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Sample records for high-grade endometrial carcinomas

  1. Human epidermal growth factor receptor-2 overexpression and amplification in metastatic and recurrent high grade or type 2 endometrial carcinomas

    PubMed Central

    Kato, Rina; Hasegawa, Kiyoshi; Ishii, Risa; Owaki, Akiko; Torii, Yutaka; Oe, Shuko; Hirasawa, Hiroshi; Kobayashi, Yoichi; Udagawa, Yasuhiro

    2013-01-01

    Introduction Human epidermal growth factor receptor (HER)-2 overexpression or gene amplification is more common in high-grade or type 2 endometrial carcinomas. We assessed the discordance of HER-2 expression between primary and metastatic or recurrent endometrial carcinomas. Materials and methods Thirty-six primary, along with 14 metastatic and five recurrent tumors (matched to primaries), pathologically confirmed as high-grade or type 2 endometrial carcinomas, were submitted for immunohistochemistry (IHC) for HER-2. Fluorescence in situ hybridization was performed when the tumors showed HER-2 overexpression (≥2+ IHC score). The results of the IHC and fluorescence in situ hybridization assays were compared between the primary and metastatic or recurrent tumors. The relationships between HER-2 expression and clinicopathological factors or prognosis were investigated. Results HER-2 overexpression and HER-2 amplification (a ratio of HER-2 copies to chromosome 17 [CEP17] copies ≥2.2) were detected in 33.3% (twelve of 36 patients) and 5.6% (two of 36 patients) of primary tumors, respectively. HER-2 overexpression was not associated with clinicopathological factors or prognosis. In 19 tumor specimens obtained from metastatic or recurrent tumors, HER-2 overexpression and HER-2 amplification were detected in 57.9% (eleven patients) and 15.8% (three patients), respectively. HER-2 overexpression tended to predict a worse prognosis. Conclusion HER-2 expression in metastatic or recurrent tumors was more frequent than in matched primary high-grade or type 2 endometrial carcinomas. Trastuzumab in combination with cytotoxic chemotherapy may represent an alternative therapeutic option for these tumors. PMID:23950654

  2. Brain metastases from endometrial carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2012-01-01

    This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

  3. Endometrial carcinoma stage I.

    PubMed

    Baram, A; Ron, I; Kupferminc, M; Inbar, M

    1997-01-01

    Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately. PMID:21590195

  4. Estrogens and endometrial carcinoma.

    PubMed

    Gray, L A; Christopherson, W M; Hoover, R N

    1977-04-01

    A group of 205 women with endometrial carcinoma was matched for age, parity, and year of operation with a group of 205 women who had had hysterectomies for benign disease. In the former group, 32 patients had used conjugated estrogens, while in the latter group 12 had used this hormone, yielding a relative risk of 3.1 (P = 0.0008). Users of other forms of systemic estrogens showed similar elevations in relative risk. Relative risk was related to duration of use, progressing from no evidence of risk among those using the hormone for less than 5 years to an 11.5-fold greater risk for those using it for 10 years or more. Risk was also related to the strength of the medication. The relative risk for users of the 1.25-mg tablets was 12.7 as compared to a two- to fourfold greater risk among users of lesser strength tablets. PMID:193072

  5. Imaging in endometrial carcinoma

    PubMed Central

    Faria, Silvana C; Sagebiel, Tara; Balachandran, Aparna; Devine, Catherine; Lal, Chandana; Bhosale, Priya R

    2015-01-01

    Endometrial carcinoma (EC) is the most common gynecologic malignancy in the United States. Prognosis depends on patient age, histological grade, depth of myometrial invasion and/or cervical invasion, and the presence of lymph node metastases. Although EC is staged surgically according to the International Federation of Gynecology and Obstetrics (FIGO) system, preoperative imaging can assist in optimal treatment planning. Several imaging techniques such as transvaginal ultrasonography (TVUS), computed tomography (CT), and magnetic resonance imaging (MRI) have been used as diagnostic tools for preoperative staging of EC. Recently, positron emission tomography (PET), PET/CT, and PET/MRI have also been used in staging these patients. In this article, we review the value of imaging in diagnosis, staging, treatment planning, and detection of recurrent disease in patients with EC. PMID:25969637

  6. Integrated Genomic Characterization of Endometrial Carcinoma

    PubMed Central

    2013-01-01

    Summary We performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and ~25% of high-grade endometrioid tumors have extensive copy number alterations, few DNA methylation changes, low ER/PR levels, and frequent TP53 mutations. Most endometrioid tumors have few copy number alterations or TP53 mutations but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in the SWI/SNF gene ARID5B. A subset of endometrioid tumors we identified had a dramatically increased transversion mutation frequency, and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may impact post-surgical adjuvant treatment for women with aggressive tumors. PMID:23636398

  7. Endometrial carcinoma arising in a bicornuate uterus

    PubMed Central

    Munkhdelger, Jijgee; Mia-Jan, Khalilullah; Cha, Dong Soo

    2014-01-01

    Endometrial carcinomas arising in a bicornuate uterus are rare, only five case of which have been previously reported. We present a case of endometrial cancer arising in a bicornuate uterus, occurring in a 65-year-old woman. Unlike previously reported cases, our case showed mixed endometrial adenocarcinoma and undifferentiated carcinoma in one horn and focal adenocarcinoma in the other. Adequate tissue sampling of both horns is necessary for accurate diagnosis of malignancy in patients with a bicornuate uterus. Physicians should be aware of the possibility of this abnormality in cases when endometrial cancer is suspected but histology fails to confirm. PMID:25264532

  8. Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2013-01-23

    Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma

  9. Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

    ClinicalTrials.gov

    2014-09-09

    Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

  10. Endometrial carcinoma in elderly women.

    PubMed

    Hoffman, K; Nekhlyudov, L; Deligdisch, L

    1995-08-01

    Endometrial carcinoma remains the most common invasive gynecologic malignancy. Increased longevity is associated with an increased incidence of endometrial carcinoma (EC) in elderly women. While recent studies have looked at aging and its relation to ovarian, breast, and cervical cancer, few have focused on EC in the growing elderly population. This study analyzed 35 histologic specimens of EC in women 75-92 years of age. Findings revealed that only 23% of the tumors were Stage I, G1. The majority (77%) were deeply invasive or of advanced stage (IC-IV). These were G2, G3, or "virulent" types of nonendometrioid EC (undifferentiated, clear cell, uterine serous papillary, and squamous cell carcinoma). Fifty-seven percent of tumors were endometrioid, of which 9% were mixed, including a rare case of nongestational choriocarcinoma. The nonendometrioid tumors, compared to the endometrioid types, were more often high-stage tumors with vascular invasion. They were also more often associated with atrophic (vs hyperplastic) uninvolved endometrium. Clinical risk factors (nulliparity, obesity, estrogen replacement therapy) were assessed and correlated with the histologic findings. It was shown that tumors in the elderly were less likely to be estrogen-related. It was concluded that EC in this age group is more aggressive, histologically less differentiated, and often nonendometrioid compared with EC in the general population. The increased virulence of EC in the elderly may be related to the tumor's independence from hormonal factors, to the poorly understood but well-known diminished immunologic defense against cancer in general in elderly patients, and/or to the belated diagnosis of the disease in this population. PMID:7622105

  11. Temsirolimus in Treating Patients With Metastatic or Locally Advanced Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-02-05

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

  12. Mixed low grade and high grade endometrial stromal sarcoma of uterus: differences on immunohistochemistry and chromosome in situ hybridisation.

    PubMed Central

    Cheung, A N; Ng, W F; Chung, L P; Khoo, U S

    1996-01-01

    A case of a 64 year old woman with a tumour of the uterus is reported. The patient presented with postmenopausal bleeding and subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy. Sections of the tumour showed a low grade endometrial stromal sarcoma coexisting with areas consistent with high grade sarcoma. The sarcoma cells, in both the low and high grade areas, were positive for vimentin and negative for desmin and cytokeratin on immunohistochemistry. While the sarcoma cells in the low grade region showed immunoreactivity for oestrogen and progestogen receptors, those in the high grade region did not. Using chromosome in situ hybridisation, the low grade portion of the sarcoma was diploid for chromosomes X, 11, 12, and 17, whereas the more anaplastic areas were aneuploid for these chromosomes. This case may represent an example of high grade endometrial stromal sarcoma arising by dedifferentiation from a low grade stromal sarcoma. Adequate sampling is important in identifying such anaplastic changes as the origin of the tumour will affect patient management. Images PMID:8813967

  13. High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during pregnancy: a case report

    PubMed Central

    2010-01-01

    Introduction To the best of our knowledge, soft tissue sarcomas have not prevously been reported as a complication during pregnancy. Case presentation A 28-year-old Caucasian woman was diagnosed with a transperitoneal sarcoma during pregnancy. Morphological, immunohistochemical, chromosomal and mutational analyses pointed towards a high-grade endometrial stromal sarcoma. Although surgery and chemotherapy are possible during pregnancy, we were unable to perform these in this case. Conclusion The potential to treat gynecological cancer during pregnancy should always be assessed individually. PMID:20684773

  14. Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma

    PubMed Central

    Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran

    2014-01-01

    Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

  15. Primary Endometrial Squamous Cell Carcinoma In Situ

    PubMed Central

    Jetley, Sujata; Jairajpuri, Zeeba S.; Hassan, Mohammad J.; Madaan, Garima; Jain, Reena

    2015-01-01

    Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year’s duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up. PMID:26629388

  16. Vaginal implantation metastasis of endometrial carcinoma: A case report

    PubMed Central

    WANG, YUELING; DU, JIANG; LV, SHULAN; SUI, YANXIA; XUE, XUE; SUN, CHAO; ZOU, JUNKAI; MA, QUNYING; FU, GUOXING; SONG, QING; LI, QILING

    2016-01-01

    Endometrial cancer is the most common malignancy of the female reproductive system. The three common spread patterns of endometrial cancer are local invasion, lymphatic spread and hematogenous spread. Vaginal metastasis occurs by submucosal lymphatic or vascular metastases in ~10% of patients with clinical stage I disease. Vaginal implantation metastasis of endometrial cancer is extremely rare. Here we present a case of endometrial carcinoma (International Federation of Gynecology and Obstetrics stage IA) spread to the vagina by implantation metastasis as opposed to any of the methods mentioned above. This conclusion was confirmed mainly from pathological examination. This case highlights the occurrence of vaginal implantation metastasis of endometrial carcinoma. Certain changes may be applied during surgery to prevent implantation metastasis in patients with endometrial cancer. PMID:27347173

  17. Prevalence of Co-existing Endometrial Carcinoma in Patients with Preoperative Diagnosis of Endometrial Hyperplasia

    PubMed Central

    Kadirogullari, Pinar; Atalay, Cemal Resat; Sari, Mustafa Erkan

    2015-01-01

    Introduction Endometrial hyperplasia has been associated with the presence of concomitant endometrial carcinoma. In this study, patients who were diagnosed with endometrial hyperplasia and had hysterectomy, determination of the incidence of endometrial cancer accompanying postoperatively and clinical parameters associated with cancer are aimed. Materials and Methods Endometrial biopsies were taken from patients for various reasons and among them 158 patients diagnosed with endometrial hyperplasia from pathologic examination results were retrospectively evaluated. All of the patient’s age, parity, weight, transvaginal ultrasound measured by endometrial thickness, concomitant systemic disease (diabetes, hypertension, hypothyroidism), tamoxifen use, hormone use and whether in reproductive age or menopause were all questioned. Patients who applied with endometrial cancer, their cervical stromal involvement, lymph node involvement, cytology positivity and omental metastases were examined. Patients were classified according to their stage and grade. Patients who had intraoperative frozen were re-evaluated. Results Fifteen cases with preoperative endometrial hyperplasia diagnosed with endometrial cancer postoperatively, 2 cases had complex hyperplasia without atypia and 13 cases had complex atypical hyperplasia. The rate of preoperative hyperplasia with postoperative endometrial cancer was found to be 10.8% where by 15 cases of patients diagnosed with endometrial cancer postoperatively 11 cases were in postmenopausal period. In patients diagnosed with endometrial cancer according to their histologic types 14 cases had endometrioid adenocarcinoma while one patient with preoperative complex hyperplasia without atypia was diagnosed with serous papillary carcinoma postoperatively. Evaluation of stages in patients diagnosed with cancer, 7 cases of patients had stage IA, 7 cases of patients had stage IB, and 7 cases cases of patients with serous papillary carcinoma were

  18. Natural history of recurrences in endometrial carcinoma

    PubMed Central

    SORBE, BENGT; JURESTA, CHRISTIAN; AHLIN, CECILIA

    2014-01-01

    The aim of the present study was to evaluate the natural history of endometrial cancer recurrences with regard to predictive and prognostic factors. Between 1990 and 1999, 100 patients were treated for recurrences of endometrial carcinoma (all FIGO stages). Overall, 90 tumors were of endometrioid type. A total of 82 patients were treated with surgery, 41 patients received adjuvant external irradiation and 91 patients received vaginal brachytherapy. The median time to recurrence (TTR) was 32 months. The recurrences were treated using a combination of high-dose-rate brachytherapy and external pelvic irradiation in 35 cases. In addition, 44 patients were treated with chemotherapy and 21 patients received other types of therapy. The complete remission rate was 29% and the overall response rate was 44%. Among patients treated with radiotherapy, the response rate was 88% and, for those treated with chemotherapy, the rate was 33%. The local control of vaginal recurrences treated with combined radiotherapy was 93%. In 45 patients (45%) a second recurrence was identified and a third recurrence occurred in 12 patients. The overall five-year survival rate was 44%. Age, FIGO grade, nuclear grade, TTR and response to treatment were found to be independent and significant prognostic factors for overall survival rate. Locoregional recurrences were associated with a generalized extra-pelvic disease in 63% of the cases. PMID:25202413

  19. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    PubMed Central

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  20. Persistence of endometrial activity after radiation therapy for cervical carcinoma

    SciTech Connect

    Barnhill, D.; Heller, P.; Dames, J.; Hoskins, W.; Gallup, D.; Park, R.

    1985-12-01

    Radiation therapy is a proved treatment for cervical carcinoma; however, it destroys ovarian function and has been thought to ablate the endometrium. Estrogen replacement therapy is often prescribed for patients with cervical carcinoma after radiation therapy. A review of records of six teaching hospitals revealed 16 patients who had endometrial sampling for uterine bleeding after standard radiation therapy for cervical carcinoma. Fifteen patients underwent dilatation and curettage, and one patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy when a dilatation and curettage was unsuccessful. Six patients had fibrosis and inflammation of the endometrial cavity, seven had proliferative endometrium, one had cystic hyperplasia, one had atypical adenomatous hyperplasia, and one had adenocarcinoma. Although the number of patients who have an active endometrium after radiation therapy for cervical carcinoma is not known, this report demonstrates that proliferative endometrium may persist, and these patients may develop endometrial hyperplasia or adenocarcinoma. Studies have indicated that patients with normal endometrial glands have an increased risk of developing endometrial adenocarcinoma if they are treated with unopposed estrogen. Patients who have had radiation therapy for cervical carcinoma should be treated with estrogen and a progestational agent to avoid endometrial stimulation from unopposed estrogen therapy.

  1. PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women.

    PubMed

    Gbelcová, H; Bakeš, P; Priščáková, P; Šišovský, V; Hojsíková, I; Straka, Ľ; Konečný, M; Markus, J; D'Acunto, C W; Ruml, T; Böhmer, D; Danihel, Ľ; Repiská, V

    2015-01-01

    Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar. PMID:26114084

  2. Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2016-08-24

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma

  3. Clinically occult tubal and ovarian high-grade serous carcinomas presenting in uterine samples: diagnostic pitfalls and clues to improve recognition of tumor origin.

    PubMed

    Bagby, Christina; Ronnett, Brigitte M; Yemelyanova, Anna; Maleki, Zahra; Kuhn, Elisabetta; Vang, Russell

    2013-09-01

    We report the clinicopathologic and immunohistochemical features in 8 patients with tubal or ovarian high-grade serous carcinoma that was present in uterine samples, in which there was the potential for clinical and morphologic misinterpretation as a primary uterine lesion before hysterectomy/bilateral salpingo-oophorectomy. Patients ranged in age from 45 to 70 yr (mean, 57 yr). The initial presentation was variable, ranging from incidental findings on routine Pap smears to pleural effusion. During the preoperative clinical investigation, 7 of 8 patients did not have evidence of an adnexal tumor based on physical examination and radiologic imaging, and serum CA-125 levels were normal to low in 4 of 5 patients. Six patients required multiple rounds of uterine samples, and the preoperative uterine specimens that contained lesional tissue and were available for rereview in all 8 patients included endometrial biopsies/curettages (n=6), endocervical curettages (n=3), Pap smears (n=2), and a hysteroscopic myomectomy specimen (n=1). The amount of carcinoma in these specimens was typically scanty. The lesions in most cases were characterized by detached and minute epithelial clusters, small papillae, and/or individual cells. The constituent glandular cells exhibited notable atypia. Psammoma bodies were identified in only 2 cases. Immunostains for WT-1 were positive in 3 of 4 preoperative specimens. All patients ultimately underwent a hysterectomy/bilateral salpingo-oophorectomy, which revealed an invasive high-grade serous carcinoma of tubal (n=6) or ovarian (n=2) origin. The mean/median tumor size was 3.2/1.7 cm. Transtubal spread was considered the most likely mechanism resulting in tubal/ovarian carcinoma being found in the preoperative uterine samples. These findings highlight the deceptive clinical features of some tubal/ovarian high-grade serous carcinomas, and demonstrate that small and clinically undetectable adnexal high-grade serous carcinomas can initially

  4. Efficacy of microwave ablation for the treatment of endometrial carcinoma: A report of 3 cases

    PubMed Central

    NAKAMURA, KOHEI; NAKAYAMA, KENTARO; ISHIKAWA, MASAKO; KATAGIRI, HIROSHI; ISHIBASHI, TOMOKA; SATO, EMI; AMANO, CHIKA; KYO, SATORU

    2016-01-01

    Microwave endometrial ablation (MEA) is effective for the emergency control of uterine hemorrhage. However, to the best of our knowledge, there has been only a single report of life-threatening hemorrhage induced by endometrial carcinoma that was treated with MEA. The present report evaluates the efficacy of MEA as an emergency therapeutic option for the control of bleeding due to advanced endometrial carcinoma and minimally-invasive, early-stage endometrial carcinoma in 3 patients. MEA was able to effectively control massive uterine bleeding due to endometrial carcinoma in 2 patients with advanced disease and was curative in a patient with minimally-invasive endometrial carcinoma. Given its safety, simplicity and effectiveness, MEA may be utilized for the emergency treatment of uterine bleeding in advanced endometrial carcinoma, and may be used as a curative treatment in early-stage endometrial carcinoma. PMID:27123057

  5. Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-03-30

    Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

  6. Endometrial thickness and risk of breast and endometrial carcinomas in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Felix, Ashley S.; Weissfeld, Joel L.; Pfeiffer, Ruth M.; Modugno, Francesmary; Black, Amanda; Hill, Lyndon M.; Martin, Jerry; Sit, Anita S.; Sherman, Mark E.; Brinton, Louise A.

