of 6 malignant and 2 of 5 borderline PT cases, but negative in all benign PT cases. Stromal actin and intraglandular vimentin-expressive tumor cells were found in 5 of 6 malignant PT cases but not in borderline and benign PT cases. There is a significant difference in the panel of stromal CD10, actin, and vimentin expression between borderline and malignant PT (p<0.05). Besides, the progression of malignant potential breast phyllodes tumor may cause glandular epithelium atypia with loss of polarity.
Hilvo, Mika; de Santiago, Ines; Gopalacharyulu, Peddinti; Schmitt, Wolfgang D.; Budczies, Jan; Kuhberg, Marc; Dietel, Manfred; Aittokallio, Tero; Markowetz, Florian; Denkert, Carsten; Sehouli, Jalid; Frezza, Christian
Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition (EMT) gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID:26685161
To investigate the efficacy of intravitreal bevacizumab injection in patients with acute central serous chorioretinopathy (CSCR). Between 6 weeks and 3 months, 13 eyes of 22 patients with acute CSCR received an intravitreal bevacizumab injection (2 mg/0.08 mL), 9 eyes had no medical treatment as a control. At baseline and follow-up visits patients had best corrected visual acuity (BCVA), intraocular pressure assessment, dilated fundus examination, and spectral optical coherence tomography imaging. Outcome measures were the resolution of neurosensory detachment, improvement in visual acuity, and symptoms. All patients showed prompt improvements of visual acuity and symptoms until the 3rd month and recovered from neurosensory detachment gradually following treatment in the study group. The vision of control subjects recovered later and the regression of serous retinal detachments were fairly slow. The mean BCVA improved from 0.39±0.16 at first visit (at baseline) to 0.73±0.17 at the 6th month in the study group; and, from 0.25±0.17 at first visit (at baseline) to 0.67±0.13 at the 6th month in the control group that was statistically significant (P=0.0001; P=0.0001, respectively). Mean retinal thickness for the study group was decreased from 414.38±102.79 at first visit (at baseline) to 256.46±84.77 at the 3rd month and 198.30±29.81 at the 6th month (P=0.0001, P=0.0001); and that for the control group was decreased from 510.33±80.59 at first visit (at baseline) to 336.33±127.83 at the 3rd month and 205.66±19.65 at the 6th month (P=0.004, P=0.0001, respectively). One of the patients in the control group revealed recurrence at the 6th month and the patient was given intravitreal injection of bevacizumab. Intravitreal bevacizumab injection for acute CSCR can lead to remarkable improvements of visual acuity within 3 months follow-up compared with controls. These results demonstrated that intravitreal bevacizumab injection may be a promising option for
Shah, Ronak H.; Scott, Sasinya N.; Brannon, A. Rose; Levine, Douglas A.; Lin, Oscar; Berger, Michael F.