    2013-01-01

    Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, we tested the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55–74, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We evaluated associations between endometrial thickness and breast (n=91) and endometrial (n=14) carcinoma by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3–13.8 years). Compared to baseline endometrial thickness of 1.0 – 2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR: 2.00, 95% CI 1.15, 3.48) and endometrial (RR: 5.02, 95% CI 0.96, 26.36) carcinomas in models adjusted for menopausal hormone use and BMI. Our data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas. PMID:23907658

  7. Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

    PubMed

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P; Veras, Emanuela; Park, Kay J; Soslow, Robert A

    2016-03-01

    (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC. PMID:26551621

  8. The clinical management of inoperable endometrial carcinoma.

    PubMed

    Palisoul, Marguerite; Mutch, David G

    2016-05-01

    Unresectable endometrial cancer, while rare, has a very poor prognosis, with a survival rate of 2 to 8 months. Although endometrial cancer is generally regarded as a survivable disease, the less common advanced and aggressive forms account for a large portion of endometrial cancer related deaths. Given the paucity of inoperable disease, randomized clinical data is lacking in this specific patient population. Management decisions regarding radiation therapy or systemic therapy are largely guided by the existing data in the setting of recurrence or second-line treatment, adjuvant therapy following optimal debulking, or in patients who are considered inoperable due to medical comorbidities rather than the extent of their disease. PMID:26999568

  9. Genomic profiling of high-grade large-cell neuroendocrine carcinoma of the colon

    PubMed Central

    Hammond, William A.; Crozier, Jennifer A.; Nakhleh, Raouf E.

    2016-01-01

    High-grade neuroendocrine carcinoma (HGNEC) of the colon is a rare and aggressive cancer that has a poor prognosis. Currently no standard treatment exists, and published case series report an overall survival of approximately one year with treatment. Typically patients receive treatment similar to that recommended for small-cell lung cancer, extrapolating from the similarity in cancer biology. Here we report a case of HGNEC of the colon with genomic profiling that identified a KRAS G12D mutation and a PI3K mutation that has not yet been reported in the literature for this tumor type. PMID:27034803

  10. Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

    ClinicalTrials.gov

    2014-10-09

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage III Endometrial Carcinoma; Stage IV Endometrial Carcinoma

  11. Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality.

    PubMed

    Anglesio, Michael S; Wang, Yi Kan; Maassen, Madlen; Horlings, Hugo M; Bashashati, Ali; Senz, Janine; Mackenzie, Robertson; Grewal, Diljot S; Li-Chang, Hector; Karnezis, Anthony N; Sheffield, Brandon S; McConechy, Melissa K; Kommoss, Friedrich; Taran, Florin A; Staebler, Annette; Shah, Sohrab P; Wallwiener, Diethelm; Brucker, Sara; Gilks, C Blake; Kommoss, Stefan; Huntsman, David G

    2016-06-01

    Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination. PMID:26832771

  12. Mixed low- and high-grade papillary urothelial carcinoma: histopathogenetic and clinical significance.

    PubMed

    Mai, Kien T; Flood, Trevor A; Williams, Phillip; Kos, Zuzana; Belanger, Eric C

    2013-10-01

    There are two pathways of urothelial carcinogenesis: low-grade urothelial carcinoma (LGUC) with low rates of gene alterations and high-grade urothelial carcinoma (HGUC) with numerous gene alterations. HGUC often displays strong reactivity for cytokeratin 20 (CK20) and p16. Despite distinct molecular changes, urothelial carcinoma (UC) with both low- and high-grade features is not uncommon. We examined cases with patterns of mixed low- and high-grade UC (MLHGUC). Consecutive cases of UC at our institution were reviewed. There were 45 cases that showed a mixture of both LGUC and HGUC. IHC for CK5, CK20, CD44, p16, and Ki67 was performed. Areas of HGUC displayed strong and diffuse reactivity for p16, CK20, and Ki67 in 20-50 % of the tumor, while LGUC areas had negative or focal reactivity for CK20 and Ki67 in 10-30 %. There were two distinct cohorts of MLHGUC: patients with a history of LGUC (group A) and those without (group B). Group A patients (n = 8) had a history of LGUC for 1-10 years. The tumor specimens weighed 1.5 ± 1.7 g and had HGUC components of 25 ± 20 % of the tissue. Superficial invasion was present in one case. All tumors had BCG treatment with one recurrence. In group B (n = 37), tumor specimens weighed 3 ± 3.9 g and had HGUC components in 43 ± 21 % of the tissue. Superficial invasion was present in five cases, and muscle invasion with lung metastasis occurred in one case. Four cases were refractory to BCG with an increased proportion of HGUC, and one case requiring cystectomy. Differences in size and proportion of HGUC between groups A and B MLHGUC were significant (P < 0.05), with group B presenting with a higher tumor burden and proportion of HGUC. MLHGUC is diagnostically challenging and is commonly assigned high grade since this determines prognosis. Group A MLHGUC likely develops as a result of progression from LGUC, whereas group B MLHGUC likely develops de novo, is associated with larger tumors, shows a

  13. Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

    SciTech Connect

    Joshi, Ayesha; Ellenson, Lora Hedrick

    2011-07-01

    Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten{sup +/-} mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten{sup +/-} mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ER{alpha} as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.

  14. Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2016-03-16

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma

  15. Testicular Metastasis of a Upper Urinary Tract High-grade Papillary Urothelial Carcinoma, 2 Years After Nephroureterectomy

    PubMed Central

    Kubiak, M.; Klein, J.; de Perrot, T.; Tille, J.C.; Iselin, C.E.

    2015-01-01

    Urothelial carcinomas are the fourth most common tumors in men. Upper tract urinary carcinomas (UTUCs) are uncommon and represent only 5–10% of urothelial carcinomas.1 Metastatic testicular cancers are rare and primary tumor sources are the prostate, lung, and gastrointestinal tract. We report the first case of testicular metastasis 2 years after initial curative surgery for a high-grade UTUC, all other reported cases weren't proceed by curative surgery.3 PMID:26793571

  16. Pathology and Surgical Treatment of High-Grade Pancreatic Neuroendocrine Carcinoma: an Evolving Landscape.

    PubMed

    Haugvik, Sven-Petter; Kaemmerer, Daniel; Gaujoux, Sebastien; Labori, Knut Jørgen; Verbeke, Caroline Sophie; Gladhaug, Ivar Prydz

    2016-05-01

    Pancreatic neuroendocrine neoplasms (PNENs) are rare, accounting for less than 5 % of all pancreatic tumors. High-grade pancreatic neuroendocrine carcinomas (hgPNECs) represent about 5 % of all PNENs. They show highly aggressive behavior with dismal prognosis. Throughout the last two decades, there has been a notable progress in basic and clinical research of PNENs and a therapeutic trend towards both more aggressive and minimally invasive surgery. Despite these advances, hgPNECs as a distinct clinical entity remains largely unexplored among surgeons. This review of current development in pathology reporting and surgical treatment of hgPNECs aims at increasing the awareness of an evolving field in pancreatic surgery. PMID:26984415

  17. Current Issues in the Diagnosis and Treatment of Endometrial Carcinoma

    PubMed Central

    Stubert, J.; Gerber, B.

    2016-01-01

    Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future. PMID:26941450

  18. Trebananib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-02-10

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Endometrioid Stromal Sarcoma; Recurrent Uterine Corpus Carcinoma

  19. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma.

    PubMed

    Kurman, R J

    2013-12-01

    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

  20. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1342018

  1. Esophagectomy for failed endoscopic therapy in patients with high-grade dysplasia or intramucosal carcinoma.

    PubMed

    Hunt, B M; Louie, B E; Dunst, C M; Lipham, J C; Farivar, A S; Sharata, A; Aye, R W

    2014-01-01

    Endoscopic therapy (ablation +/- endoscopic resection) for high-grade dysplasia and/or intramucosal carcinoma (IMC) of the esophagus has demonstrated promising results. However, there is a concern that a curable, local disease may progress to systemic disease with repeated endotherapy. We performed a retrospective review of patients who underwent esophagectomy after endotherapy at three tertiary care esophageal centers from 2006 to 2012. Our objective was to document the clinical and pathologic outcomes of patients who undergo esophagectomy after failed endotherapy. Fifteen patients underwent esophagectomy after a mean of 13 months and 4.1 sessions of endotherapy for progression of disease (53%), failure to clear disease (33%), or recurrence (13%). Initially, all had Barrett's, 73% had ≥3-cm segments, 93% had a nodule or ulcer, and 91% had multifocal disease upon presentation. High-grade dysplasia was present at index endoscopy in 80% and IMC in 33%, and some patients had both. Final pathology at esophagectomy was T0 (13%), T1a (60%), T1b (20%), and T2 (7%). Positive lymph nodes were found in 20%: one patient was T2N1 and two were T1bN1. Patients with T1b, T2, or N1 disease had more IMC on index endoscopy (75% vs. 18%) and more endotherapy sessions (median 6.5 vs. 3). There have been no recurrences a mean of 20 months after esophagectomy. Clinical outcomes were comparable to other series, but submucosal invasion (27%) and node-positive disease (20%) were encountered in some patients who initially presented with a locally curable disease and eventually required esophagectomy after failed endotherapy. An initial pathology of IMC or failure to clear disease after three treatments should raise concern for loco-regional progression and prompt earlier consideration of esophagectomy. PMID:23795720

  2. Clinicopathologic and Immunophenotypic Characterization of 25 Cases of Acinic Cell Carcinoma with High-Grade Transformation.

    PubMed

    Thompson, Lester D; Aslam, Muhammad N; Stall, Jennifer N; Udager, Aaron M; Chiosea, Simion; McHugh, Jonathan B

    2016-06-01

    Acinic cell carcinoma (AiCC) with high-grade transformation is a rare variant of AiCC composed of both a conventional low-grade (LG) AiCC and a separate high-grade (HG) component. We describe here, the clinicopathologic and immunohistochemical features of 25 cases diagnosed between 1990 and 2015. Available tissue was analyzed and compared with a cohort of pure LG AiCC for the morphologic and immunophenotypic profile. Incidence was higher in females (1.8:1) than males with an overall mean age at presentation of 63.2 years. All tumors occurred in the parotid gland including 76 % with facial nerve trunk and branches involvement. Most patients were treated with extensive resection and adjuvant therapy. Local recurrence or distant metastasis occurred in most patients, with 72.7 % dead with disease (mean 2.9 years) and 3 patients alive with disease (mean 2.4 years). The majority of the tumors were composed of a LG microcystic AiCC and a HG component consisting of invasive lobules of undifferentiated cells with predominantly solid, cribriform, and glandular patterns. Acinic differentiation was still present in HG areas but aggressive features such as perineural invasion (76 %), lymphovascular invasion (62 %), positive margins (72 %), high mitotic rate, atypical mitoses and/or comedonecrosis (86 %) were easily identified. Compared to the pure LG AiCC, the cases with HG transformation showed significantly increased expression of cyclin-D1, p53 and Ki-67. Most HG areas of AiCC expressed membranous β-catenin (92 %) and were negative for p63 (three cases were focally positive), S100, SMA, androgen, and estrogen receptors. DOG1 expression was present in all LG AiCC tested with retained expression in 91 % of cases with HG transformation, supporting acinic differentiation in the HG foci. Recognition of AiCC with high-grade transformation is imperative as more aggressive clinical management is warranted. PMID:26245749

  3. [Possibility of the combined use of tumor markers in endometrial carcinoma].

    PubMed

    Indraccolo, S R; Cecchi, A; Thodos, A; Brandi, S; Carta, G

    1991-10-01

    The Authors have studied the haematic levels of CA 125, CA 19-9, CA 50, CEA, TPA, alfa-feto-proteina e CA 15-3 in 24 women with endometrial carcinoma and in 28 healthy women. The results show that these markers are not useful for the screening of endometrial carcinoma. PMID:1722568

  4. A Molecular Portrait of High-Grade Ductal Carcinoma In Situ.

    PubMed

    Abba, Martin C; Gong, Ting; Lu, Yue; Lee, Jaeho; Zhong, Yi; Lacunza, Ezequiel; Butti, Matias; Takata, Yoko; Gaddis, Sally; Shen, Jianjun; Estecio, Marcos R; Sahin, Aysegul A; Aldaz, C Marcelo

    2015-09-15

    Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2(+)) displayed signatures characteristic of activated Treg cells (CD4(+)/CD25(+)/FOXP3(+)) and CTLA4(+)/CD86(+) complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. PMID:26249178

  5. YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells.

    PubMed

    Hua, G; Lv, X; He, C; Remmenga, S W; Rodabough, K J; Dong, J; Yang, L; Lele, S M; Yang, P; Zhou, J; Karst, A; Drapkin, R I; Davis, J S; Wang, C

    2016-04-28

    Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In this study, we found that the Hippo/Yes-associated protein (YAP) signaling pathway has a critical role in the initiation and progression of fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine-positive feedback loop to drive the progression of the FTSEC-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGF receptors (such as BGJ398) can provide a novel therapeutic strategy to treat fallopian tube and ovarian HGSC. PMID:26364602

  6. YAP Induces High-Grade Serous Carcinoma in Fallopian Tube Secretory Epithelial Cells

    PubMed Central

    Hua, Guohua; Lv, Xiangmin; He, Chunbo; Remmenga, Steven W.; Rodabough, Kerry J.; Dong, Jixin; Yang, Liguo; Lele, Subodh M.; Yang, Peixin; Zhou, Jin; Karst, Alison; Drapkin, Ronny I.; Davis, John S.; Wang, Cheng

    2015-01-01

    Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from Fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In the present study, we found that the Hippo/YAP signaling pathway plays a critical role in the initiation and progression of Fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous Fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation, and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine positive feedback loop to drive the progression of the FTSECs-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGFRs (such as BGJ398) can provide a novel therapeutic strategy to treat Fallopian tube and ovarian HGSC. PMID:26364602

  7. High-grade Neuroendocrine Carcinoma With Focal Squamous Metaplasia of Renal Pelvis Associated With Renal Calculus: Study of a Case

    PubMed Central

    Huang, Yan-Ping; Chen, Bin; Sun, Xiang-Zhou; Guo, Yan; Yang, Shi-Cong; Deng, Chun-Hua; Huang, Yi-Ran

    2014-01-01

    Mixed neuroendocrine and non-neuroendocrine type of tumor in renal pelvis is rare and presents a high-grade malignancy. We present a case report that a 57-year-old man had no history of small cell cancer but presented a high-grade neuroendocrine carcinoma with focal squamous metaplasia and multiple stones simultaneously in the right renal pelvis. The patient underwent nephroureterocystectomy 9 months before this presentation, with evidence of multiple metastatic tumors in various parts of the body. The case of mixed neuroendocrine tumor with stones in the renal pelvis carries a poor prognosis and poses a therapeutic challenge to urologists. PMID:26952913

  8. Endometrial Cancer: Comparison of Patients with Synchronous Primary Carcinoma of the Endometrium and Ovary vs. Endometrial Carcinoma with Ovarian Metastases

    PubMed Central

    Juhasz-Böss, I.; Fehm, T.; Becker, S.; Rothmund, R.; Krämer, B.; Staebler, A.; Wallwiener, D.; Solomayer, E. F.

    2012-01-01

    Purpose: The aim of our study was to investigate the rate of secondary carcinomas in patients with endometrial carcinoma (EC). In particular, we wanted to describe the subset of patients with endometrial and simultaneous ovarian carcinoma (OC), including outcomes. The study also compared patients with EC and ovarian metastasis with patients with EC and simultaneous OC. Patients and Methods: Data from 251 patients with primary endometrial carcinoma who underwent surgery in the years 2005–2009 at the Department of Obstetrics and Gynaecology, University of Tübingen, were analysed retrospectively. Results: A total of 28 patients (11.1 %) had a secondary carcinoma: 18 patients (7.1 %) had OC; 9 (3.5 %) patients had a history of breast cancer, and one patient (0.4 %) respectively had simultaneous carcinoma of the vulva or bladder. 14 patients (5.5 %) had advanced stage EC with ovarian metastasis or, in one case, metastasis to the ovarian tube. Patients with ovarian metastasis had a mean age of 71.2 ± 9.2 years at primary diagnosis, making them significantly older compared to patients with EC and simultaneous OC (55.3 ± 11.8 years, p < 0.001). Moreover, patients with ovarian metastasis significantly more often had EC with a higher tumour grade (grade 1: 0, grade 2: 21.4 %, grade 3: 78.6 %) compared to patients with simultaneous EC and OC (grade 1: 11.1 %, grade 2: 77.8 %, grade 3: 11.1 %; p < 0.001). Conclusion: Almost one in 10 patients with EC had a secondary carcinoma. The most common secondary carcinoma was OC followed by breast cancer. This should be taken into account in the diagnosis and therapy of patients with EC. Patients with simultaneous EC and OC were significantly younger than patients with EC and ovarian metastasis. In addition, their tumour had better prognostic features: thus, the tumour grade of the EC was significantly lower. Overall, the prognosis for patients with synchronous EC and OC is better than that for

  9. Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma

    PubMed Central

    Haldorsen, Ingfrid S.; Brekke, Njål; Kopperud, Reidun; Visser, Nicole C.; Rygh, Cecilie B.; Pavlin, Tina; Salvesen, Helga B.; McCormack, Emmet; Krakstad, Camilla

    2015-01-01

    Background Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy. Methods After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography–computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing 18F-fluorodeoxyglocose (18F-FDG) or 18F- fluorothymidine (18F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer. Results Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in 18F-FDG and 18F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. 18F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue. Conclusions We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, 18F-FDG and 18F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models. PMID:26252891

  10. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    SciTech Connect

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-11-01

    A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with (17 alpha-methyl-TH)promegestone ((TH)R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of (3H)R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of (TH)R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V.

  11. Cervical Lymph Node Metastasis in High-Grade Transformation of Head and Neck Adenoid Cystic Carcinoma: A Collective International Review.