BACKGROUND Mutation analysis for personalized treatment has become increasingly important in the management of different types of cancer. The advent of new DNA extraction protocols and sequencing platforms with reduced DNA input requirements might allow the use of cytology specimens for high-throughput mutation analysis. In this study, the authors evaluated the use of effusion fluid for next-generation sequencing-based, multigene mutation profiling. METHODS Four specimens from each of 5 patients who had at least stage III, high-grade serous ovarian carcinoma were selected: effusion fluid; frozen tumor; formalin-fixed, paraffin embedded tumor; and matched normal blood. Frozen tumors from each patient were previously characterized by The Cancer Genomic Atlas (TCGA). DNA was extracted from all specimens and was sequenced using a custom hybridization capture-based assay. Genomic alterations were compared among all specimens from each patient as well as with mutations reported in TCGA for the same tumors. RESULTS In total, 17 distinct somatic mutations were identified in the cohort. Ten of 17 mutations were reported in TCGA and were called in all 3 malignant specimens procured from the patients. Of the remaining 7 mutations, 2 were called in all 3 specimens, and the other 5 were sample-specific. Two mutations were detected only in the cytology specimens. Copy number profiles were concordant among the tumors analyzed. CONCLUSIONS Cytology specimens represent suitable material for high-throughput sequencing, because all mutations described by TCGA were independently identified in the effusion fluid. Differences in mutations detected in samples procured from the same patient may reflect tumor heterogeneity. PMID:25655233
Sharma, Sai Kiran; Sevak, Kuntal K; Monette, Sebastien; Carlin, Sean D; Knight, James C; Wuest, Frank R; Sala, Evis; Zeglis, Brian M; Lewis, Jason S
The elevation of cancer antigen 125 (CA125) levels in the serum of asymptomatic patients precedes the radiologic detection of high-grade serous ovarian cancer by at least 2 mo and the final clinical diagnosis by 5 mo. PET imaging of CA125 expression by ovarian cancer cells may enhance the evaluation of the extent of disease and provide a roadmap to surgery as well as detect recurrence and metastases. (89)Zr-labeled mAb-B43.13 was synthesized to target CA125 and evaluated via PET imaging and biodistribution studies in mice bearing OVCAR3 human ovarian adenocarcinoma xenografts. Ex vivo analysis of tumors and lymph nodes was performed via autoradiography, histopathology, and immunohistochemistry. PET imaging using (89)Zr-DFO-mAb-B43.13 (DFO is desferrioxamine) clearly delineated CA125-positive OVCAR3 xenografts as early as 24 h after the administration of the radioimmunoconjugate. Biodistribution studies revealed accretion of (89)Zr-DFO-mAb-B43.13 in the OVCAR3 tumors, ultimately reaching 22.3 ± 6.3 percentage injected dose per gram (%ID/g) at 72 h after injection. Most interestingly, activity concentrations greater than 50 %ID/g were observed in the ipsilateral lymph nodes of the xenograft-bearing mice. Histopathologic analysis of the immuno-PET-positive lymph nodes revealed the presence of grossly metastasized ovarian cancer cells within the lymphoid tissues. In control experiments, only low-level, non-specific uptake of (89)Zr-labeled isotype IgG was observed in OVCAR3 tumors; similarly, low-activity concentrations of (89)Zr-DFO-mAb-B43.13 accumulated in CA125-negative SKOV3 tumors. Immuno-PET with (89)Zr-labeled mAb-B43.13 is a potential strategy for the noninvasive delineation of extent of disease and may add value in treatment planning and treatment monitoring of high-grade serous ovarian cancer. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Wang, Jianjun; Liu, Qi; Zhou, Xiaodie; He, Yan; Guo, Qing; Shi, Qunli; Eriksson, Staffan; Zhou, Ji; He, Ellen; Skog, Sven
Cancer is a disease with abnormally proliferating cells and therefore proliferation rate is an important index for assessing tumour growth. Ki-67 is a commonly used proliferation marker considered to be an unfavourable prognostic marker in some tumors, while Thymidine kinase 1 (TK1) is an interesting proliferation marker because its levels are highly dependent on the growth stage of cells. To define the immunohistochemistry (IHC) expression of the TK1 in patients with ovarian serous adenocarcinoma and establish its potential role as a new biomarker for progressive disease, we analyzed the expression patterns of TK1 and Ki-67 in 109 patients with ovarian serous adenocarcinoma. TK1 and Ki-67 expression both showed a statistically significant correlation to MD Anderson Cancer Center (MDACC) grade, but not to age, tumour size, lymph node metastasis or pathological TNM (pTNM) stages. TK1 expression, MDACC grades, pathological stages and lymph node metastasis correlate to relapse incident rate and overall survival, but Ki-67 does not. Although TK1 expression, MDACC grade, pTNM stage and lymph node metastasis significantly correlate to relapse in the Cox univariate analysis, in the multivariate Cox analysis only TK1 expression and lymph node metastasis were independent prognostic factors. The overall survival also correlated significantly to TK1 expression, MDACC grade, pTNM stage and lymph node metastasis in the Cox univariate analysis. However, only the pTNM stage was found to be an independent prognostic factor for survival in the Cox multivariate analysis. Therefore, though TK1 expression was an independent prognostic factor for relapse, but not for survival, TK1 is a more informative expression than Ki-67 for LI, relapse and overall survival rates. Thus, when TK1 is combined with MDACC grading, pTNM staging and lymph node metastasis, IHC determination of TK1 expression may improve the overall prediction of prognosis in patients with ovarian cancer.
Belkacemi, Yazid Bousquet, Guilhem; Marsiglia, Hugo; Ray-Coquard, Isabelle; Magne, Nicolas; Malard, Yann; Lacroix, Magalie; Gutierrez, Cristina; Senkus, Elzbieta; Christie, David; Drumea, Karen; Lagneau, Edouard; Kadish, Sidney P.; Scandolaro, Luciano; Azria, David; Ozsahin, Mahmut
Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size = 3 cm and no tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. Conclusions: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.
Studies using indocyanine green angiography (ICGA) revealed that the main cause of central serous chorioretionopathy (CSC) stems from choroidal abnormalities such as choroidal vascular hyperpermeability. However, there are no methods to evaluate the choroid except for either the invasive ICGA or low-resolution ultrasonography. The recently developed enhanced depth imaging optical coherence tomography (EDI-OCT) technique can visualize the choroid appropriately and noninvasively using conventional OCT. EDI-OCT showed that both the affected and unaffected eyes in CSC patients have a thickened choroid; whereas the remarkably thickened choroid in Vogt-Koyanagi-Harada disease decreases immediately after corticosteroid treatment and the eyes with high myopia show a thinner choroid. We evaluated the choroidal thickness after treatment of CSC. The subfoveal choroidal thickness in typical CSC treated with laser photocoagulation showed no changes during the follow-up. On the other hand, the subfoveal choroid in chronic CSC treated with half-dose verteporfin photodynamic therapy (PDT) showed temporary thickening after 2 days but thinned back 1 month after treatment. Both the choroidal thickness and choroidal vascular hyperpermeability in ICGA decreased after PDT, but they did not change after laser photocoagulation. These findings suggest that PDT can affect the abnormal choroid directly and works through a different mechanism from conventional laser photocoagulation. It is important to evaluate the choroid using OCT in CSC and other macular diseases.
Lahousen, Theresa; Painold, Annamaria; Luxenberger, Wolfgang; Schienle, Anne; Kapfhammer, Hans-Peter; Ille, Rottraut
Central serous chorioretinopathy (CSC) has been associated with several psychological factors. But previous psychological data are limited and mainly restricted to male patients and small sample size. In this study we investigated psychosomatic complaints, personality factors, life events, and stress coping in acute and chronic recurrent CSC patients. Ninety-five patients (71 men, 24 women) with either acute or chronic CSC were evaluated regarding critical life events before diagnosis, psychosomatic complaints, personality traits and coping style. The characteristics of CSC patients were compared with a control group comprising 75 patients (46 men, 29 women) suffering from acute or chronic ophthalmic disorders other than CSC. Compared with patients of the control group, CSC patients reported more psychosomatic problems, unfavourable stress coping strategies and critical life events as well as elevated tension, aggression, strain, emotional instability and achievement orientation. Except for aggression the observed characteristics were more pronounced in acute than in chronic CSC patients. The appearance of CSC may be associated with an accumulation of stressful life events with an unfavourable coping style and distinctive personality factors. Acute CSC is related to more unfavourable stress coping and more physical complaints compared to its chronic course. Elevated aggression may imply one potential risk factor for CSC manifestation and also may have an adverse effect with its chronification.