    PubMed

    Hellquist, Henrik; Skálová, Alena; Barnes, Leon; Cardesa, Antonio; Thompson, Lester D R; Triantafyllou, Asterios; Williams, Michelle D; Devaney, Kenneth O; Gnepp, Douglas R; Bishop, Justin A; Wenig, Bruce M; Suárez, Carlos; Rodrigo, Juan P; Coca-Pelaz, Andrés; Strojan, Primož; Shah, Jatin P; Hamoir, Marc; Bradley, Patrick J; Silver, Carl E; Slootweg, Pieter J; Vander Poorten, Vincent; Teymoortash, Afshin; Medina, Jesus E; Robbins, K Thomas; Pitman, Karen T; Kowalski, Luiz P; de Bree, Remco; Mendenhall, William M; Eloy, Jean Anderson; Takes, Robert P; Rinaldo, Alessandra; Ferlito, Alfio

    2016-03-01

    Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation. PMID:26895332

  12. Ovarian Yolk Sac Tumor With High-Grade Serous Carcinoma in a 62-Year-Old Woman.

    PubMed

    McCarthy, Whitney A; Masand, Ramya P

    2016-06-01

    Ovarian yolk sac tumors are germ cell tumors that usually present in children and young women. Rarely, these tumors can arise in older women, usually in conjunction with surface epithelial tumors, suggesting divergent differentiation from the latter. The combination of mixed ovarian yolk sac tumor and high-grade serous carcinoma is rare, with only one case documented in the literature. We present a case of mixed ovarian yolk sac tumor and high-grade serous carcinoma in a postmenopausal woman, including a brief discussion of the immunohistochemical findings and differential diagnosis. Despite the rarity of mixed ovarian yolk sac tumor and surface epithelial tumors, it is important to recognize the biphasic nature of the tumor, which should prompt a thorough immunohistochemical evaluation. The therapeutic and prognostic implications of proper diagnosis cannot be overemphasized. PMID:26782153

  13. Endometrial evaluation by ultrasonography, hysteroscopy and histopathology in cases of breast carcinoma on Tamoxifen therapy

    PubMed Central

    Jindal, Alka; Mohi, Manjit K.; Kaur, Manjeet; Kaur, Balwinder; Singla, Risham; Singh, Shaunik

    2015-01-01

    Introduction: Tamoxifen, a nonsteroidal antiestrogenic agent, is used widely as adjunctive therapy for women with breast cancer. Most studies have found that the increased relative risk of developing endometrial cancer for women taking Tamoxifen is two to three times higher than that of an age-matched population. So we designed this study to assess the endometrial status in patients taking Tamoxifen for breast carcinoma. Material and Methods: The study was conducted at Govt. Medical College and Rajindra Hospital, Patiala, India. A total of 50 patients of Ca Breast taking Tamoxifen were selected as per study criterion and TVS performed. If endometrial thickness was more than 5 mm hysteroscopy and endometrial HPE was done and data analysed. Results: On ultrasonography 35 patients (70%) had an endometrial thickness up to 5 mm. 15 patients (30%) had an endometrial thickness more than 5mm. Out of these, 11 patients, i.e. 22% of total, had an endometrial thickness of 5.1 to 10 mm and 2 patients, i.e. 4% of total had an endometrial thickness of more than 20 mm. Hysteroscopy was done on 11 patients. Out of these 8 patients had a normal hysteroscopic appearance whereas 3 patients had an abnormal hysteroscopic picture. Endometrial HPE of these 11 patients revealed 2 patients had secretory changes, 1 had polyp change, 1 had atrophic endometrium, 3 had simple endometrial hyperplasia, 1 had endometrial adenocarcinoma and 4 patients were reported to have scanty curetting. Conclusion: The duration of Tamoxifen therapy turned out to have a relationship with the incidence of endometrial carcinoma (P < 0.0001). Also, a relationship was observed between the duration of Tamoxifen therapy and symptom status of the patients (P < 0.0001). This correlation did not extend to duration of Tamoxifen therapy and endometrial thickness. (P = 0.190). This correlation did not extend to duration of Tamoxifen therapy and endometrial thickness. (P = 0.190). PMID:26167055

  14. Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

  15. Well Differentiated Neuroendocrine Tumors with a Morphologically Apparent High Grade Component: A Pathway Distinct from Poorly Differentiated Neuroendocrine Carcinomas

    PubMed Central

    Tang, Laura H.; Untch, Brian R.; Reidy, Diane L.; O'Reilly, Eileen; Dhall, Deepti; Jih, Lily; Basturk, Olca; Allen, Peter J.; Klimstra, David S.

    2016-01-01

    Purpose Most well-differentiated neuroendocrine tumors (WD-NETs) of the enteropancreatic system are low-intermediate grade (G1,G2). Elevated proliferation demonstrated by either a brisk mitotic rate (>20/10 high power fields) or high Ki67 index (>20%) defines a group of aggressive neoplasms designated as high grade (G3) neuroendocrine carcinoma (NEC). High grade NEC is equated with poorly-differentiated NEC (PD-NEC) and is associated with a dismal outcome. Progression of WD-NETs to a high grade neuroendocrine neoplasm very rarely occurs and their clinicopathologic and molecular features need to be characterized. Methods We investigated the 31 cases of WD-NETs with evidence of component of a high grade neoplasm. The primary sites included pancreas, small bowel, bile duct, and rectum. Histopathology of the cases was retrospectively reviewed and selected immunohistochemistry and gene mutation analyses performed. Results The high grade component occurred either within the primary tumor (48%) or at metastatic sites (52%). The clinical presentation, radiographic features, biomarkers, and the genotype of these WD-NETs with high grade component remained akin to those of G1-G2 WD-NETs. The median disease specific survival (DSS) was 55 months (16-119 months), and 2-year and 5-year DSS was 88% and 49%, respectively – significantly better than that of a comparison group of true PD-NEC (DSS 11 months). Conclusion Mixed grades can occur in WD-NETs, which are distinguished from PDNECs by their unique phenotype, proliferative indices, and the genotype. This phenomenon of mixed grade in WD-NET provides additional evidence to the growing recognition that the current WHO G3 category contains both WD-NETs as well as PDNECs. PMID:26482044

  16. Enolase-1 is a therapeutic target in endometrial carcinoma

    PubMed Central

    Shu, Luyun; Wang, Lijing; Chen, YiYu; Fu, Qiaofen; Liu, Yan; Hua, Shengni; Fan, Yue; Liu, Yiyi; Deng, Xiaojie; Luo, Rongcheng; Mei, Zhong; Jiang, Qinping; Liu, Zhen

    2015-01-01

    ENO1 plays a paradoxical role in driving the pathogenesis of tumors. However, the clinical significance of ENO1 expression remains unclear and its function and modulatory mechanisms have never been reported in endometrial carcinoma (EC). In this study, ENO1 silencing significantly reduced cell glycolysis, proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo by modulating p85 suppression. This in turn mediated inactivation of PI3K/AKT signaling and its downstream signals including glycolysis, cell cycle progression, and epithelial-mesenchymal transition (EMT)-associated genes. These effects on glycolysis and cell growth were not observed after ENO1 suppression in normal human endometrial epithelial cells (HEEC). Knocking down ENO1 could significantly enhance the sensitivity of EC cells to cisplatin (DDP) and markedly inhibited the growth of EC xenografts in vivo. In clinical samples, EC tissues exhibited higher expression levels of ENO1 mRNA and protein compared with normal endometrium tissues. Patients with higher ENO1 expression had a markedly shorter overall survival than patients with low ENO1 expression. We conclude that ENO1 favors carcinogenesis, representing a potential target for gene-based therapy. PMID:25951350

  17. p53 alteration in morphologically normal/benign breast tissue in patients with triple-negative high-grade breast carcinomas: breast p53 signature?

    PubMed

    Wang, Xi; Stolla, Moritz; Ring, Brian Z; Yang, Qi; Laughlin, Todd S; Rothberg, Paul G; Skinner, Kristin; Hicks, David G

    2016-09-01

    p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor-negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple-negative high-grade invasive ductal carcinomas, 48 estrogen receptor (ER)-positive/progesterone receptor-positive/Her2-negative non-high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry staining for p53. TP53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 case had focal p53 staining in normal/benign tissue, but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki-67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the "p53 signature" in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma. PMID:27246177

  18. Results of radiotherapy in recurrent endometrial carcinoma: A retrospective analysis of 51 patients

    SciTech Connect

    Kuten, A.; Grigsby, P.W.; Perez, C.A.; Fineberg, B.; Garcia, D.M.; Simpson, J.R.

    1989-07-01

    A retrospective analysis was performed of 51 patients with locoregional recurrence of endometrial carcinoma, treated by radiotherapy between 1959 and 1986. There were 17 patients (33%) with isolated vaginal recurrence, 12 patients (24%) with vaginal recurrence with pelvic extension, 7 patients (14%) with pelvic recurrence only, and 15 patients (29%) with simultaneous locoregional and distant failure. Eighty percent of the recurrences occurred within 3.5 years from primary treatment; time to relapse was shorter in patients with advanced-stage, high-grade malignancy at original diagnosis. Locoregional control was achieved in 18 patients (35%). Complete tumor regression in the vagina, irrespective of extravaginal pelvic disease status or distant metastasis, occurred in 28 of 34 patients with vaginal involvement (82%). The 5- and 10-year overall actuarial survivals for all patients were 18 and 12.5%, respectively. The 5- and 10-year progression-free survivals of patients with isolated vaginal recurrences were 40% and 29%, respectively; the 5-year progression-free survival of patients with vaginal recurrence with pelvic extension was 20%. There were no survivors beyond 1.5 years among patients with pelvic recurrence (p = 0.02). All patients with simultaneous locoregional and distant failure were dead by 3.5 years. Stage at original diagnosis, time to relapse from primary treatment, histologic pattern, and grade of malignancy were prognosticators of survival. Five patients (10%) developed a total of ten radiation-related sequelae.

  19. MiR-29a is a candidate biomarker of better survival in metastatic high-grade serous carcinoma.

    PubMed

    Nymoen, Dag Andre; Slipicevic, Ana; Holth, Arild; Emilsen, Elisabeth; Hetland Falkenthal, Thea E; Tropé, Claes G; Reich, Reuven; Flørenes, Vivi Ann; Davidson, Ben

    2016-08-01

    The objective of this study was to analyze the clinical role of 9 microRNAs (miRs) previously found to be overexpressed in ovarian carcinoma effusions compared with primary ovarian carcinomas. High-grade serous carcinoma effusions (n=148) were analyzed for expression of miR-29a, miR-31, miR-99b, miR-182, miR-210, miR-221, miR-222, miR-224, and miR-342 using quantitative polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters and survival. miR-29a and miR-31 levels were further assessed for association with protein expression of their targets Stathmin and DNA methyltransferase-3A (DNMT3A) by immunohistochemistry and Western blotting, respectively. miRNA levels were unrelated to clinicopathological parameters. However, higher miR-29a levels were significantly related to longer overall survival in univariate (P=.007) and Cox multivariate survival analysis (P=.045). miR-29a levels were inversely related to those of its target DNMT3A (P=.048), and higher DNMT3A expression was significantly related to poor overall survival in univariate (P=.03) and Cox multivariate (P=.016) survival analysis. In contrast, miR-31 levels were directly related to cytoplasmic phospho-Stathmin expression (P=.029) and unrelated to Stathmin and nuclear phospho-Stathmin, and both Stathmin and phospho-Stathmin expressions were unrelated to survival. miR-29a and its target DNMT3A are novel candidate biomarkers of longer and shorter survival, respectively, in metastatic high-grade serous carcinoma. PMID:27063471

  20. High grade neuroendocrine carcinoma of the urinary bladder treated by radical cystectomy: a series of small cell, mixed neuroendocrine and large cell neuroendocrine carcinoma.

    PubMed

    Gupta, Sounak; Thompson, R Houston; Boorjian, Stephen A; Thapa, Prabin; Hernandez, Loren P Herrera; Jimenez, Rafael E; Costello, Brian A; Frank, Igor; Cheville, John C

    2015-10-01

    High grade neuroendocrine carcinomas (HGNEC) treated by cystectomy often carry an original diagnosis of typical urothelial carcinoma (UC). The correct diagnosis of HGNEC is critical in influencing the decision for early chemotherapy, potentially followed by cystectomy. The objective of this study was to characterise the features of HGNEC treated by radical cystectomy. The study consisted of 79 patients with HGNEC including small cell (68 patients), large cell neuroendocrine (LCNEC) (5 patients) and mixed neuroendocrine (mixed-NEC) carcinoma (6 patients) matched with 122 patients with UC, treated at our institution between 1987 and 2014. Morphometric analysis for cell and nuclear size as well as immunophenotyping for neuroendocrine markers and cell-cycle regulators were applied to tissue microarrays. Small cell, LCNEC and mixed-NEC are a morphological spectrum of high grade neuroendocrine carcinoma with overlapping histological features, identical immunophenotype, Ki-67 proliferative rate and patient outcomes. Finally, the nuclear size criteria is misleading as HGNEC, particularly cases of LCNEC and mixed-NEC, may have enlarged nuclei compared to small cell carcinomas and are more prone to be misdiagnosed as UC, thereby preventing appropriate management. PMID:26308137

  1. Combined high-grade neuroendocrine carcinoma of the lung: clinicopathological and immunohistochemical study of 34 surgically resected cases.

    PubMed

    Yamada, Kenji; Maeshima, Akiko Miyagi; Tsuta, Koji; Tsuda, Hitoshi

    2014-01-01

    To understand the pathogenesis of high-grade neuroendocrine carcinoma (HGNEC), we examined the histopathology and immunoreactivity against adenocarcinoma (AD), squamous cell carcinoma (SQ), and neuroendocrine markers in 34 cases with combined HGNEC. The 5 year overall survival rates of patients with combined small cell carcinoma (SCC) (n = 9) and combined large cell neuroendocrine carcinoma (LCNEC) (n = 25) were 33% and 75%, respectively (P = 0.011). Most of the patients were male (94%), smokers (94%), and had tumors located in the peripheral (94%) and upper lobe (65%) of the lung. Histopathologically, non-HGNEC components were predominantly ADs (65%) followed by SQs (26%). In combined HGNEC and AD, a lepidic AD component was found in 12 cases (48%). For the HGNEC components of combined HGNEC and AD, the incidence of positivity of thyroid transcription factor-1 (TTF-1) (8G7G3/1) and TTF1 (SPT24) were 64% and 91%, respectively. For HGNEC components of combined HGNEC and SQ, the incidence of positivity of 34βE12 and p63 were 22% and 11%, respectively. In conclusion, 48% of combined HGNEC and AD cases had a lepidic AD component, suggesting that HGNEC can develop in association with pre-existing AD. AD markers, but not SQ markers, were frequently retained through development of the HGNEC component. PMID:24471967

  2. Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target.

    PubMed

    Asaka, Ryoichi; Miyamoto, Tsutomu; Yamada, Yasushi; Ando, Hirofumi; Mvunta, David Hamisi; Kobara, Hisanori; Shiozawa, Tanri

    2015-12-01

    Sirtuin 1 (SIRT1), originally identified as a longevity gene, is induced by caloric restriction, and regulates various cellular functions including DNA repair, cell survival and metabolism via the deacetylation of target proteins such as histone and p53. These functions are considered to act dualistically as preventing or facilitating cancer. This study aimed to clarify the expression and role of SIRT1 in endometrial carcinoma. Because a high-calorie diet was a well-known risk factor for endometrial carcinoma, we first hypothesized that SIRT1 might be downregulated in normal endometrial glandular cells of obese women. However, no correlation was observed between the expression of SIRT1 and body mass index (BMI). In contrast, regardless of BMI, the immunohistochemical expression of SIRT1 was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (P<0.05), and its overexpression was associated with a shorter survival (P<0.05). Our experiments in vivo revealed that SIRT1 accelerated the proliferation of endometrial carcinoma cell lines (HHUA, HEC151, and HEC1B). SIRT1 overexpression significantly enhanced the resistance for cisplatin and paclitaxel in HHUA cells. Although p53 is an important target protein for SIRT1, the selective SIRT1 inhibitor (EX527) significantly suppressed the proliferation and cisplatin resistance of three endometrial carcinoma cell lines regardless of the p53 mutation status. In addition, SIRT1 overexpression in HHUA cells accelerated tumor growth and cisplatin resistance in nude mice, and EX527 significantly suppressed the growth of tumors of HHUA and HEC1B cells. No adverse effect of EX527 was observed in these mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy. PMID:26367491

  3. Let7a inhibits the growth of endometrial carcinoma cells by targeting Aurora-B.

    PubMed

    Liu, Ping; Qi, Meiyan; Ma, Chengbin; Lao, Guoying; Liu, Yu; Liu, Yan; Liu, Yingzi

    2013-08-19

    MicroRNAs negatively regulate target gene expression at the post-transcriptional level during carcinogenesis. Recent advances revealed that the expression levels of several miRNAs are up- or down-regulated in endometrial carcinoma (EC). Here we identify dysregulated miRNAs in EC and we elucidate the essential role of let-7a. The expression of 86 miRNAs in EC was found to be different from adjacent normal endometrial tissues. Moreover, miR-let-7 members are down-regulated in EC and let-7 miRNAs are highly associated with endometrial cancer. A functional investigation revealed that let-7a suppressed proliferation of HeLa cells by targeting Aurora-B. Let-7a also antagonizes Aurora-B functions in promoting carcinoma cell proliferation by down-regulating Aurora-B protein level. Let-7a could be applied for gene therapy against endometrial carcinogenesis. PMID:23769985

  4. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    SciTech Connect

    Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus; Schueler, Phillip; Herrmann, Markus Karl; Hennies, Steffen; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

    2011-04-01

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  5. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development.

    PubMed

    Sherman-Baust, Cheryl A; Kuhn, Elisabetta; Valle, Blanca L; Shih, Ie-Ming; Kurman, Robert J; Wang, Tian-Li; Amano, Tomokazu; Ko, Minoru S H; Miyoshi, Ichiro; Araki, Yoshihiko; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Morin, Patrice J

    2014-07-01

    Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histological analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal-appearing p53-positive epithelium that are similar to 'p53 signatures' in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these non-invasive precursor lesions, we also identified invasive adenocarcinoma in the ovaries of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and wild-type (WT) C57BL/6. One of these genes, Top2a, which encodes topoisomerase IIα, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and was specifically elevated in mouse STICs but not in the surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumourigenesis, as well as

  6. Vulvar melanoma and endometrial polyp following breast carcinoma: a case report.

    PubMed

    Shen, L; Zeng, F; Hong, L; Zhang, G; Mai, R

    2013-01-01

    The authors describe the occurrence of a 55-year-old female patient presenting with a vulvar melanoma, endometrial polyp, and a prior history of breast carcinoma excised from the left chest wall, radiotherapy, chemotherapy, and tamoxifen maintenance for two years. This case exemplified second primary vulvar melanoma following breast cancer and supported that radiotherapy might play a role in the onset of secondary cancer. This case report also emphasizes the onset of endometrial polyp induced by tamoxifen. PMID:23781599

  7. Curcumin suppresses migration and invasion of human endometrial carcinoma cells

    PubMed Central

    CHEN, QIAN; GAO, QING; CHEN, KUNLUN; WANG, YIDONG; CHEN, LIJUAN; LI, XU

    2015-01-01

    Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signal-regulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC. PMID:26622667

  8. Serous endometrial intraepithelial carcinoma: a case series and literature review

    PubMed Central

    Pathiraja, P; Dhar, S; Haldar, K

    2013-01-01

    Background Minimal uterine serous cancer (MUSC) or serous endometrial intraepithelial carcinoma (EIC) has been described by many different names since 1998. There have been very few cases reported in literature since EIC/MUSC was recognized as a separate entity. The World health Organization (WHO) Classification favors the term serous EIC. Although serous EIC is confined to the uterine endometrium at initial histology diagnosis, a significant number of patients could have distal metastasis at diagnosis, without symptoms. Serous EIC is considered as being the precursor of uterine serous cancer (USC), but pure serous EIC also has an aggressive behavior similar to USC. It is therefore prudent to have an accurate diagnosis and appropriate surgical staging. There are very few published articles in literature that discuss the pure form of serous EIC. The aim of this series is to share our experience and review evidence for optimum management of serous EIC. Patients and methods We report a series of five women treated in our institute in the last 3 years. We reviewed the relevant literature on serous EIC and various management strategies, to recommend best clinical practice. Conclusion Pure serous EIC is a difficult histopathological diagnosis, which requires ancillary immunohistochemical staining. It can have an aggressive clinical behavior with early recurrence and poor survival. Optimum surgical staging, with appropriate adjuvant treatment, should be discussed when treating these patients. PMID:23861597

  9. Long Non-Coding RNAs in Endometrial Carcinoma

    PubMed Central

    Smolle, Maria A.; Bullock, Marc D.; Ling, Hui; Pichler, Martin; Haybaeck, Johannes

    2015-01-01

    Endometrial carcinoma (EC), the second most common form of gynaecological malignancy, can be divided into two distinct sub-types: Type I tumours arise from hyperplastic endometrium and typically effect women around the time of menopause, whereas type II tumours arise in postmenopausal women from atrophic endometrium. Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding molecules that have recently been implicated in the pathogenesis of many types of cancer including gynaecological tumours. Although they play critical physiological roles in cellular metabolism, their expression and function are deregulated in EC compared with paired normal tissue, indicating that they may also participate in tumour initiation and progression. For instance, the lncRNA MALAT-1 is down-regulated in EC samples compared to normal or hyperplastic endometrium, whereas the lncRNA OVAL is down-regulated in type II disease but up-regulated in type I disease. Other notatble lncRNAs such as HOTAIR, H19 and SRA become up-regulated with increasing EC tumour grade and other features associated with poor prognosis. In the current review, we will examine the growing body of evidence linking deregulated lncRNAs with specific biological functions of tumour cells in EC, we will highlight associations between lncRNAs and the molecular pathways implicated in EC tumourigenesis and we will identify critical knowledge gaps that remain to be addressed. PMID:26556343

  10. Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity?