Islam, Qamar Ul; Farooq, Muhammad Asad; Mehboob, Mohammad Asim
Objective: To determine the visual outcome in patients with acute Central serous chorioretinopathy (CSCR) and to analyze the association of clinical, angiographic and tomographic factors with final visual outcome in Pakistani population. Methods: This study was conducted at AFIO Rawalpindi and PNS Shifa Naval hospital Karachi from November 2011 to August 2016. Fifty five eyes of 53 patients with acute CSCR were included. All patients underwent a detailed ophthalmic examination including SD OCT imaging at baseline, One month and three month and FFA was performed at baseline. Primary outcome measures were measurement of initial and final BCVA and CFT. SPSS 13.0 was used for the analysis of data. Results: Mean age of study population was 36.66 ± 6.24 years. On OCT mean CFT at baseline was 467.49 ± 144.80 µm in affected eye, whereas mean CFT measurements at final follow up was 244.67 ± 32.99 µm (p <0.01). Presenting mean log MAR BCVA was 0.47 ± 0.25 and final mean log MAR BCVA was 0.18 ± 0.14 (p <0.01). Baseline BCVA showed statistically significant association with final BCVA (p=0.03). Conclusion: Presenting VA of 6/12 or better is associated with favorable visual outcome in patients with acute CSCR. PMID:28367162
Roelofsen, Thijs; Geels, Yvette P; Pijnenborg, Johanna M A; van Ham, Maaike A P C; Zomer, Saskia F; van Tilburg, Johanna M Wiersma; Snijders, Marc P M L; Siebers, Albert G; Bulten, Johan; Massuger, Leon F A G
The aim of this study was to determine the frequency of abnormal cervical cytology in preoperative cervical cytology of patients diagnosed with uterine papillary serous carcinoma (UPSC) and endometrioid endometrial carcinoma (EEC). In addition, associations between abnormal cervical cytology and clinicopathologic factors were evaluated. In this multicentre study, EEC patients diagnosed at two hospitals from 1999 to 2009 and UPSC patients diagnosed at five hospitals from 1992 to 2009, were included. Revision of the histologic slides was performed systematically and independently by 3 gynecopathologists. Cervical cytology within six months before histopathologic diagnosis of endometrial carcinoma was available for 267 EEC and 80 UPSC patients. Cervical cytology with atypical, malignant, or normal endometrial cells in postmenopausal women was considered as abnormal cytology, specific for endometrial pathology. Abnormal cervical cytology was found in 87.5% of UPSC patients, compared with 37.8% in EEC patients. In UPSC, abnormal cytology was associated with extrauterine spread of disease (P=0.043). In EEC, abnormal cytology was associated with cervical involvement (P=0.034). In both EEC and UPSC patients, abnormal cervical cytology was not associated with survival. In conclusion, abnormal cervical cytology was more frequently found in UPSC patients. It was associated with extrauterine disease in UPSC patients, and with cervical involvement in EEC patients. More prospective research should be performed to assess the true clinical value of preoperative cervical cytology in endometrial cancer patients.
de Leeuw, F a; Rijcken, F e m; Trum, J w; van der Noort, V; Tjon-Kon-Fat, R i; Bleeker, M c g; Kenter, G g
Summary Uterine serous carcinoma (USC) is an aggressive, histological subtype of endometrial cancer with a poor prognosis. This study evaluates the additional effect of staging surgery above total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH+BSO) on the use of adjuvant therapy and subsequent survival outcomes in clinical early-stage USC patients. This retrospective cohort study includes 75 women treated for clinical early-stage USC. In 33 (44%) clinical early-stage patients surgical staging was performed and 15 patients (45%) proved to have lymphatic or abdominal metastasis. Use of adjuvant therapy was similar in patients, both staged with no metastasis (n = 18) and patients who underwent TAH and BSO only (n = 42, p = 0.17). No significant survival difference was found between surgically staged and TAH+BSO patients. Surgical staging proved to be important to determine stage of disease and hence prognosis. Surgical staging did not lead to selective avoidance of adjuvant therapy in patients with no metastasis.
Singh, Rishi P; Sears, Jonathan E; Bedi, Rumneek; Schachat, Andrew P; Ehlers, Justis P; Kaiser, Peter K
AIM To examine eplerenone (Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy (CSCR). METHODS A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit, spectral domain optical coherence tomography (SD-OCT) imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy. RESULTS A total of 17 eyes of 13 patients treated with 25 and 50 mg of oral eplerenone per day were identified. Subretinal fluid (SRF) decreased over time following eplerenone therapy (P= 0.007 and P = 0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 µm at baseline to 15.3 µm at day 181+. SRF diameter decreased from an average of 2174.4 µm at baseline to 46.9 µm at day 181+. LogMAR visual acuity improved from 0.42 (Snellen equivalent: 20/53) at baseline to 0.29 (Snellen equivalent: 20/39) at day 181+ (P = 0.024). Central subfield thickness (CST) decreased from 339.5 µm at baseline to 270.3 µm at day 181+ (P = 0.029). CONCLUSION Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR. PMID:25938046
Moon, Hoseok; Lee, Dae Yeong; Nam, Dong Heun
AIM To evaluate the axial length (AXL) in unilateral idiopathic central serous chorioretinopathy (CSC). METHODS This retrospective case-control study was comprised of a consecutive case series of 35 patients with acute unilateral idiopathic CSC, and age- and sex-matched 50 control eyes. AXL of both eyes of unilateral CSC patients and the control eyes were investigated. AXL was measured by ultrasonic biometry, and the adjusted AXL was calculated for CSC eyes as measured AXL plus differences of foveal thickness between CSC and normal fellow eyes in millimeters. The main outcome measures were comparison of AXL between CSC, fellow and control eyes. RESULTS The mean age of 35 CSC patients was 45.5y, and 31 males were included. The adjusted AXL of CSC eyes was 23.52 mm, and the AXL of fellow eyes was 23.46 mm, and of control eyes 23.94 mm. The AXL of both CSC and fellow eyes were significantly shorter than control eyes (CSC vs control, P=0.044; fellow vs control, P=0.026). There was no statistically significant difference in AXL between CSC and fellow eyes. CONCLUSION In unilateral idiopathic CSC, the AXL of CSC and fellow eyes are shorter than that of control eyes. Short AXL may be related with choroidal circulation abnormality in CSC. PMID:27275428
Zonta, Yohan Ricci; Martinez, Marcelo; Camargo, Isabel Cristina C; Domeniconi, Raquel F; Lupi Júnior, Luiz Antonio; Pinheiro, Patricia Fernanda F; Reiter, Russel J; Martinez, Francisco Eduardo; Chuffa, Luiz Gustavo A
Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.
Obuchi, Toru; Shimooki, Osamu; Sasaki, Akira; Abe, Tadashi; Wakabayashi, Go
In February 2007, a 41-year-old Japanese male was admitted to our hospital with increasing upper abdominal pain. A contrast-enhanced computed tomography (CT) scan of the abdomen demonstrated a well-demarcated, hypodense cystic mass with a thickened wall in the mesocolon. The laboratory results were within normal limits, except for increased carcinoembryonic antigen, carbohydrate antigen 19-9, DUPAN-2 and SPAN-1. The patient was diagnosed as having a mesenteric malignant cyst, and during a laparotomy, a right hemicolectomy with mesenteric cystectomy was performed without rupture in March 2007. In the microscopic findings, there was a well-differentiated adenocarcinoma in the inner surface of the cyst and in the fibrous connective tissue of the hypertrophic cystic wall. The tumor cells were immunohistochemically reactive to cytokeratin (CK) 7, CK18 and CK20. No remnant of the malignancy was detected in the resected margin of the colon, cyst, liver or peritoneum nor was an uptake detected in an 18[F]-fluorodeoxyglucose positron emission tomography/CT examination of other organs. Finally, the malignancy was concluded to be a serous cystadenocarcinoma of the mesentery. Nineteen months after the operation, the patient died from peritonitis carcinomatosa due to a small intestine rupture. This report suggests mesenteric cystadenocarcinomas originating in the ovary, oviduct and intestinal mucosa, but these were ruled out in our patient. In this report, we discuss a case of the malignant transformation of a cyst into adenocarcinoma, which to our knowledge has never been previously reported in a male patient. PMID:24759353
Matulonis, Ursula A; Hirsch, Michelle; Palescandolo, Emanuele; Kim, Eejung; Liu, Joyce; van Hummelen, Paul; MacConaill, Laura; Drapkin, Ronny; Hahn, William C
Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology. The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥ 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population.