    PubMed

    Shia, Jinru; Tang, Laura H; Weiser, Martin R; Brenner, Baruch; Adsay, N Volkan; Stelow, Edward B; Saltz, Leonard B; Qin, Jing; Landmann, Ron; Leonard, Gregory D; Dhall, Deepti; Temple, Larissa; Guillem, Jose G; Paty, Philip B; Kelsen, David; Wong, W Douglas; Klimstra, David S

    2008-05-01

    Although small cell carcinoma of the gastrointestinal (GI) tract is well-recognized, nonsmall cell type high-grade neuroendocrine carcinoma (HGNEC) of this site remains undefined. At the current time, neither the World Health Organization nor American Joint Committee on Cancer includes this condition in the histologic classifications, and consequently it is being diagnosed and treated inconsistently. In this study, we aimed at delineating the histologic and immunophenotypical spectrum of HGNECs of the GI tract with emphasis on histologic subtypes. Guided primarily by the World Health Organization/International Association for the Study of Lung Cancer criteria for pulmonary neuroendocrine tumors, we were able to classify 87 high-grade GI tract tumors that initially carried a diagnosis of either poorly differentiated carcinoma with or without any neuroendocrine characteristics, small cell carcinoma, or combined adenocarcinoma-neuroendocrine carcinoma into the following 4 categories. The first was small cell carcinoma (n=23), which had features typical of pulmonary small cell carcinoma, although the cells tended to have a more round nuclear contour. The second was large cell neuroendocrine carcinoma (n=31), which had a morphology similar to its pulmonary counterpart and showed positive immunoreactivity for either chromogranin (71%) or synaptophysin (94%) or both. The third was mixed neuroendocrine carcinoma (n=11), which had intermediate histologic features (eg, cells with an increased nuclear/cytoplasmic ratio but with apparent nucleoli), and positive immunoreactivity for at least 1 neuroendocrine marker. The fourth was poorly differentiated adenocarcinoma (n=17). In addition, 5 of the 87 tumors showed either nonsmall cell type neuroendocrine morphology (n=3) or immunohistochemical reactivity for neuroendocrine markers (n=2), but not both. Further analysis showed that most HGNECs arising in the squamous lined parts (esophagus and anal canal) were small cell type (78

  11. Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

    PubMed Central

    Perlino, E.; Loverro, G.; Maiorano, E.; Giannini, T.; Cazzolla, A.; Napoli, A.; Fiore, M. G.; Ricco, R.; Marra, E.; Selvaggi, L.

    1998-01-01

    Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma. Images Figure 1 Figure 5 Figure 6 Figure 8 PMID:9579831

  12. Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

    PubMed

    Perlino, E; Loverro, G; Maiorano, E; Giannini, T; Cazzolla, A; Napoli, A; Fiore, M G; Ricco, R; Marra, E; Selvaggi, L

    1998-04-01

    Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma. PMID:9579831

  13. Oncocytoma-like renal tumor with transformation toward high-grade oncocytic carcinoma: a unique case with morphologic, immunohistochemical, and genomic characterization.

    PubMed

    Sirintrapun, Sahussapont J; Geisinger, Kim R; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L; Ghazalpour, Anatole; Bender, Ryan P; Gatalica, Zoran

    2014-10-01

    Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt-Hogg-Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the development of an

  14. High-grade urothelial carcinoma with squamous differentiation metastasizing to the tongue.

    PubMed

    Khurram, Syed A; Farthing, Paula M; Whitworth, Abigail; McKechnie, Alasdair J; Fernando, Malee

    2016-05-01

    Tumors metastasizing to the head and neck region are uncommon. Metastasis of urothelial carcinoma to the maxillofacial region is exceedingly rare and mostly involves the jaw. We present a case of urothelial carcinoma metastasizing to the tongue. Immunohistochemistry in conjunction with fluorescent in situ hybridization was used to confirm the relation between the primary and metastatic lesions, making it the first such reported case employing the UroVysion (Catalogue number 02 J27-025, Abbott Molecular Inc., Des Plaines, IL, USA) fluorescent in situ hybridization probe in a metastatic lesion in the head and neck region. PMID:26525101

  15. Adopting a Uniform Approach to Site Assignment in Tubo-Ovarian High-Grade Serous Carcinoma: The Time has Come.

    PubMed

    Singh, Naveena; Gilks, C Blake; Hirshowitz, Lynn; Wilkinson, Nafisa; McCluggage, W Glenn

    2016-05-01

    There is currently sufficient evidence that nonuterine high-grade serous carcinoma (HGSC) originates in the fallopian tube in the majority of cases, but this is not uniformly reflected in our diagnostic terminology. This is because there remains wide variation in awareness and acceptance of this evidence, which conflicts with traditional views on origin. Accurate disease classification is fundamental to routine clinical practice and research, particularly at a time when exciting new approaches to therapy, early detection, and prevention are appearing on the horizon. We feel the time has come to minimize individual and institutional variations in practice, and agree on an evidence-based approach to uniform terminology and primary site assignment. In this paper we put forward a proposal for a unified approach based on published research evidence and discuss the reasons why it is vital to agree on a uniform protocol. We propose the term "Tubo-ovarian HGSC" in preference to "pelvic" or "Müllerian," as it accurately reflects the origin of this disease in the vast majority of cases, and is unambiguous, distinguishing it clearly from uterine serous carcinoma and ovarian low-grade serous carcinomas. A detailed protocol for primary site assignment is presented for different scenarios, which is easy to follow and has been developed with a view to promoting a uniform approach worldwide. PMID:26977579

  16. Identification of HSPA8 as a candidate biomarker for endometrial carcinoma by using iTRAQ-based proteomic analysis

    PubMed Central

    Shan, Nianchun; Zhou, Wei; Zhang, Shufen; Zhang, Yu

    2016-01-01

    Although there are advances in diagnostic, predictive, and therapeutic strategies, discovering protein biomarker for early detection is required for improving the survival rate of the patients with endometrial carcinoma. In this study, we identify proteins that are differentially expressed between the Stage I endometrial carcinoma and the normal pericarcinous tissues by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. Totally, we screened 1,266 proteins. Among them, 103 proteins were significantly overexpressed, and 30 were significantly downexpressed in endometrial carcinoma. Using the bioinformatics analysis, we identified a list of proteins that might be closely associated with endometrial carcinoma, including CCT7, HSPA8, PCBP2, LONP1, PFN1, and EEF2. We validated the gene overexpression of these molecules in the endometrial carcinoma tissues and found that HSPA8 was most significantly upregulated. We further validated the overexpression of HSPA8 by using immunoblot analysis. Then, HSPA8 siRNA was transferred into the endometrial cancer cells RL-95-2 and HEC-1B. The depletion of HSPA8 siRNAs significantly reduced cell proliferation, promoted cell apoptosis, and suppressed cell growth in both cell lines. Taken together, HSPA8 plays a vital role in the development of endometrial carcinoma. HSPA8 is a candidate biomarker for early diagnosis and therapy of Stage I endometrial carcinoma. PMID:27110132

  17. Recurrent High-Grade Invasive Mucoepidermoid Carcinoma of Larynx: A Case Report and Review of the Literature.

    PubMed

    King, Whitney; Ko, Stephen; Miller, Daniel

    2016-06-28

    Recurrent invasive high-grade mucoepidermoid carcinoma of the larynx and hypopharynx is a rare occurrence. These tumors have been commonly associated with salivary gland tumors, most commonly the parotid gland. The patient usually presents with the following symptoms: hoarseness (if larynx is involved), or changes in voice character, sore throat, cough, odynophagia, dysphagia, otalgia, difficulty breathing, weight loss, lymphadenopathy. Here we present a case of a recurrent invasive high-grade mucoepidermoid carcinoma of larynx and hypopharynx. The patient was a 67-year-old male that originally presented in 2006. At that time he underwent a wide field laryngectomy, right thyroid lobectomy, and biopsy of the right digastric node. He was a clinical stage III, pT3N0M0. No adjuvant radiation therapy was given at that time. The patient remained asymptomatic until February 2014, when he presented with dysphagia and neck swelling. Positron emission tomography/computed tomography showed evidence of recurrence. The patient was treated with definitive intensity modulated radiation therapy (IMRT) with concurrent chemotherapy. Treatment for this disease is gathered by scattered case reports. If surgery is a possibility it is considered as first line therapy. Post-surgical radiation is then offered. However, in this case the recurrent tumor was located near the carotid artery, and thus surgery was not a possibility. Therefore, concurrent chemotherapy and radiation with IMRT and weekly cis-platinum was given. While the optimum combination of treatment has not yet been established because of the rarity of this cancer's location site, the current patient appeared to have an excellent response from the definitive IMRT and chemotherapy treatment. PMID:27441076

  18. Recurrent High-Grade Invasive Mucoepidermoid Carcinoma of Larynx: A Case Report and Review of the Literature

    PubMed Central

    King, Whitney; Ko, Stephen; Miller, Daniel

    2016-01-01

    Recurrent invasive high-grade mucoepidermoid carcinoma of the larynx and hypopharynx is a rare occurrence. These tumors have been commonly associated with salivary gland tumors, most commonly the parotid gland. The patient usually presents with the following symptoms: hoarseness (if larynx is involved), or changes in voice character, sore throat, cough, odynophagia, dysphagia, otalgia, difficulty breathing, weight loss, lymphadenopathy. Here we present a case of a recurrent invasive high-grade mucoepidermoid carcinoma of larynx and hypopharynx. The patient was a 67-year-old male that originally presented in 2006. At that time he underwent a wide field laryngectomy, right thyroid lobectomy, and biopsy of the right digastric node. He was a clinical stage III, pT3N0M0. No adjuvant radiation therapy was given at that time. The patient remained asymptomatic until February 2014, when he presented with dysphagia and neck swelling. Positron emission tomography/computed tomography showed evidence of recurrence. The patient was treated with definitive intensity modulated radiation therapy (IMRT) with concurrent chemotherapy. Treatment for this disease is gathered by scattered case reports. If surgery is a possibility it is considered as first line therapy. Post-surgical radiation is then offered. However, in this case the recurrent tumor was located near the carotid artery, and thus surgery was not a possibility. Therefore, concurrent chemotherapy and radiation with IMRT and weekly cis-platinum was given. While the optimum combination of treatment has not yet been established because of the rarity of this cancer’s location site, the current patient appeared to have an excellent response from the definitive IMRT and chemotherapy treatment. PMID:27441076

  19. Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Kannan, Kalpana; Kordestani, Gona Karimi; Galagoda, Anika; Coarfa, Cristian; Yen, Laising

    2015-01-01

    High-grade serous ovarian cancer (HGSC) is among the most lethal forms of cancer in women. By analyzing the mRNA-seq reads from The Cancer Genome Atlas (TCGA), we uncovered a novel cancer-enriched chimeric RNA as the result of splicing between MUC1, a highly glycosylated transmembrane mucin, TRIM46, a tripartite motif containing protein, and KRTCAP2, a keratinocyte associated protein. Experimental analyses by RT-PCR (reverse transcription PCR) and Sanger sequencing using an in-house cohort of 59 HGSC patient tumors revealed a total of six MUC1-TRIM46-KRTCAP2 isoforms joined by different annotated splice sites between these genes. These chimeric isoforms are not detected in non-cancerous ovaries, yet are present in three out of every four HGSC patient tumors, a significant frequency given the exceedingly heterogeneous nature of this disease. Transfection of the cDNA of MUC1-TRIM46-KRTCAP2 isoforms in mammalian cells led to the translation of mutant MUC1 fusion proteins that are unglycosylated and cytoplasmically localized as opposed to the cell membrane, a feature resembling the tumor-associated MUC1. Because the parental MUC1 is overexpressed in 90% of HGSC tumors and has been proposed as a clinical biomarker and therapeutic target, the chimeric MUC1-TRIM46-KRTCAP2 isoforms identified in this report could represent significantly better MUC1 variants for the same clinical utilities. PMID:26492273

  20. Combination of Diane-35 and Metformin to Treat Early Endometrial Carcinoma in PCOS Women with Insulin Resistance

    PubMed Central

    Li, Xin; Guo, Yan-Rong; Lin, Jin-Fang; Feng, Yi; Billig, Håkan; Shao, Ruijin

    2014-01-01

    Background: Young women with polycystic ovary syndrome (PCOS) have a high risk of developing endometrial carcinoma. There is a need for the development of new medical therapies that can reduce the need for surgical intervention so as to preserve the fertility of these patients. The aim of the study was to describe and discuss cases of PCOS and insulin resistance (IR) women with early endometrial carcinoma while being co-treated with Diane-35 and metformin. Methods: Five PCOS-IR women who were scheduled for diagnosis and therapy for early endometrial carcinoma were recruited. The hospital records and endometrial pathology reports were reviewed. All patients were co-treated with Diane-35 and metformin for 6 months to reverse the endometrial carcinoma and preserve their fertility. Before, during, and after treatment, endometrial biopsies and blood samples were obtained and oral glucose tolerance tests were performed. Endometrial pathology was evaluated. Body weight (BW), body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), insulin area under curve (IAUC), and homeostasis model assessment of insulin resistance (HOMA-IR) were determined. Results: Clinical stage 1a, low grade endometrial carcinoma was confirmed before treatment. After 6 months of co-treatment, all patients showed normal epithelia. No evidence of atypical hyperplasia or endometrial carcinoma was found. Co-treatment resulted in significant decreases in BW, BMI, TT, FAI, IAUC, and HOMA-IR in parallel with a significant increase in SHBG. There were no differences in the FSH and LH levels after co-treatment. Conclusions: Combined treatment with Diane-35 and metformin has the potential to revert the endometrial carcinoma into normal endometrial cells in PCOS-IR women. The cellular and molecular mechanisms behind this effect merit further investigation. PMID:24563672

  1. Mixed and Ambiguous Endometrial Carcinomas: A Heterogenous Group of Tumors With Different Clinicopathologic and Molecular Genetic Features.

    PubMed

    Espinosa, Iñigo; D'Angelo, Emanuela; Palacios, José; Prat, Jaime

    2016-07-01

    Besides endometrioid, serous, and clear cell carcinomas, there are endometrial carcinomas exhibiting mixed and ambiguous morphologic features. We have analyzed the immunophenotype (p53, p16, β-catenin, ER, HNF-1B, MLH1, and Ki-67) and mutational status (PTEN, KRAS, PIK3CA, and POLE) of 7 mixed carcinomas and 13 ambiguous carcinomas, all of them classified initially as mixed carcinomas. Only 2 of the 7 (28%) mixed carcinomas showed different immunophenotypes in different components. All but 2 tumors (5/7, 71%) overexpressed p53 and p16 and were negative for ER. Both carcinomas (2/7, 28%) showed a prominent micropapillary component that resembled an ovarian low-grade serous carcinoma and merged with villoglandular endometrioid carcinoma. The ambiguous carcinomas exhibited glandular architecture, high nuclear grade, and overlapping features of endometrioid and serous carcinomas. All tumors overexpressed p53 and p16, and the majority of cases (12/13, 92%) were negative for ER. KRAS mutations were identified in 3 of 7 (42%) mixed carcinomas, including the 2 cases with a "low-grade" serous-like component. PIK3CA mutations occurred in 2 (2/13, 15%) ambiguous carcinomas and PTEN mutations in 1 (1/7, 14%) mixed and 1 (1/13, 8%) ambiguous carcinoma. POLE exonuclease domain mutations were encountered in a case of mixed undifferentiated and well-differentiated (dedifferentiated) carcinoma. Two of the 7 (29%) mixed endometrial carcinomas and 5 of the 13 (38%) ambiguous carcinomas had extended beyond the pelvis (stages III and IV). Two of the 7 (29%) patients with mixed endometrial carcinoma and 6 of 12 (50%) patients with ambiguous endometrial carcinoma were alive with disease or had died of tumor. Our results show that, biologically, many so-called mixed carcinomas represent serous carcinomas with ambiguous morphology. Our series include 2 true mixed endometrial carcinomas with a "low-grade serous"-like component, microcystic, elongated, or fragmented features, KRAS mutations

  2. HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis

    PubMed Central

    Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

    2016-01-01

    Introduction Hypoxia-Inducible Factor 1α (HIF-1α) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake. Aim To evaluate the immunohistochemical expression of both HIF-1α and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type. Materials and Methods A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1α and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks. Statistical Analysis Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). Results HIF-1α was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1α expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1α H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1α staining in all cases of EC (p= 0.04). Conclusion The role of HIF-1α in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The

  3. E2Fs mediate a fundamental cell-cycle deregulation in high-grade serous ovarian carcinomas.

    PubMed

    De Meyer, T; Bijsmans, I T G W; Van de Vijver, K K; Bekaert, S; Oosting, J; Van Criekinge, W; van Engeland, M; Sieben, N L G

    2009-01-01

    Several studies described a role for the E2F/Rb pathway in ovarian serous carcinomas (SCAs). Since E2F/Rb pathway deregulation is a general hallmark of human cancer, it remains unclear whether this deregulation is of particular importance in SCAs or whether it reflects a common oncological feature. Here, we have clarified this issue by the examination of microarray expression profiles of SCAs and particularly by the comparison with another, less malignant, ovarian cancer type, serous borderline tumours (SBTs). Results were validated by quantitative RT-PCR, both on the microarray samples and on an independent panel, and TP53 mutation analysis was performed. This integrated analysis revealed a significant increase in the expression of the transcription factors E2F1 and E2F3 in SCAs, when compared to SBTs. This was associated with vast overexpression of E2F target genes in SCAs compared to SBTs. High-grade SCAs in particular exhibited a major deregulated E2F target expression pattern. Generally, overexpression of E2F targets in SCAs appeared to be well structured since those targets considered negative regulators of the cell cycle or promoters of apoptosis were usually not overexpressed in SCAs. Similar to E2F target deregulation, TP53 mutations were identified in SCA3s, to a lesser extent in SCA1s, and not in SBTs. These results suggest that a structured, generally up-regulated E2F transcription factor activity is associated with a global cell-cycle disturbance in high-grade SCAs and exceeds typical E2F/Rb pathway disruption in tumours, at least compared with SBTs. PMID:18991331

  4. [Obesity, body fat distribution and the incidence of breast, cervical, endometrial and ovarian carcinomas].