Showeil, Rania; Romano, Claudia; Valganon, Mikel; Lambros, Maryou; Trivedi, Pritesh; Van Noorden, Susan; Sriraksa, Ruethairat; El-Kaffash, Dalal; El-Etreby, Nour; Natrajan, Rachael; Foroni, Letizia; Osborne, Richard; El-Bahrawy, Mona
The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear
Smith, Ashlee L.; Sun, Mai; Bhargava, Rohit; Stewart, Nicolas A.; Flint, Melanie S.; Bigbee, William L.; Krivak, Thomas C.; Strange, Mary A.; Cooper, Kristine L.; Zorn, Kristin K.
Objective: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: After IRB approval, six patients with advanced HGSOC were identified with tumor in both ovaries at initial surgery. Laser capture microdissection (LCM) was used to extract tumor for protein digestion. Peptides were extracted and analyzed by reversed-phase liquid chromatography coupled to a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database. Differences in protein abundance between samples were assessed and analyzed by Ingenuity Pathway Analysis software. Immunohistochemistry (IHC) for select proteins from the original and an additional validation set of five patients was performed. Results: Unsupervised clustering of the abundance profiles placed the paired specimens adjacent to each other. IHC H-score analysis of the validation set revealed a strong correlation between paired samples for all proteins. For the similarly expressed proteins, the estimated correlation coefficients in two of three experimental samples and all validation samples were statistically significant (p < 0.05). The estimated correlation coefficients in the experimental sample proteins classified as differentially expressed were not statistically significant. Conclusion: A global proteomic screen of primary HGSOC tumors and their metastatic lesions identifies tumoral homogeneity and heterogeneity and provides preliminary insight into these protein profiles and the cellular pathways they constitute.
Background To report two cases of atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy. Case presentation Two patients with incidentally discovered abnormalities of the retina without specific symptoms were referred to our hospital for consultation. Bilateral macula atrophic lesions were observed and optical coherence tomography revealed serous retinal detachment in the macula. Fluorescein angiography showed multiple leakages around the central hypofluorescent area and indocyanine green angiography showed partially dilated choroidal vessels. Fundus autofluorescence (FAF) showed a decreasing pattern of autofluorescence in the subretinal fluid area, and increasing autofluorescence at the border of the serous retinal detachment. Both patients were diagnosed with chronic central serous chorioretinopathy. Photodynamic therapy and intravitreal bevacizumab injection were administered for engorged choroidal vessels during follow-up, but neither patient showed improvement in symptoms or ophthalmologic findings. Based on re-evaluation by fundus photography, optical coherence tomography, fluorescein angiography, and comparison of the results of FAF with the first visit, vitelliform macular dystrophy was suspected and a definite diagnosis was made by electrooculography and genetic testing. Conclusion In patients with continuous serous retinal detachment without response to photodynamic therapy or intravitreal bevacizumab injection, careful fundus exam and FAF can be used to diagnose atypical vitelliform macular dystrophy. PMID:22817759
Finkbeiner, Walter E.; Zlock, Lorna T.; Mehdi, Irum
There are two main epithelial cell types in the secretory tubules of mammalian glands: serous and mucous. The former is believed to secrete predominantly water and antimicrobials, the latter mucins. Primary cultures of human airway gland epithelium have been available for almost 20 yr, but they are poorly differentiated and lack clear features of either serous or mucous cells. In this study, by varying growth supports and media, we have produced cultures from human airway glands that in terms of their ultrastructure and secretory products resemble either mucous or serous cells. Of four types of porous-bottomed insert tested, polycarbonate filters (Transwells) most strongly promoted the mucous phenotype. Coupled with the addition of epidermal growth factor (EGF), this growth support produced “mucous” cells that contained the large electron-lucent granules characteristic of native mucous cells, but lacked the small electron-dense granules characteristic of serous cells. Furthermore, they showed high levels of mucin secretion and low levels of release of lactoferrin and lysozyme (markers of native serous cells). By contrast, growth on polyethylene terephthalate filters (Cyclopore) in medium lacking EGF produced “serous” cells in which small electron-dense granules replaced the electron-lucent ones, and the cells had high levels of lactoferrin and lysozyme but low levels of mucins. Measurements of transepithelial resistance and short-circuit current showed that both “serous” and “mucous” cell cultures possessed tight junctions, had become polarized, and were actively secreting Cl. PMID:19998060
WILKINSON, SALLYE M.; GABBARD, GLEN O.
The therapeutic use of countertransference disclosure as a means of highlighting the borderline patient’s intrapsychic and interpersonal use of the therapist is discussed. Countertransference disclosure is narrowly defined as a form of clinical honesty that focuses on the therapist’s experience of the patient in the here-and-now moment of the session. The effects of disclosure on transference exploration, neutrality, and patient revelations are explored through examination of detailed process notes of therapy sessions. Technical issues such as indirect versus direct disclosure and responses to direct questions are also addressed. PMID:22700154
Ayre, Karyn; Owen, Gareth S.; Moran, Paul
The use of the Mental Capacity Act 2005 in assessing decision-making capacity in patients with borderline personality disorder (BPD) is inconsistent. We believe this may stem from persisting confusion regarding the nosological status of personality disorder and also a failure to recognise the fact that emotional dysregulation and characteristic psychodynamic abnormalities may cause substantial difficulties in using and weighing information. Clearer consensus on these issues is required in order to provide consistent patient care and reduce uncertainty for clinicians in what are often emergency and high-stakes clinical scenarios. PMID:28184315
Biskin, Robert S
Borderline personality disorder (BPD) has historically been seen as a lifelong, highly disabling disorder. Research during the past 2 decades has challenged this assumption. This paper reviews the course of BPD throughout life, including childhood, adolescence, and adulthood. BPD can be accurately identified in adolescence, and the course of the disorder, in adolescence and adulthood, is generally similar, with reductions in symptoms over time. Functional recovery is less consistent, and further research on factors or treatments that may improve the long-term functional outcome of patients with BPD is warranted. PMID:26175388
Sansone, Randy A.; Wiederman, Michael W.; Sansone, Lori A.
Reviews possible links between obesity and borderline-personality disorder and discusses treatment approaches for those individuals demonstrating such comorbidity. Approaches include modification of current techniques for obesity treatment and incorporation of psychodynamic counseling specific to borderline-personality disorder. (Author/GCP)
Pretzer, James L.
Historically, the literature on psychotherapy with borderline personality disorder has been based on object-relations theory or psychoanalytical approaches, rather than cognitive and behavioral approaches. In clinical assessment, the term borderline has been used to refer to patients with both neurotic and psychotic symptoms, a particular type of…
Bernhardt, James Lawrence
This paper explores the findings and current state of research on the familial characteristics of persons with borderline personality disorder (BPD). A review of the borderline personality disorder emphasizes the development of the term, etiological issues, and treatment issues related to BPD. Two formal approaches for obtaining accurate diagnosis…
Sansone, Randy A.; Wiederman, Michael W.; Sansone, Lori A.