    PubMed

    Sönnichsen, A C; Lindlacher, U; Richter, W O; Schwandt, P

    1990-12-14

    The connection of body fat distribution (BFD) and the risk of developing mammary, cervical, endometrial or ovarian carcinoma was ascertained for 163 patients with carcinoma (mean age 49.9 [19-78] years) and 489 controls of comparable age and body-mass index. BFD was expressed as the ratio of waist and hip circumference (T/H ratio of 0.822 vs 0.781 and 0.826 vs 0.789, respectively; P less than 0.01). In premenopausal women with mammary or cervical carcinoma and in all postmenopausal women BFD was similar to that in the control subjects. A common cause of android obesity and ovarian or endometrial carcinoma may be a reduction of sex-hormone-binding globulins with an elevated serum level of free androgens and oestrogens. PMID:2257779

  5. MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy

    PubMed Central

    Ran, Xiaomin; Yang, Juan; Liu, Chaoxia; Zhou, Ping; Xiao, Linzhi; Zhang, Keqiang

    2015-01-01

    Endometrial carcinoma is the most common gynecological malignancy among women worldwide. Although treatment for EC has improved with the introduction of Paclitaxel (Tax) chemotherapy, the majority of patients will develop resistance to the treatment, leading to poor prognosis. One of the causes of chemoresistance is the increased ability to undergo autophagy. In this study, we identified that miR-218 was significantly down-regulated in Tax-resistant EC cells compared to the non-drug resistant cell lines, and overexpression of miR-218 sensitized paclitaxel resistant EC cells to paclitaxel. Moreover, we demonstrated that miR-218 directly binds to the 3’-UTR of HMGB1 gene. HMGB1 was upregulated in paclitaxel resistant EC cells, it mediated autophagy and contributed to chemotherapy resistance in endometrial carcinoma in vitro. HMGB1-mediated autophagy could be suppressed by miR-218 overexpression in Tax resistant EC cells. In summary, we determined the targeting role of miR-218 to HMGB1 and the regulation of miR-218 on the HMGB1-mediated cell autophagy during chemotherapy resistance in endometrial carcinoma cells. These results reveal novel potential role of miR-218 against chemotherapy resistance during the treatment of endometrial carcinoma. PMID:26261543

  6. [Endometrial adenocarcinoma and clear cell carcinoma in a young woman with polycystic ovarian syndrome: a case report].

    PubMed

    Niu, Jing; Liu, Nan; Liu, Guo-Bing

    2016-05-20

    A 26-year-old unmarried woman with irregular menstruation for 4 years was admitted for an intrauterine space-occupying mass. Pathological examination before surgery showed moderately to poorly differentiated endometrial adenocarcinoma. The patient underwent laparoscopically assisted epifascial panhysterectomy with bilateral salpingo-oophorectomy. Pathological examination of the surgical specimens reported moderately to poorly differentiated endometrial adenocarcinoma and stage II clear cell carcinoma. The patient then received chemotherapy and remained alive without evidence of recurrence. Young women with polycystic ovarian syndrome are at high risk of developing endometrial carcinoma, but concurrent clear cell carcinoma is rare. Careful evaluation before and after treatment are essential to improve the patients prognosis. PMID:27222196

  7. [Environmental and genetic risk factors for endometrial carcinoma].

    PubMed

    Sénéchal, Claire; Cottereau, Edouard; de Pauw, Antoine; Elan, Camille; Dagousset, Isabelle; Fourchotte, Virginie; Gauthier-Villars, Marion; Lae, Marick; Stoppa-Lyonnet, Dominique; Buecher, Bruno

    2015-03-01

    In France, endometrial cancer is at the first rank of gynecological cancers for cancer incidence, before ovarian and cervical cancers. In fact, the number of incident cases has been estimated to 7275 for the year 2012; the number of death due to endometrial cancer to 2025. This cancer is hormone-dependent and endogenous (reproductive factors) or exogenous (oral combined contraceptives, hormone replacement therapy) causes of exposition to estrogens are the major environmental risk factors for both types of endometrial cancers: type I or well-differentiated endometrioid adenocarcinomas; and type II including all other histological types: papillary serous adenocarcinomas, clear cell adenocarcinomas and carcinosarcomas, also known as malignant mixed Mullerian tumor, MMMT. Obesity, diabetes mellitus and adjuvant treatment of breast cancer with tamoxifen are also associated with an increased risk of endometrial cancer. Genetic factors may also be implicated in the pathogenesis of endometrial cancer either as "minor genetic factors" (susceptibility factors), which remain largely unknown and are responsible for the increased observed risk in relatives of women affected with endometrial cancer; or as major genetic factors responsible for hereditary forms and namely for Lynch syndrome whose genetic transmission is of autosomic dominant type. The appropriate recognition of Lynch syndrome is of critical importance because affected patients and their relatives should benefit from specific care. The aims of this review is to describe major environmental and genetic risk factors for endometrial cancer with specific attention to most recent advances in this field and to describe recommendations for care of at-risk women. PMID:25725922

  8. CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas.

    PubMed

    Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Nakamura, Kohei; Ishikawa, Masako; Katagiri, Hiroshi; Sato, Emi; Ishibashi, Tomoka; Iida, Kouji; Ishikawa, Noriyuki; Kyo, Satoru

    2016-02-01

    The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; p=0.0087) and lymphovascular space invasion (p=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (p=0.851), lymph node metastasis (p=0.078), body mass index (p=0.265), deep myometrial invasion (p=0.256), menopausal status (p=0.289) or patient age (p=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (p=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown

  9. Comparison of Two Combination Chemotherapy Regimens Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

    ClinicalTrials.gov

    2015-04-30

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Stage III Uterine Corpus Cancer

  10. Prior Tubal Ligation Might Influence Metastatic Spread of Nonendometrioid Endometrial Carcinoma

    PubMed Central

    Li, Mingxia; Li, Mingzhu; Zhao, Lijun; Wang, Zhiqi; Wang, Yue; Shen, Danhua; Wang, Jianliu; Wei, Lihui

    2016-01-01

    Objective The exfoliation of endometrial carcinoma might intraperitoneally spread through the fallopian tube. We analyzed the influence of prior tubal ligation (TL) in endometrial carcinoma to evaluate whether it can prevent the process and improve patients’ survival. Methods A total of 562 patients with a diagnosis of endometrial carcinoma at the Peking University People’s Hospital between July 1995 and June 2012 were enrolled in this study. The patients were divided into 2 groups based on the presence or absence of prior TL. International Federation of Gynecology and Obstetrics stage distributions, recurrence rates, survival status, and histopathological findings were compared between the 2 groups. Kaplan-Meier estimates and log-rank tests were used to compare the survival status based on TL in the overall population and stratified by histopathological subtypes and International Federation of Gynecology and Obstetrics stages. Cox models analysis was used to estimate the hazard ratios and 95% confidence intervals for associations between TL and carcinoma-specific mortality. All statistical tests were 2-sided. Results Of the 562 patients, 482 (85.7%) had a diagnosis of endometrioid and 80 patients (14.2%) with nonendometrioid carcinoma. Tubal ligation was associated with negative peritoneal cytology in the total population (P = 0.015) and in patients with endometrioid carcinomas (P = 0.02) but not help to reduce carcinoma-specific mortality (P = 0.095 and P = 0.277, respectively). In the nonendometrioid group, TL was not only associated with negative peritoneal cytology (P = 0.004) but also with lower stage (P < 0.001) and lower recurrence rate(P < 0.005), resulting in improved prognosis (P = 0.022). In Cox models analysis adjusted for covariates, TL was inversely associated with lower endometrial carcinoma-specific mortality (hazard ratio, 0.47; 95% confidence interval, 0.14–2.6). Conclusion Tubal ligation was associated with lower positive peritoneal

  11. Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes.

    PubMed

    Murakami, Ryusuke; Matsumura, Noriomi; Mandai, Masaki; Yoshihara, Kosuke; Tanabe, Hiroshi; Nakai, Hidekatsu; Yamanoi, Koji; Abiko, Kaoru; Yoshioka, Yumiko; Hamanishi, Junzo; Yamaguchi, Ken; Baba, Tsukasa; Koshiyama, Masafumi; Enomoto, Takayuki; Okamoto, Aikou; Murphy, Susan K; Mori, Seiichi; Mikami, Yoshiki; Minamiguchi, Sachiko; Konishi, Ikuo

    2016-05-01

    Recently, The Cancer Genome Atlas data revealed four molecular subtypes of high-grade serous ovarian carcinoma (HGSOC) exhibiting distinct prognoses. We developed four novel HGSOC histopathological subtypes by focusing on tumor microenvironment: mesenchymal transition, defined by a remarkable desmoplastic reaction; immune reactive by lymphocytes infiltrating the tumor; solid and proliferative by a solid growth pattern; and papilloglandular by a papillary architecture. Unsupervised hierarchical clustering revealed four clusters correlated with histopathological subtypes in both Kyoto and Niigata HGSOC transcriptome data sets (P < 0.001). Gene set enrichment analysis revealed pathways enriched in our histopathological classification significantly overlapped with the four molecular subtypes: mesenchymal, immunoreactive, proliferative, and differentiated (P < 0.0001, respectively). In 132 HGSOC cases, progression-free survival and overall survival were best in the immune reactive, whereas overall survival was worst in the mesenchymal transition (P < 0.001, respectively), findings reproduced in 89 validation cases (P < 0.05, respectively). The CLOVAR_MES_UP single-sample gene set enrichment analysis scores representing the mesenchymal molecular subtype were higher in paclitaxel responders than nonresponders (P = 0.002) in the GSE15622 data set. Taxane-containing regimens improved survival of cases with high MES_UP scores compared with nontaxane regimens (P < 0.001) in the GSE9891 data set. Our novel histopathological classification of HGSOC correlates with distinct prognostic transcriptome subtypes. The mesenchymal transition subtype might be particularly sensitive to taxane. PMID:26993207

  12. Treatment for Advanced and Recurrent Endometrial Carcinoma: Combined Modalities

    PubMed Central

    Rauh-Hain, J. Alejandro

    2010-01-01

    Women with recurrent or advanced endometrial cancer constitute a heterogeneous group of patients. Depending on previous treatment, women with recurrent endometrial cancer may be appropriate candidates for surgery, radiation therapy, hormonal therapy, or chemotherapy. Women with advanced stage disease at presentation may also be appropriate candidates for systemic and local therapies. We review the treatment options available to treat recurrent and locally advanced endometrial cancer. Treatment choice depends largely on the localization of disease, the patient’s performance status and previous treatment history, as well the tumor’s hormonal receptor status. Radiation therapy is appropriate for isolated vaginal recurrences in patients with no previous history of radiation therapy. Patients with recurrent low-grade tumors overexpressing estrogen and progesterone receptors may be treated with progestin therapy. Systemic therapy is appropriate for patients with disseminate recurrences or advanced stage disease at presentation, or for those with receptor-negative tumors. We review all these different treatment strategies available to patients with advanced or recurrent endometrial cancer. PMID:20660059

  13. Digital Mammography Screening: Does Age Influence the Detection Rates of Low-, Intermediate-, and High-Grade Ductal Carcinoma in Situ?

    PubMed

    Weigel, Stefanie; Hense, Hans W; Heidrich, Jan; Berkemeyer, Shoma; Heindel, Walter; Heidinger, Oliver

    2016-03-01

    Purpose To investigate the association between age at screening and detection rates for ductal carcinoma in situ (DCIS) separately for different nuclear grades after introduction of a population-based digital mammography screening program. Materials and Methods The retrospective study was approved by the ethics board and did not require informed consent. In 733 905 women aged 50-69 years who participated in a screening program for the first time in 2005-2008 (baseline examinations were performed with digital mammography), DCIS detection rates were determined for 5-year age groups (detection rates per 1000 women screened) to distinguish high-, intermediate-, and low-grade DCIS. Multivariable logistic regression was used to compare detection rates between age groups by adjusting for screening units (P < .05). Results There were 989 graded DCIS diagnoses among 733 905 women (detection rate, 1.35‰): 419 diagnoses of high-grade DCIS (detection rate, 0.57‰), 388 diagnoses of intermediate-grade DCIS (detection rate, 0.53‰), and 182 diagnoses of low-grade DCIS (detection rate, 0.25‰). Detection rate for types of DCIS combined increased significantly across age groups (50-54 years, detection rate of 1.15‰ [254 of 220 985 women]; 55-59 years, detection rate of 1.23‰ [218 of 177 782 women]; 60-64 years, detection rate of 1.34‰ [201 of 150 415 women]; and 65-69 years, detection rate of 1.71‰ [316 of 184 723 women]; P < .001). Of note, the detection rate for high-grade DCIS showed a significant increase with age (odds ratio, 1.18 per 5-year age group; P < .0001). The increase was lower for intermediate-grade DCIS (odds ratio, 1.11; P = .016) and not significant for low-grade DCIS (P = .10). Conclusion Total DCIS detection rates increase with age, mostly because of an increase in high- and intermediate-grade DCIS, which are precursor lesions that carry a higher risk for transition to more aggressive invasive breast cancer than low-grade DCIS. (©) RSNA, 2015

  14. A Clinical and Pathologic Comparison Between Stage-Matched Endometrial Intraepithelial Carcinoma and Uterine Serous Carcinoma

    PubMed Central

    Hou, June Y.; McAndrew, Thomas C.; Goldberg, Gary L.; Whitney, Kathleen

    2014-01-01

    Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic–pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC. PMID:24023030

  15. Comprehensive Mutation Profiling by Next-Generation Sequencing of Effusion Fluids From Patients With High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Shah, Ronak H.; Scott, Sasinya N.; Brannon, A. Rose; Levine, Douglas A.; Lin, Oscar; Berger, Michael F.

    2016-01-01

    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

  16. ADAM12 is a prognostic factor associated with an aggressive molecular subtype of high-grade serous ovarian carcinoma.

    PubMed

    Cheon, Dong-Joo; Li, Andrew J; Beach, Jessica A; Walts, Ann E; Tran, Hang; Lester, Jenny; Karlan, Beth Y; Orsulic, Sandra

    2015-07-01

    ADAM metallopeptidase domain 12 (ADAM12) is a promising biomarker because of its low expression in normal tissues and high expression in a variety of human cancers. However, ADAM12 levels in ovarian cancer have not been well characterized. We previously identified ADAM12 as one of the signature genes associated with poor survival in high-grade serous ovarian carcinoma (HGSOC). Here, we sought to determine if high levels of the ADAM12 protein and/or messenger RNA (mRNA) are associated with clinical variables in HGSOC. We show that high protein levels of ADAM12 in banked preoperative sera are associated with shorter progression-free and overall survival. Tumor levels of ADAM12 mRNA were also associated with shorter progression-free and overall survival as well as with lymphatic and vascular invasion, and residual tumor volume following cytoreductive surgery. The majority of genes co-expressed with ADAM12 in HGSOC were transforming growth factor (TGF)β signaling targets that function in collagen remodeling and cell-matrix adhesion. In tumor sections, the ADAM12 protein and mRNA were expressed in epithelial cancer cells and surrounding stromal cells. In vitro data showed that ADAM12 mRNA levels can be increased by TGFβ signaling and direct contact between epithelial and stromal cells. High tumor levels of ADAM12 mRNA were characteristic of the mesenchymal/desmoplastic molecular subtype of HGSOC, which is known to have the poorest prognosis. Thus, ADAM12 may be a useful biomarker of aggressive ovarian cancer for which standard treatment is not effective. PMID:25926422

  17. Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

    PubMed

    Mignogna, Chiara; Staropoli, Nicoletta; Botta, Cirino; De Marco, Carmela; Rizzuto, Antonia; Morelli, Michele; Di Cello, Annalisa; Franco, Renato; Camastra, Caterina; Presta, Ivan; Malara, Natalia; Salvino, Angela; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Barni, Tullio; Donato, Giuseppe; Di Vito, Anna

    2016-01-01

    High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment. PMID:27209210

  18. Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas

    PubMed Central

    SORBE, BENGT

    2016-01-01

    The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non-endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I–IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors. PMID:26998163

  19. Should all patients with serous and clear cell endometrial carcinoma receive adjuvant chemotherapy?

    PubMed

    Boren, Todd P; Miller, David S

    2010-11-01

    Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent two rare subtypes that have an increased risk of recurrence and worse overall survival compared with the more common endometrioid endometrial cancers. Meaningful data in the form of prospective randomized trials is lacking for both advanced and early-stage UPSC and UCCC. Data extrapolated from prospective trials in advanced endometrioid endometrial cancer and retrospective trials on early-stage UPSC suggest that adjuvant platinum and taxane-based chemotherapy may provide a survival benefit for these patients. Future trials specifically examining UPSC and UCCC are needed to elucidate the optimal treatment regimen for these patients. Given the current data, the option of chemotherapy should be considered in treatment-planning discussions for all patients with UPSC and UCCC. PMID:21118038

  20. Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells

    PubMed Central

    Kashima, Hiroyasu; Yamada, Yasushi; Kobara, Hisanori; Asaka, Ryoichi; Ando, Hirofumi; Higuchi, Shotaro; Ida, Koichi; Mvunta, David Hamisi; Shiozawa, Tanri

    2016-01-01

    Purpose Lipocalin 2 (LCN2) is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear. Methods The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV) irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively. Results LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05). Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt) was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing. Conclusions These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells. PMID:27168162

  1. Marked heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma.

    PubMed

    Buza, Natalia; Hui, Pei

    2013-12-01

    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. PMID:24123408

  2. Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes.

    PubMed

    Hussein, Yaser R; Ducie, Jennifer A; Arnold, Angela G; Kauff, Noah D; Vargas-Alvarez, Hebert A; Sala, Evis; Levine, Douglas A; Soslow, Robert A

    2016-03-01

    Characteristic histopathologic features have been described in high-grade serous carcinoma associated with BRCA abnormalities (HGSC-BRCA), which are known to have relatively favorable clinical outcomes. The aim of this study was to evaluate the clinical significance of invasion patterns in metastatic HGSC-BRCA cases. Of the 37 cases of advanced-stage HGSC with known BRCA1 or BRCA2 germline mutation retrieved from our institutional files, 23 patients had a germline mutation of BRCA1 and 14 had a BRCA2 mutation. The pattern of invasion at metastatic sites was recorded and classified as a pushing pattern (either predominantly or exclusively), an exclusively micropapillary infiltrative pattern, or an infiltrative pattern composed of papillae, micropapillae, glands, and nests (mixed infiltrative pattern). Histologic evaluation of metastases was performed without knowledge of genotype or clinical outcome. Clinical data were abstracted from medical records. Median age was 56 years (range, 31 to 73 y). All patients presented at stage IIIC or IV and underwent complete surgical staging followed by chemotherapy. All 37 HGSC-BRCA cases showed either pushing pattern metastases (30; 81%) or infiltrative micropapillary metastases (7; 19%). No HGSC-BRCA case exhibited metastases composed solely of mixed infiltrative patterns. Among the 7 infiltrative micropapillary cases, 6 had a BRCA1 germline mutation versus 1 with a BRCA2 mutation. The median time of follow-up was 26 months (range, 13 to 49 mo). All 7 patients with infiltrative micropapillary metastases either experienced recurrence or died of disease (5 recurrences and 2 deaths), which was significantly worse than what was seen in patients with predominantly pushing pattern metastases, of whom 16 of 30 (53%) experienced recurrence (n=14) or died of disease (n=2) (P=0.03). In conclusion, the recognition of different invasion patterns of metastatic extrauterine HGSC-BRCA has prognostic implications. The infiltrative

  3. Clinical Significance of Positive Pelvic Washings in Uterine Papillary Serous Carcinoma Confined to an Endometrial Polyp.

    PubMed

    Hanley, Krisztina Z; Fadare, Oluwole; Fisher, Kevin E; Atkins, Kristen A; Mosunjac, Marina B

    2016-05-01

    Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC. PMID:26535985

  4. Near-infrared spectroscopic applications for diagnosis of endometrial carcinoma.

    PubMed

    Xiang, Yuhong; Xu, Ke; Zhang, Zhuoyong; Dai, Yinmei; Harrington, Peter de B

    2010-01-01

    NIR spectra of 77 endometrium sections (malignant, hyperplasia, and normal samples) are collected. Partial least squares discriminant analysis (PLS-DA) and fuzzy rule-building expert systems (FuRES) are used for classification based on the NIR spectral data. The classification ability of two classifiers is evaluated by using ten bootstraps and five Latin partitions. The results indicate that the classification ability of FuRES is better than that of PLS-DA. The sensitivity, specificity, and accuracy obtained from FuRES for malignant endometrium diagnosis are 90.0±0.7, 95.0±0.8, and 93.1±0.8%, respectively. The results demonstrate that NIR spectroscopy combined with the FuRES technique is promising for the classification of endometrial specimens and for practical diagnostic applications. PMID:21198206

  5. Near-infrared spectroscopic applications for diagnosis of endometrial carcinoma

    NASA Astrophysics Data System (ADS)

    Xiang, Yuhong; Xu, Ke; Zhang, Zhuoyong; Dai, Yinmei; Harrington, Peter De B.

    2010-11-01

    NIR spectra of 77 endometrium sections (malignant, hyperplasia, and normal samples) are collected. Partial least squares discriminant analysis (PLS-DA) and fuzzy rule-building expert systems (FuRES) are used for classification based on the NIR spectral data. The classification ability of two classifiers is evaluated by using ten bootstraps and five Latin partitions. The results indicate that the classification ability of FuRES is better than that of PLS-DA. The sensitivity, specificity, and accuracy obtained from FuRES for malignant endometrium diagnosis are 90.0+/-0.7, 95.0+/-0.8, and 93.1+/-0.8%, respectively. The results demonstrate that NIR spectroscopy combined with the FuRES technique is promising for the classification of endometrial specimens and for practical diagnostic applications.

  6. Unusual Mismatch Repair Immunohistochemical Patterns in Endometrial Carcinoma.

    PubMed

    Watkins, Jaclyn C; Nucci, Marisa R; Ritterhouse, Lauren L; Howitt, Brooke E; Sholl, Lynette M

    2016-07-01

    Universal screening for Lynch syndrome through mismatch repair (MMR) immunohistochemistry (IHC) on tumor samples has brought to light several heterogenous MMR staining patterns. At our institution, a prospective study of universal Lynch syndrome screening using MMR IHC on 125 endometrial cancers (EC) led to the identification of subclonal loss of MMR protein expression within the tumor (n=9). We also interrogated the MMR staining patterns in MMR-deficient EC with concurrent endometrial intraepithelial neoplasia (EIN; n=14) and all mixed-type ECs (n=14) to look for concordant or discordant profiles between the various components. MLH1 promoter methylation and microsatellite instability testing was performed on discordant subclones. Abrupt and complete subclonal loss of MMR expression was identified in 9 cases (7.2%; 7 subclonal MLH1/PMS2 loss, 1 subclonal loss of MLH1 and complete loss of PMS2, and 1 subclonal MSH6 loss). All subclonal MLH1 losses were associated with epigenetic silencing. In cases with concomitant EIN (n=14), 7 cases showed concordant MMR IHC between EC and EIN, and 4 cases showed MMR protein loss confined to the EC. The remaining 3 cases demonstrated subclonal staining in the EIN. In mixed tumors (n=14), subclonal or total MMR IHC deficiency was confined to endometrioid components. In summary, discrete subclonal loss of MMR protein expression occurs in up to 7.2% of EC and, in our experience, only in endometrioid components. Importantly, subclonal MLH1 MMR defects appear to be a biological phenomenon that can be explained by methylation and somatic events, without evidence of underlying germline alterations. PMID:27186853

  7. Inverse p16 and p63 expression in small cell carcinoma and high-grade urothelial cell carcinoma of the urinary bladder.

    PubMed

    Buza, Natalia; Cohen, Paul J; Pei Hui; Parkash, Vinita

    2010-04-01

    Small cell carcinoma (SmCC) of the urinary bladder is a rare, highly aggressive neoplasm. The diagnosis is usually made on morphologic grounds, with the help of immunohistochemistry to document neuroendocrine differentiation. However, neuroendocrine markers generally have low sensitivity, ranging between 30-70%. Recent studies have reported p16 over-expression in SmCC of the lung, suggesting that p16 immunohistochemistry may be useful in the diagnosis of bladder SmCC. This is the first study to analyze the usefulness of p16 in the distinction of small cell and high grade urothelial cell carcinoma (HG-UCC). Fourteen cases of SmCCs and sixteen cases of HG-UCC of the bladder were stained with p16, p63, cytokeratin 20 (CK20), cytokeratin 7 (CK7), chromogranin (Chr), synaptophysin (Syn), and CD56. P16 expression was significantly higher in SmCCs (92.8%) when compared to HG-UCCs (43.7%). P63 and CK20, on the other hand, were positive in the majority of HG-UCCs (81.3% and 50%, respectively), while only 14.3% of SmCCs showed focal immunoreactivity with CK20. The sensitivity of the traditional neuroendocrine markers was low, ranging between 28.6% (Chr) and 71.4% (CD56) in SmCCs. P16 positivity in the absence of p63 and CK20 is highly characteristic of SmCC, while p63 and CK20 positivity with or without p16 expression is typical of HG-UCC. PMID:20164052

  8. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer

    PubMed Central

    El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D

    2012-01-01

    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. PMID:22149431

  9. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer

    PubMed Central

    Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D

    2014-01-01

    Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC. PMID:24328598

  10. Pelvic recurrence of stage 1a well-differentiated endometrial carcinoma after 13 years: A case report

    PubMed Central

    Kim, Annie; Nguyen, Long; Kalir, Tamara; Chuang, Linus

    2016-01-01

    A great majority of endometrial carcinoma recurrences are observed in high-risk patients and within the first 3 years of treatment. The relapse of endometrial carcinoma occurring more than 10 years after initial treatment has rarely been described. Initially diagnosed and treated for International Federation of Gynecology and Obstetrics (FIGO) stage 1a, grade 1 adenocarcinoma, our patient presented 13 years later with an isolated pelvic recurrence, demonstrating, to our knowledge, the longest disease-free interval with recurrence in the pelvis reported in literature. After surgical resection, the patient is being considered for enrollment in a clinical trial. Despite favorable prognostic features, it is possible to observe the recurrence of endometrial carcinoma even 5 years after surveillance and remission. Successful salvage therapies are available but may depend upon early diagnosis. PMID:27026780

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

    PubMed

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

    2010-04-01

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

  12. The diagnostic value of the ThinPrep pap test in endometrial carcinoma: a prospective study with histological follow-up.

    PubMed

    Zhou, Jianhong; Tomashefski, Joseph F; Sawady, Joram; Ferrer, Hector; Khiyami, Amer

    2013-05-01

    Case-control studies have demonstrated that the ThinPrep Pap test may provide improved detection of endometrial carcinoma. The purpose of this study is to prospectively examine the diagnostic potential of the ThinPrep Pap test in the detection of endometrial carcinoma. ThinPrep Pap test slides were collected from high-risk patient groups. Pap-stained slides were reviewed and the cytological diagnosis was rendered independently by investigators. Each case was assigned to one of the four diagnostic categories: within normal limit (WNL); atypical glandular cells (AGC); atypical endometrial cells (AEC); or adenocarcinoma, probably endometrial origin. After cytological diagnosis was made, the histological follow-up diagnosis was obtained through the laboratory information system and the cyto-histological correlation was analyzed. Of 106 patients identified, 60 had histological follow-up. For all eight cases interpreted by cytology as positive, endometrial carcinoma was confirmed histologically. Among 25 patients with normal endometrial cells present, histological follow-up showed benign endometrium. Among 17 cases interpreted cytologically as AEC, 14 cases (82.4%) had benign histological follow-up and 3 cases (17.6%) had endometrial carcinoma. All 11 cases (100%) classified as AGC had benign histological follow-up. The sensitivity and specificity of detecting endometrial malignancy were 72.7% and 100%, respectively. The positive predictive value was 100%. In this prospective study, we demonstrated that the Thin Prep Pap test had a reasonably high sensitivity and/or specificity in detecting endometrial carcinoma. PMID:22351503

  13. Inhibitory effects of bark extracts from Ulmus laevis on endometrial carcinoma: an in-vitro study.

    PubMed

    Paschke, Daniel; Abarzua, Sibylle; Schlichting, André; Richter, Dagmar-Ulrike; Leinweber, Peter; Briese, Volker

    2009-04-01

    Anti-inflammatory effects of elm tree have been shown in several studies. Besides this, protective effects of components of elm bark on damaged tissue have also been described. This study was carried out to investigate the antitumour potential of an ethanolic extract isolated from Ulmus laevis in the hormone-dependent endometrial carcinoma cell line RL95-2. A range of 2.5-500 microg/ml of elm bark extract was used as standard concentrations. The molecular-chemical composition of the bark extract was analysed by pyrolysis-field ionization mass spectrometry. The influence of the bark extracts was determined on cell vitality [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test], cell proliferation (5-bromo-2-deoxyuridine test) and cytotoxicity (lactate dehydrogenase test) in the human endometrial carcinoma cell line RL 95-2. By pyrolysis-field ionization mass spectrometry, the main substance classes of the extract as a composition of sterols/triterpenes, free fatty acids and a group of phenols, lignin monomers and flavonoids was identified. Our study showed a significant inhibition of cell vitality and proliferation measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test up to 5 microg/ml extract and up to 100 microg/ml according to the 5-bromo-2-deoxyuridine test. Concentrations of 500 microg/ml induced a significant inhibition of cell vitality up to 80% and cell proliferation up to 81.5%. A significant cytotoxity was not observed. The results lead to the assumption that the bark extract from Ulmus laevis has antiproliferation and anticancer potential in hormone-dependent endometrial carcinoma cells. PMID:19337064

  14. Adjuvant Pelvic Radiotherapy vs. Sequential Chemoradiotherapy for High-Risk Stage I-II Endometrial Carcinoma

    PubMed Central

    El-Hadaad, Hend Ahmed; Wahba, Hanan Ahmed; Gamal, Anas Mohamed; Dawod, Tamer

    2012-01-01

    Objective To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival (OAS), and progression free survival (PFS); to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma Methods Medical records were reviewed to identify high-risk stage I-II endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone (arm I) (57 patients) or with sequential carboplatin (AUC5-6) and paclitaxel (135−175 mg/m2) with radiotherapy (arm II) (51 patients). Radiotherapy was performed through the four-field box technique at doses of 45−50 Gy (1.8 Gy/day × 5 days/week). Results The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm I and arm II, respectively, without febrile neutropenia. All patients experienced hair loss. Chemoradiotherapy arm was associated with a lower incidence rate of relapse (9.8% vs. 22.7%). After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy (P=0.02 and 0.03, respectively). In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%. Conclusions Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage I-II endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage I-II endometrial carcinoma. PMID:23691474

  15. Transvaginal Ultrasound for Endometrial Carcinoma Screening – Current Evidence-based Data

    PubMed Central

    Steiner, E.; Juhasz-Bösz, I.; Emons, G.; Kölbl, H.; Kimmig, R.; Mallmann, P.

    2012-01-01

    The value of transvaginal ultrasound in gynaecological examinations is beyond dispute. But it is of particular forensic importance that the validity of this type of imaging with regard to the reliable detection of early-stage malignancy is properly understood. Vaginal ultrasound screening in asymptomatic patients for the early detection of endometrial carcinoma is not useful from a medical point of view, nor is it cost-efficient. However, even though the validity of transvaginal ultrasound for screening has currently not been proven, the method should still be an integral part of gynaecological examinations. PMID:25278620

  16. Effect of cyclin-dependent kinase 7 silencing on cisplatin sensitivity in endometrial carcinoma cells

    PubMed Central

    LIU, WEN-XIN; LIU, XIANG-YU; YU, HU; CHEN, YING; HAO, QUAN

    2015-01-01

    The aim of the present study was to determine the effect of cyclin-dependent kinase 7 (CDK7) silencing on the sensitivity of the HEC-1-A endometrial carcinoma cell line to cisplatin [cis-dichlorodiammineplatinum (II), or DDP]. Four CDK7 siRNA fragments were designed and synthesized based on the gene sequence of CDK7 and transfected into HEC-1-A cells. The RNA interference of the fragments was confirmed by semi-quantitative polymerase chain reaction (PCR) and western blot analyses. The CDK7-423 siRNA fragment exhibited the most marked silencing of CDK-7 (>70%), and was chosen for the subsequent experiments in HEC-1-A endometrial carcinoma cells. The sensitivity of the cells to a chemotherapeutic agent (cisplatin) was determined before and after transfection of the siRNA, using a MTT cytotoxicity assay, flow cytometry and Hoechst/propidium iodide (PI) double-staining immunofluorescence microscopy. The results of the MTT cytotoxicity assay showed that the half maximal inhibitory concentration of cisplatin was reduced from 45.12 μg/ml to 3.200 μg/ml following the inhibition of CDK7 expression levels, indicating a significantly increased cytotoxicity in the treated cells (P<0.05). The flow cytometry analysis showed that the mean rate of apoptosis in the CDK7 low-expression group was 37.57%, which was significantly higher than the rate in the parental cells (11.66%) (P<0.05). Hoechst/PI co-immunofluorescence microscopy revealed that the number of apoptotic bodies in the CDK7 low-expression HEC-1-A cells was significantly increased as compared with the parental cells. Downregulation of CDK7 expression levels in HEC-1-A endometrial carcinoma cells via the transfection of CDK7 siRNA may significantly enhance cancer cell sensitivity to cisplatin chemotherapy and increasing apoptosis. CDK7 is a novel promising treatment for endometrial carcinoma that requires further in-depth study. PMID:25411854

  17. CDKN2D-WDFY2 Is a Cancer-Specific Fusion Gene Recurrent in High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Rajapakshe, Kimal; Hawkins, Shannon M.; Matzuk, Martin M.; Milosavljevic, Aleksandar; Yen, Laising

    2014-01-01

    Ovarian cancer is the fifth leading cause of cancer death in women. Almost 70% of ovarian cancer deaths are due to the high-grade serous subtype, which is typically detected only after it has metastasized. Characterization of high-grade serous cancer is further complicated by the significant heterogeneity and genome instability displayed by this cancer. Other than mutations in TP53, which is common to many cancers, highly recurrent recombinant events specific to this cancer have yet to be identified. Using high-throughput transcriptome sequencing of seven patient samples combined with experimental validation at DNA, RNA and protein levels, we identified a cancer-specific and inter-chromosomal fusion gene CDKN2D-WDFY2 that occurs at a frequency of 20% among sixty high-grade serous cancer samples but is absent in non-cancerous ovary and fallopian tube samples. This is the most frequent recombinant event identified so far in high-grade serous cancer implying a major cellular lineage in this highly heterogeneous cancer. In addition, the same fusion transcript was also detected in OV-90, an established high-grade serous type cell line. The genomic breakpoint was identified in intron 1 of CDKN2D and intron 2 of WDFY2 in patient tumor, providing direct evidence that this is a fusion gene. The parental gene, CDKN2D, is a cell-cycle modulator that is also involved in DNA repair, while WDFY2 is known to modulate AKT interactions with its substrates. Transfection of cloned fusion construct led to loss of wildtype CDKN2D and wildtype WDFY2 protein expression, and a gain of a short WDFY2 protein isoform that is presumably under the control of the CDKN2D promoter. The expression of short WDFY2 protein in transfected cells appears to alter the PI3K/AKT pathway that is known to play a role in oncogenesis. CDKN2D-WDFY2 fusion could be an important molecular signature for understanding and classifying sub-lineages among heterogeneous high-grade serous ovarian carcinomas. PMID

  18. Endometrial cancers occurring 10 or more years after pelvic irradiation for carcinoma

    SciTech Connect

    Rodriguez, J.; Hart, W.R.

    1982-01-01

    Fifteen patients who developed cancer of the endometrium 10 or more years after pelvic irradiation for carcinoma were selected for study from a group of 64 cases of postirradiation malignant pelvic tumors diagnosed during a 48-year span. The average interval between radiotherapy and diagnosis of the subsequent endometrial cancer was 17.2 years. Irradiation initially had been done for squamous cell carcinoma of the cervix in 13 cases (87%) and for ovarian tumors in two instances. Almost all patients had received megavoltage external radiation combined with radium implants. Two-thirds of the tumors were adenocarcinomas and one-third were carcinosarcomas (either homologous or heterologous). Although the risk of second primary malignant tumors following therapeutic irradiation for pelvic tumors probably is very low, the emergence of new genital tract cancers in long-term survivors must be anticipated, regardless of whether the postirradiation cancers are spontaneous or radiation-induced.