Reviews possible links between obesity and borderline-personality disorder and discusses treatment approaches for those individuals demonstrating such comorbidity. Approaches include modification of current techniques for obesity treatment and incorporation of psychodynamic counseling specific to borderline-personality disorder. (Author/GCP)
Fenning, Rachel M.; Baker, Jason K.; Baker, Bruce L.; Crnic, Keith A.
Parenting was examined among families of children with borderline intelligence in comparison to families of typically developing children and children with developmental delays. Parenting data were obtained at child age 5 via naturalistic home observation. Mothers of children with borderline intelligence exhibited less positive and less sensitive…
Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh
Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10(th) percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10(th) percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI.
PLAKUN, ERIC M.
Patients with borderline personality disorder often exhibit lethal or nonlethal self-destructive behavior. The author offers seven principles for establishing and maintaining a therapeutic alliance in the insight-oriented psychodynamic psychotherapy of borderline personality disorder patients with self-destructive behavior serious enough to threaten the continuity of the therapy. PMID:22700187
Flynn, Ciaran; Oxley, Jon; McCullagh, Paul; McCluggage, W Glenn
Serous carcinomas most commonly arise within the uterine corpus or ovary/fallopian tube, but there are 2 prior case reports of primary vaginal serous carcinoma. We report 2 examples of high-grade serous carcinoma arising within the urethra or a urethral diverticulum (1 case each). Both neoplasms exhibited the classic morphologic features of high-grade serous carcinoma, and a combination of clinical, radiologic, and pathologic examination excluded other possible sites of primary neoplasm.
Fonseca-Pedrero, Eduardo; Lemos-Giráldez, Serafín; Paino, Mercedes; Sierra-Baigrie, Susana; Muñiz, José
The main objective of the present investigation was to analyze the relationship between self-reported schizotypal and borderline personality traits in a sample of 759 college students (M = 19.63 years; SD = 2.03). For this purpose, the Schizotypal Personality Questionnaire-Brief (SPQ-B; Raine and Benishay, 1995) and Borderline Personality Questionnaire (BPQ; Poreh et al., 2006) were administered. The results showed that schizotypal and borderline features are partially related at subclinical level. The exploratory factor analysis conducted on the subscales revealed a three-factor solution comprised of the following factors: Identity/Interpersonal, Lack of Control and Schizotypal. The canonical correlation analysis showed that schizotypal features and borderline personality traits shared 34.8% of the variance. The data highlight the overlap between schizotypal and borderline personality traits in nonclinical young adults. Future studies should continue to examine the relationship and the degree of overlap between these traits in community samples.
Sansone, Randy A; Kelley, Amy R; Forbis, Jeremy S
The relationship between forgiveness and borderline personality symptomatology has been rarely studied. Using a consecutive cross-sectional sample of 307 internal medicine outpatients and a survey methodology, we examined correlations between the Forgiveness Scale and borderline personality symptomatology as measured by the borderline personality disorder scale of the Personality Diagnostic Questionnaire-4 and the Self-Harm Inventory. Numerous forgiveness subscales as well as the composite Forgiveness Scale score demonstrated statistically significant relationships with both measures for borderline personality symptomatology, such that individuals with this personality pathology demonstrated lower scores on these forgiveness subscales. Findings indicate that among individuals with borderline personality symptomatology, there are numerous aspects of forgiveness that are significantly lower than in individuals without this symptomatology.
Moisseiev, E; Holmes, A J; Moshiri, A; Morse, L S
PurposeTo evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC).MethodsRetrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded.ResultsInitial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 μm, and was significantly reduced after 1 month of treatment (284±77 μm; P=0.002) and this was maintained to the end of follow-up (247±85 μm; P=0.001). A signi