  19. Validation of endogenous control reference genes for normalizing gene expression studies in endometrial carcinoma.

    PubMed

    Ayakannu, Thangesweran; Taylor, Anthony H; Willets, Jonathon M; Brown, Laurence; Lambert, David G; McDonald, John; Davies, Quentin; Moss, Esther L; Konje, Justin C

    2015-09-01

    Real-time quantitative RT-PCR (qRT-PCR) is a powerful technique used for the relative quantification of target genes, using reference (housekeeping) genes for normalization to ensure the generation of accurate and robust data. A systematic examination of the suitability of endogenous reference genes for gene expression studies in endometrial cancer tissues is absent. The aims of this study were therefore to identify and evaluate from the thirty-two possible reference genes from a TaqMan(®) array panel their suitability as an internal control gene. The mathematical software packages geNorm qBasePLUS identified Pumilio homolog 1 (Drosophila) (PUM1), ubiquitin C (UBC), phosphoglycerate kinase (PGK1), mitochondrial ribosomal protein L19 (MRPL19) and peptidylpropyl isomerase A (cyclophilin A) (PPIA) as the best reference gene combination, whilst NormFinder identified MRPL19 as the best single reference gene, with importin 8 (IPO8) and PPIA being the best combination of two reference genes. BestKeeper ranked MRPL19 as the most stably expressed gene. In addition, the study was validated by examining the relative expression of a test gene, which encodes the cannabinoid receptor 1 (CB1). A significant difference in CB1 mRNA expression between malignant and normal endometrium using MRPL19, PPIA, and IP08 in combination was observed. The use of MRPL19, IPO8 and PPIA was identified as the best reference gene combination for the normalization of gene expression levels in endometrial carcinoma. This study demonstrates that the arbitrary selection of endogenous control reference genes for normalization in qRT-PCR studies of endometrial carcinoma, without validation, risks the production of inaccurate data and should therefore be discouraged. PMID:26124453

  20. Primary Endometrial Squamous Cell Carcinoma In Situ: Report of a rare disease.

    PubMed

    Jetley, Sujata; Jairajpuri, Zeeba S; Hassan, Mohammad J; Madaan, Garima; Jain, Reena

    2015-11-01

    Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year's duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up. PMID:26629388

  1. Stage II endometrial carcinoma. Results and complications of a combined radiotherapeutic-surgical approach

    SciTech Connect

    Larson, D.M.; Copeland, L.J.; Gallager, H.S.; Kong, J.P.; Wharton, J.T.; Stringer, C.A.

    1988-04-15

    Since one third of the patients with Stage II endometrial carcinoma have occult extrauterine pelvic metastases at diagnosis, adequate treatment must include the pelvic lymph nodes and parametria. Eighty-three patients with Stage II endometrial carcinoma were treated between January 1964 and December 1983. Sixty-nine patients (83%) received combined whole-pelvic irradiation and surgery, five (6%) had surgery alone and nine (11%) had radiotherapy alone. Five-year actuarial survival rates were 67%, 60%, and 38%, respectively. No pelvic recurrence occurred in the 69 patients who received the combined therapy, and there was no vaginal recurrence in the 80 patients treated with intracavity radium. There was a significantly lower incidence of pelvic lymph node metastases (P = 0.03) in patients treated with preoperative irradiation. The median time to recurrence was 17 months, with 67% of the recurrences diagnosed before 2 years, and 88% within 5 years. Ten patients (12%) incurred severe complications and three died as a result. Whole-pelvic irradiation, intracavity radium, and hysterectomy are effective treatment for occult pelvic and vaginal disease.

  2. Recurrent Stage I endometrial carcinoma: results of treatment and prognostic factors

    SciTech Connect

    Mandell, L.R.; Nori, D.; Hilaris, B.

    1985-06-01

    Recurrences of clinical Stage I endometrial carcinoma after initial treatment are rare. They are nonetheless a serious complication, uniformly associated with poor outcome. Between 1969-1980, 20 patients with clinical Stage I endometrial carcinoma were treated for recurrent tumor at the time of first relapse. Nonpapillary adenocarcinoma represented 70% of the primary tumors and papillary adenocarcinoma, 30%. The median time to recurrence after completion of primary treatment was 9.5 mo. The vagina was the site of relapse in 65% of patients, the abdomen in 20%, the pelvis in 10% and the lung in 5%. Ninety-five percent of recurrences were treated with curative intent. Complications were seen in three patients, small bowel obstruction (2 pts) and vaginal vault necrosis (1 pt); however, these patients responded effectively to conservative treatment. The review suggests that: (1) Histology and site of relapse are important prognosticators of treatment outcome; (2) Long term survival may be achieved in vaginal recurrences with aggressive local treatment; and (3) There may be a role for multimodality ovarian type treatment in overall management of recurrent papillary adenocarcinoma, a cell type that appears to exhibit a tendency towards extrapelvic spread refractory to definitive loco-regional treatment.

  3. Utility of ovarian biopsy in pancreatic metastasis of high-grade serous ovarian carcinoma: A case report

    PubMed Central

    NAKAMURA, KOHEI; NAKAYAMA, KENTARO; ISHIKAWA, MASAKO; ISHIKAWA, NORIYOSHI; NAGASE, MAMIKO; KATAGIRI, HIROSHI; ISHIBASHI, TOMOKA; SATO, EMI; IIDA, KOHJI; SULTANA, RAZIA; KYO, SATORU

    2016-01-01

    It is very rare that ovarian carcinoma metastasizes to the pancreas, and pathological diagnosis is required to confirm the primary site. The present study reported a 73-year-old woman with serous carcinoma of the ovary that metastasized to the tail of the pancreas. Metastasis was confirmed by pathological and immunohistochemical examination of a biopsy of the ovarian tumor, an endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreatic tumor and computerized tomography-guided paraaortic lymph node biopsy. A biopsy of the ovarian tumor is useful to make a precise diagnosis and to determine proper treatment when ovarian and pancreatic tumors are identified at the same time and the primary neoplasm is uncertain. PMID:27330762

  4. Accumulated Metabolites of Hydroxybutyric Acid Serve as Diagnostic and Prognostic Biomarkers of Ovarian High-Grade Serous Carcinomas.

    PubMed

    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; Darb-Esfahani, Silvia; Braicu, Elena Ioana

    2016-02-15

    Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but it 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 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

  5. Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas

    PubMed Central

    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

    2016-01-01

    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

  6. Screening for Endometrial Cancer

    PubMed Central

    Nisker, Jeffrey A.

    1983-01-01

    Although population screening for cervical neoplasia is widely practiced, screening for endometrial neoplasia has only recently been considered. Before development of endometrial carcinoma, the endometrium undergoes progressive neoplastic alterations in a parallel fashion to the premalignant precursors of cervical carcinoma. Screening for endometrial carcinoma may be particularly appropriate because of the existence of a well defined, easily identifiable high risk group and tissue sampling techniques that are accurate, easy to perform, inexpensive, and well tolerated. Women at increased risk of endometrial carcinoma include: obese postmenopausal women, women on postmenopausal estrogen replacement therapy, premenopausal women with a history of anovulatory cycles (including women with polycystic ovarian disease) and women with hepatic cirrhosis. Using endometrial aspiration devices, screening for endometrial hyperplasia and carcinoma may be performed by any physician familiar with intrauterine contraceptive device insertion in the office. The impact of such routine screening of high risk women will be determined only after large screening studies have been accomplished. PMID:21283374

  7. Analysis of residual disease following preoperative radiotherapy versus initial surgery in endometrial carcinoma

    SciTech Connect

    Chung, C.K.; Stryker, J.A.; Nahhas, W.A.; Cunningham, D.E.; Mortel, R.

    1982-02-01

    A clinicopathologic study of residual disease following pre-operative radiotherapy (RT) in 67 patients and initial surgery in 40 patients with early invasive endometrial carcinoma is presented. In 10%, extrauterine spread was found at operation. In 10% of patients, the histologic type, and in 19% the grade of tumor, differed between the curettage and hysterectomy specimens. Pre-op RT altered the depth of myometrial invasion and frequency of vascular invasion, but there was no evidence that irradiation itself affected the histologic type or grade of tumor. The patients with residual tumor after pre-op RT had significantly more cancer-related deaths than those without residual disease. The high risk factors were deep myometrial invasion and residual disease outside the uterus. Vascular invasion did not affect the prognosis in this series. The importance of surgical-pathologic staging by initial surgery is discussed.

  8. Markers of T Cell Infiltration and Function Associate with Favorable Outcome in Vascularized High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Townsend, Katelin N.; Spowart, Jaeline E.; Huwait, Hassan; Eshragh, Sima; West, Nathan R.; Elrick, Mary A.; Kalloger, Steve E.; Anglesio, Michael; Watson, Peter H.; Huntsman, David G.; Lum, Julian J.

    2013-01-01

    Background When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL) could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. Methodology and Principal Findings In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3)) and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1)) correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049–5.106); p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF) expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097–5.799); p = 0.0294]. Significance Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions. PMID:24376535

  9. Robot-Assisted Laparoscopic Bladder Diverticulectomy and Ureteral Re-Implantation for a Diverticulum Containing High Grade Transitional Cell Carcinoma

    PubMed Central

    Elands, Sophie; Vasdev, Nikhil; Tay, Andrea; Adshead, James M.

    2015-01-01

    We present a case of an 84-year-old man presenting with painless visible hematuria. Further investigation revealed a primary G3pT1 transitional cell carcinoma confined to a bladder diverticulum. In view of bladder-sparing therapy, he underwent a robot-assisted laparoscopic bladder diverticulectomy with ureteral re-implantation. This report demonstrates a minimally invasive approach offering radical treatment without having to recur to partial or radical cystectomy. We discuss the operative steps, the significance of this case with a review of the literature, and the future potential this may represent for the treatment of tumor-containing bladder diverticula. PMID:26889127

  10. Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas.

    PubMed

    Karnezis, Anthony N; Hoang, Lien N; Coatham, Mackenzie; Ravn, Sarah; Almadani, Noorah; Tessier-Cloutier, Basile; Irving, Julie; Meng, Bo; Li, Xiaodong; Chow, Christine; McAlpine, Jessica; Kuo, Kuan-Ting; Mao, Tsui-Lien; Djordjevic, Bojana; Soslow, Robert A; Huntsman, David G; Blake Gilks, C; Köbel, Martin; Lee, Cheng-Han

    2016-03-01

    Dedifferentiated endometrial carcinoma is an aggressive type of endometrial cancer that contains a mix of low-grade endometrioid and undifferentiated carcinoma components. We performed targeted sequencing of eight dedifferentiated carcinomas and identified somatic frameshift/nonsense mutations in SMARCA4, a core ATPase of the switch/sucrose non-fermenting (SWI/SNF) complex, in the undifferentiated components of four tumors. Immunohistochemical analysis confirmed the loss of SMARCA4 in the undifferentiated component of these four SMARCA4-mutated cases, whereas the corresponding low-grade endometrioid component showed retained SMARCA4 expression. An expanded survey of other members of the SWI/SNF complex showed SMARCB1 loss in the undifferentiated component of two SMARCA4-intact tumors, and all SMARCA4- or SMARCB1-deficient tumors showed concomitant loss of expression of SMARCA2. We subsequently examined the expression of SMARCA2, SMARCA4, and SMARCB1 in an additional set of 22 centrally reviewed dedifferentiated carcinomas and 31 grade 3 endometrioid carcinomas. Combining the results from the index and the expansion set, 15 of 30 (50%) of the dedifferentiated carcinomas examined showed either concurrent SMARCA4 and SMARCA2 loss (37%) or concurrent SMARCB1 and SMARCA2 loss (13%) in the undifferentiated component. The loss of SMARCA4 or SMARCB1 was mutually exclusive. All 31 grade 3 endometrioid carcinomas showed intact expression of these core SWI/SNF proteins. The majority (73%) of the SMARCA4/SMARCA2-deficient and half of SMARCB1/SMARCA2-deficient undifferentiated component developed in a mismatch repair-deficient molecular context. The observed spatial association between SWI/SNF protein loss and histologic dedifferentiation suggests that inactivation of these core SWI/SNF proteins may contribute to the development of dedifferentiated endometrial carcinoma. PMID:26743474

  11. Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2016-07-04

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  12. FGFR3b Extracellular Loop Mutation Lacks Tumorigenicity In Vivo but Collaborates with p53/pRB Deficiency to Induce High-grade Papillary Urothelial Carcinoma

    PubMed Central

    Zhou, Haiping; He, Feng; Mendelsohn, Cathy L.; Tang, Moon-shong; Huang, Chuanshu; Wu, Xue-Ru

    2016-01-01

    Missense mutations of fibroblast growth factor receptor 3 (FGFR3) occur in up to 80% of low-grade papillary urothelial carcinoma of the bladder (LGP-UCB) suggesting that these mutations are tumor drivers, although direct experimental evidence is lacking. Here we show that forced expression of FGFR3b-S249C, the most prevalent FGFR3 mutation in human LGP-UCB, in cultured urothelial cells resulted in slightly reduced surface translocation than wild-type FGFR3b, but nearly twice as much proliferation. When we expressed a mouse equivalent of this mutant (FGFR3b-S243C) in urothelia of adult transgenic mice in a tissue-specific and inducible manner, we observed significant activation of AKT and MAPK pathways. This was, however, not accompanied by urothelial proliferation or tumorigenesis over 12 months, due to compensatory tumor barriers in p16-pRB and p19-p53-p21 axes. Indeed, expressing FGFR3b-S249C in cultured human urothelial cells expressing SV40T, which functionally inactivates pRB/p53, markedly accelerated proliferation and cell-cycle progression. Furthermore, expressing FGFR3b-S243C in transgenic mouse urothelium expressing SV40T converted carcinoma-in-situ to high-grade papillary urothelial carcinoma. Together, our study provides new experimental evidence indicating that the FGFR3 mutations have very limited urothelial tumorigenicity and that these mutations must collaborate with other genetic events to drive urothelial tumorigenesis. PMID:27157475

  13. FGFR3b Extracellular Loop Mutation Lacks Tumorigenicity In Vivo but Collaborates with p53/pRB Deficiency to Induce High-grade Papillary Urothelial Carcinoma.

    PubMed

    Zhou, Haiping; He, Feng; Mendelsohn, Cathy L; Tang, Moon-Shong; Huang, Chuanshu; Wu, Xue-Ru

    2016-01-01

    Missense mutations of fibroblast growth factor receptor 3 (FGFR3) occur in up to 80% of low-grade papillary urothelial carcinoma of the bladder (LGP-UCB) suggesting that these mutations are tumor drivers, although direct experimental evidence is lacking. Here we show that forced expression of FGFR3b-S249C, the most prevalent FGFR3 mutation in human LGP-UCB, in cultured urothelial cells resulted in slightly reduced surface translocation than wild-type FGFR3b, but nearly twice as much proliferation. When we expressed a mouse equivalent of this mutant (FGFR3b-S243C) in urothelia of adult transgenic mice in a tissue-specific and inducible manner, we observed significant activation of AKT and MAPK pathways. This was, however, not accompanied by urothelial proliferation or tumorigenesis over 12 months, due to compensatory tumor barriers in p16-pRB and p19-p53-p21 axes. Indeed, expressing FGFR3b-S249C in cultured human urothelial cells expressing SV40T, which functionally inactivates pRB/p53, markedly accelerated proliferation and cell-cycle progression. Furthermore, expressing FGFR3b-S243C in transgenic mouse urothelium expressing SV40T converted carcinoma-in-situ to high-grade papillary urothelial carcinoma. Together, our study provides new experimental evidence indicating that the FGFR3 mutations have very limited urothelial tumorigenicity and that these mutations must collaborate with other genetic events to drive urothelial tumorigenesis. PMID:27157475

  14. Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2016-07-26

    Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma

  15. Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas.

    PubMed

    Schultheis, Anne M; Ng, Charlotte K Y; De Filippo, Maria R; Piscuoglio, Salvatore; Macedo, Gabriel S; Gatius, Sonia; Perez Mies, Belen; Soslow, Robert A; Lim, Raymond S; Viale, Agnes; Huberman, Kety H; Palacios, Jose C; Reis-Filho, Jorge S; Matias-Guiu, Xavier; Weigelt, Britta

    2016-06-01

    Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other. PMID:26832770

  16. Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-12-22

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  17. Cytoreduction and intraperitoneal heated chemotherapy for the treatment of endometrial carcinoma recurrent within the peritoneal cavity.

    PubMed

    Helm, C W; Toler, C R; Martin, R S; Gordinier, M E; Parker, L P; Metzinger, D S; Edwards, R P

    2007-01-01

    Our experience with hyperthermic intraperitoneal chemotherapy (IPHC) in conjunction with surgical resection for endometrial cancer recurrent within the abdominal cavity was reviewed. Eligible patients underwent exploratory laparotomy with the aim of resecting disease to < or =5 mm maximum dimension followed immediately by intraperitoneal perfusion of cisplatin (100 mg/m(2)) heated to 41-43 degrees C (105.8-109.4 degrees F) for 1.5 h. Data for analysis was extracted from retrospective chart review. Five patients underwent surgery and IPHC between September 2002 and January 2005 for abdomino-pelvic recurrence. Original stage and histology were 1A papillary serous (1), 1C endometrioid with clear cell features (1), and 1B endometrioid (3). Mean age was 61 (41-75) years, mean prior laparotomies were 1.4 (1-2), and mean chemotherapy agent exposure was 1.6 (0-4). Mean time from initial treatment to surgery and IPHC was 47 (29-66) months. Mean length of surgery was 9.8 (7-11) h after which three patients had no residual disease and two had < or =5 mm disease. The mean duration of hospital stay was 12.6 (6-20) days. Postoperative surgical complications included wound infection with septicemia in one patient. Mean maximum postoperative serum creatinine was 1.02 (0.6-1.70) mg/dL. There was no ototoxicity or neuropathy and no perioperative mortality. No patients have been lost to follow-up. Two are living disease free at 28 and 32 m and two are living with disease at 12 and 36 m. One patient died at 3 m without evidence of cancer. Two patients who had no residual macroscopic disease at the end of surgery are alive at 32 and 36 m. The combination of IPHC with surgery for recurrent endometrial carcinoma is relatively well tolerated. The unexpectedly long survival seen in this cohort supports a phase II trial of IPHC with cisplatin for recurrent endometrial cancer. PMID:17291254

  18. MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas

    PubMed Central

    Gruosso, Tina; Garnier, Camille; Abelanet, Sophie; Kieffer, Yann; Lemesre, Vincent; Bellanger, Dorine; Bieche, Ivan; Marangoni, Elisabetta; Sastre-Garau, Xavier; Mieulet, Virginie; Mechta-Grigoriou, Fatima

    2015-01-01

    Ovarian cancer is a silent disease with a poor prognosis that urgently requires new therapeutic strategies. In low-grade ovarian tumours, mutations in the MAP3K BRAF gene constitutively activate the downstream kinase MEK. Here we demonstrate that an additional MAP3K, MAP3K8 (TPL-2/COT), accumulates in high-grade serous ovarian carcinomas (HGSCs) and is a potential prognostic marker for these tumours. By combining analyses on HGSC patient cohorts, ovarian cancer cells and patient-derived xenografts, we demonstrate that MAP3K8 controls cancer cell proliferation and migration by regulating key players in G1/S transition and adhesion dynamics. In addition, we show that the MEK pathway is the main pathway involved in mediating MAP3K8 function, and that MAP3K8 exhibits a reliable predictive value for the effectiveness of MEK inhibitor treatment. Our data highlight key roles for MAP3K8 in HGSC and indicate that MEK inhibitors could be a useful treatment strategy, in combination with conventional chemotherapy, for this disease. PMID:26456302

  19. Fifteen-Year Radiotherapy Outcomes of the Randomized PORTEC-1 Trial for Endometrial Carcinoma

    SciTech Connect

    Creutzberg, Carien L.; Nout, Remi A.; Lybeert, Marnix L.M.; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Mens, Jan-Willem M.; Lutgens, Ludy C.H.W.; Pras, Elisabeth; Poll-Franse, Lonneke V. van de; Putten, Wim L.J. van

    2011-11-15

    Purpose: To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers. Patients and Methods: The PORTEC trial (1990-1997) included 714 patients with Stage IC Grade 1-2 or Stage IB Grade 2-3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat. Results: 426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02). Conclusions: The 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC.

  20. Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma.

    PubMed

    Ohnishi, Koji; Yamaguchi, Munekage; Erdenebaatar, Chimeddulam; Saito, Fumitaka; Tashiro, Hironori; Katabuchi, Hidetaka; Takeya, Motohiro; Komohara, Yoshihiro

    2016-06-01

    Lymph node (LN) macrophages play critical roles in anti-tumor immunity, which develops via the activation of cytotoxic T cells (CTL) and NK cells. The present study aims to determine the prognostic significance of CD169(+) LN macrophages in patients with endometrial carcinoma (EC). The number of CD169(+) cells or the CD169(+) -to-CD68(+) macrophage ratio in regional LN (RLN), and the number of CD8(+) CTL or CD57(+) NK cells in tumor tissues were investigated by immunohistochemistry in paraffin-embedded tissue samples from 79 patients with EC. A high density of CD169(+) cells in the RLN of patients with EC was correlated with an early clinical stage or no LN metastasis. A high number of CD169(+) cells and a high CD169(+) -to-CD68(+) macrophage ratio were significantly associated with longer overall survival in EC. We also found that the density of CD169(+) macrophages was positively correlated with the number of CD8(+) CTL and CD57(+) NK cells that infiltrated into tumor tissues. A high density of CD57(+) cells in EC tissues was associated with a better prognosis, while a high density of CD8(+) cells was not linked to an altered prognosis. The present study showed that the density of CD169(+) macrophages in RLN was associated with an improved prognosis in EC patients. CD169(+) macrophages in RLN might represent a useful marker for assessing clinical prognoses and monitoring anti-tumor immunity in patients with EC. PMID:26991548

  1. Postoperative vaginal irradiation with high dose rate afterloading technique in endometrial carcinoma stage I

    SciTech Connect

    Sorbe, B.G.; Smeds, A.C. )

    1990-02-01

    A high dose rate ({sup 60}Co) afterloading technique was used for postoperative prophylactic vaginal irradiation in a series of 404 women with endometrial carcinoma Stage I. The total recurrence rate was 3.7% with 0.7% vaginal deposits. The crude 5-year survival rate for the complete series was 91.8% compared to 13.3% for those with recurrences. Depth of myometrial infiltration (greater than 1/3 of the uterine wall) and nuclear grade were the most important prognostic factors. Clinically significant late radiation reactions (bladder and/or rectum) were recorded in 6.9%. Dose per fraction and the size of the target volume were highly significantly related to the occurrence of both early and late radiation reactions. Vaginal shortening is closely related to the dose per fraction, length of the reference isodose, and the applicator diameter. The shape of the vaginal applicator versus the isodoses and the importance of the source train geometry and relative activity for dose gradient inhomogeneities within the target volume are discussed. Cumulative radiation effect (CRE) and linear-quadratic (LQ) calculations have been performed and related to tissue reactions within the target volume and in the risk organs. An alpha-beta quotient of 8.8 for vaginal shrinkage effect and 2.0 for late rectal complications are suggested on the basis of calculations using a maximum likelihood method for quantal radiation data.

  2. miR-205 promotes tumor proliferation and invasion through targeting ESRRG in endometrial carcinoma.

    PubMed

    Su, Ning; Qiu, Haifeng; Chen, Yifei; Yang, Tingting; Yan, Qin; Wan, Xiaoping

    2013-06-01

    Increasing evidence suggests that miR‑205 is frequently dysregulated in many types of human cancers, suggesting its important roles in the initiation and progression of cancer. However, the functions of miR‑205 in human endometrial endometrioid carcinoma (EEC) are still unknown. In this study, we investigated the expression of miR‑205 in both normal endometrium and EEC tissues using TaqMan PCR. Compared to normal tissues, miR‑205 was significantly upregulated in EEC (P<0.001). After transfection of miR‑205 inhibitors into Ishikawa cells (or transfection of miR‑205 mimics into AN3CA cells), we demonstrated that the cellular proliferation, migration and invasion properties were negatively regulated by miR‑205. Moreover, by combination of microRNA target prediction algorithms and luciferase reporter system, we identified estrogen-related receptor‑γ (ESRRG) as a target of miR‑205. In conclusion, we demonstrated frequent upregulation of miR‑205 in EEC. In gain‑of‑function and loss‑of‑function assays, inhibition of miR‑205 reduced cellular proliferation, migration and invasion; vice versa, increased levels of miR‑205 led to upregulated cellular proliferation, migration and invasion. Nonetheless, we identified the ESRRG gene to be a novel target, which could be helpful to elucidate mechanisms underlying the tumorigenesis of EEC. PMID:23589079

  3. Immediate versus delayed hysterectomy for endometrial carcinoma: surgical morbidity and hospital stay

    SciTech Connect

    Chambers, J.T.; Kapp, D.S.; Lawrence, R.; Kohorn, E.I.; Schwartz, P.E.

    1985-02-01

    A retrospective review presented is of the intraoperative complications, postoperative morbidity, and length of hospitalization in 138 patients with stage I endometrial carcinoma treated at Yale-New Haven Hospital from January 1, 1977 to December 31, 1981. One group (stage IA, grade 1) was treated with surgery alone; two groups were treated with preoperative intracavitary radium, followed with either an immediate or a delayed hysterectomy. The three groups were comparable in age, weight, and major preoperative medical problems. The mean estimated blood loss during surgery and transfusion requirements during hospitalization were similar for all three groups. The duration of the surgery in the immediate group was longer than the other two groups. The occurrence of febrile morbidity and major postoperative complications in the three groups was similar, except for bacteriuria, which was significantly more common in the immediate group. The length of the postoperative hospitalization was the same for each group; however, the delayed group as compared with the immediate group had a total hospitalization of two days longer. Hence, in the current study, immediate hysterectomy did not significantly increase the surgical or postoperative morbidity rate, compared with delayed hysterectomy. The single hospital stay in the former treatment group represented cost containment.

  4. Upregulation of microRNA‑337 promotes the proliferation of endometrial carcinoma cells via targeting PTEN.

    PubMed

    Cai, Yangyang; He, Tao; Liang, Lidan; Zhang, Xin; Yuan, Hongying

    2016-06-01

    Endometrial carcinoma (EC) is a common malignancy in females. MicroRNAs (miRs) are a class of non‑coding RNA that regulate a wide variety of cellular processes, and are important in the development of multiple types of malignancy. In the present study, cancerous and adjacent non‑cancerous normal tissue samples were collected from 24 patients diagnosed with EC. Reverse transcription quantitative polymerase chain reaction was performed on the tissue samples to determine the expression levels of six candidate miRs. These miRs have been previously reported to be differentially expressed in EC; however, the present study observed that only miR‑337 was differentially expressed. In addition, the current study identified phosphatase and tensin homolog (PTEN) as a target of miR‑337 using computational analysis and a luciferase assay. EC cells transfected with miR‑337 mimics and anti‑PTEN small interfering RNA demonstrated significantly decreased expression of PTEN, markedly increased proliferation and inhibition of cell apoptosis. The results indicate that miR‑337 is oncogenic in EC cells, as it suppresses PTEN expression. This may facilitate the development of miR‑based prevention or treatment strategies for EC. PMID:27082228

  5. Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

    ClinicalTrials.gov

    2015-11-09

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

  6. Profile of differentially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinoma

    PubMed Central

    ZHANG, XINCHEN; GUO, GORDON; WANG, GUANG; ZHAO, JINYAO; WANG, BO; YU, XIAOTANG; DING, YANFANG

    2015-01-01

    Improved insight into the molecular and genetic profile of different types of epithelial ovarian cancer (EOC) is required for understanding the carcinogenesis of EOC and may potentially be exploited by future targeted therapies. The aim of the present study was to identify a unique microRNA (miRNA) patterns and key miRNAs, which may assist in predicting progression and prognosis in high-grade serous carcinoma (HGSC) and clear cell carcinoma (CCC). To identify unique miRNA patterns associated with HGSC and CCC, a miRNA microarray was performed using Chinese tumor bank specimens of patients with HGSC or CCC in a retrospective analysis. The expression levels of four deregulated miRNAs were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in an external cohort of 42 cases of HGSC and 36 cases of CCC. Kaplan-Meier analysis was performed to analyze the correlation between the expression levels of the four miRNAs and patient prognosis. Among these validated miRNAs, miR-510 was further examined in another cohort of normal ovarian tissues, as well as the HGSC, low-grade serous carcinoma (LGSC) and CCC specimens using RT-qPCR and in situ hybridization. The results revealed that, of the 768 miRNAs analyzed in the microarray, 33 and 50 miRNAs were significantly upregulated and downregulated, respectively, with at least a 2-fold difference in HGSC, compared with CCC. The quantitative analysis demonstrated that miR-510 and miR-129-3p were significantly downregulated, and that miR-483-5p and miR-miR-449a were significantly upregulated in CCC, compared with HGSC (P<0.05), which was consistent with the microarray results. Kaplan-Meier analysis revealed low expression levels of miR-510 and low expression levels of miR-129-3p, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymphatic metastasis and that HGSC was significantly associated with the poorer overall survival rates (P<0.05). The expression of miR-510

  7. The modularity and dynamicity of miRNA-mRNA interactions in high-grade serous ovarian carcinomas and the prognostic implication.

    PubMed

    Zhang, Wensheng; Edwards, Andrea; Fan, Wei; Flemington, Erik K; Zhang, Kun

    2016-08-01

    Ovarian carcinoma is the fifth-leading cause of cancer death among women in the United States. Major reasons for this persistent mortality include the poor understanding of the underlying biology and a lack of reliable biomarkers. Previous studies have shown that aberrantly expressed MicroRNAs (miRNAs) are involved in carcinogenesis and tumor progression by post-transcriptionally regulating gene expression. However, the interference of miRNAs in tumorigenesis is quite complicated and far from being fully understood. In this work, by an integrative analysis of mRNA expression, miRNA expression and clinical data published by The Cancer Genome Atlas (TCGA), we studied the modularity and dynamicity of miRNA-mRNA interactions and the prognostic implications in high-grade serous ovarian carcinomas. With the top transcriptional correlations (Bonferroni-adjusted p-value<0.01) as inputs, we identified five miRNA-mRNA module pairs (MPs), each of which included one positive-connection (correlation) module and one negative-connection (correlation) module. The number of miRNAs or mRNAs in each module varied from 3 to 7 or from 2 to 873. Among the four major negative-connection modules, three fit well with the widely accepted miRNA-mediated post-transcriptional regulation theory. These modules were enriched with the genes relevant to cell cycle and immune response. Moreover, we proposed two novel algorithms to reveal the group or sample specific dynamic regulations between these two RNA classes. The obtained miRNA-mRNA dynamic network contains 3350 interactions captured across different cancer progression stages or tumor grades. We found that those dynamic interactions tended to concentrate on a few miRNAs (e.g. miRNA-936), and were more likely present on the miRNA-mRNA pairs outside the discovered modules. In addition, we also pinpointed a robust prognostic signature consisting of 56 modular protein-coding genes, whose co-expression patterns were predictive for the survival

  8. Endometrial carcinoma located in the right septate uterus cavity: a case report

    PubMed Central

    Boubess, Ikram; Mahdi, Youssef; Ramsiss, Hanan; Filali, Adib; Alami, Mohamad Hassan; El khannoussi, Basma; Hachi, Hafid

    2015-01-01

    Endometrial cancer in patients with uterine congenital malformations is exceptional and there are only a few rare cases published in the literature. We report the case of a 67 years-old patient with an endometrial cancer located in the right cavity of a complete septate uterus. PMID:26958135

  9. Upregulation of TrkB Promotes Epithelial-Mesenchymal Transition and Anoikis Resistance in Endometrial Carcinoma

    PubMed Central

    Bao, Wei; Qiu, Haifeng; Yang, Tingting; Luo, Xin; Zhang, Huijuan; Wan, Xiaoping

    2013-01-01

    Mechanisms governing the metastasis of endometrial carcinoma (EC) are poorly defined. Recent data support a role for the cell surface receptor tyrosine kinase TrkB in the progression of several human tumors. Here we present evidence for a direct role of TrkB in human EC. Immunohistochemical analysis revealed that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are more highly expressed in EC than in normal endometrium. High TrkB levels correlated with lymph node metastasis (p<0.05) and lymphovascular space involvement (p<0.05) in EC. Depletion of TrkB by stable shRNA-mediated knockdown decreased the migratory and invasive capacity of cancer cell lines in vitro and resulted in anoikis in suspended cells. Conversely, exogenous expression of TrkB increased cell migration and invasion and promoted anoikis resistance in suspension culture. Furthermore, over-expression of TrkB or stimulation by BDNF resulted in altered the expression of molecular mediators of the epithelial-to-mesenchymal transition (EMT). RNA interference (RNAi)-mediated depletion of the downstream regulator, Twist, blocked TrkB-induced EMT-like transformation. The use of in vivo models revealed decreased peritoneal dissemination in TrkB-depleted EC cells. Additionally, TrkB-depleted EC cells underwent mesenchymal-to-epithelial transition and anoikis in vivo. Our data support a novel function for TrkB in promoting EMT and resistance to anoikis. Thus, TrkB may constitute a potential therapeutic target in human EC. PMID:23936232

  10. Endometrial ablation

    MedlinePlus

    Hysteroscopy-endometrial ablation; Laser thermal ablation; Endometrial ablation-radiofrequency; Endometrial ablation-thermal balloon ablation; Rollerball ablation; Hydrothermal ablation; Novasure ablation

  11. Use of a human endometrial carcinoma cell line (RL-95) for in vitro testing of chemotherapeutic agents

    SciTech Connect

    Christensen, C.; Deppe, G.; Saunders, D.; Malviya, V.

    1987-09-01

    RL-95, a moderately well-differentiated adenosquamous endometrial carcinoma cell line, can be used as a model for testing chemotherapeutic agents in vitro. Cells are grown in T-75 flasks, transferred to scintillation vials, and grown for 24 hr. Following this, medium is removed and new medium containing Adriamycin (Adr) and cis-platinum (CP) is added. Effects of the two drugs are measured by cell counts and DNA synthesis. To measure DNA synthesis, cells are incubated with (/sup 3/H)thymidine (/sup 3/H-THY) for up to 24 hr. Decreased DNA synthesis is reflected in decreased /sup 3/H-THY uptake. Cell kill is obtained with levels of drugs that are clinically achievable. Evidence is presented for increased cytotoxicity with concomitant, rather than sequential, chemotherapy. Results are also confirmed by testing the agent on MCF-7, a well-known breast cancer cell line. The results indicate that (1) endometrial carcinoma responds to Adriamycin and cis-platinum chemotherapeutic agents in vitro, and (2) RL-95 can be used as a model for testing varying concentrations, time of exposure, and combinations of chemotherapeutic agents.

  12. Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer

    ClinicalTrials.gov

    2014-12-23

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  13. Interval Between Hysterectomy and Start of Radiation Treatment Is Predictive of Recurrence in Patients With Endometrial Carcinoma

    SciTech Connect

    Cattaneo, Richard; Hanna, Rabbie K.; Jacobsen, Gordon; Elshaikh, Mohamed A.

    2014-03-15

    Purpose: Adjuvant radiation therapy (RT) has been shown to improve local control in patients with endometrial carcinoma. We analyzed the impact of the time interval between hysterectomy and RT initiation in patients with endometrial carcinoma. Methods and Materials: In this institutional review board-approved study, we identified 308 patients with endometrial carcinoma who received adjuvant RT after hysterectomy. All patients had undergone hysterectomy, oophorectomy, and pelvic and para-aortic lymph node evaluation from 1988 to 2010. Patients' demographics, pathologic features, and treatments were compared. The time interval between hysterectomy and the start of RT was calculated. The effects of time interval on recurrence-free (RFS), disease-specific (DSS), and overall survival (OS) were calculated. Following univariate analysis, multivariate modeling was performed. Results: The median age and follow-up for the study cohort was 65 years and 72 months, respectively. Eighty-five percent of the patients had endometrioid carcinoma. RT was delivered with high-dose-rate brachytherapy alone (29%), pelvic RT alone (20%), or both (51%). Median time interval to start RT was 42 days (range, 21-130 days). A total of 269 patients (74%) started their RT <9 weeks after undergoing hysterectomy (group 1) and 26% started ≥9 weeks after surgery (group 2). There were a total of 43 recurrences. Tumor recurrence was significantly associated with treatment delay of ≥9 weeks, with 5-year RFS of 90% for group 1 compared to only 39% for group 2 (P<.001). On multivariate analysis, RT delay of ≥9 weeks (P<.001), presence of lymphovascular space involvement (P=.001), and higher International Federation of Gynecology and Obstetrics grade (P=.012) were independent predictors of recurrence. In addition, RT delay of ≥9 weeks was an independent significant predictor for worse DSS and OS (P=.001 and P=.01, respectively). Conclusions: Delay in administering adjuvant RT after hysterectomy was

  14. Tibial bone metastasis as an initial presentation of endometrial carcinoma diagnosed by fine-needle aspiration cytology: A case report and review of the literature

    PubMed Central

    Boukhar, Sarag Aboujafar; Kaneshiro, Ricky; Schiller, Alan; Terada, Keith; Tauchi-Nishi, Pamela

    2015-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States. However, bony metastasis is infrequent and exceptionally rare as the initial presentation. We report a case of a 77-year-old female with a clinically silent endometrial carcinoma who presented with a left tibial metastasis as the first manifestation of her disease. Ours is only the third case diagnosed by fine-needle aspiration (FNA) cytology, and the first to detail the cytomorphologic features of metastatic endometrial cancer to bone. These microscopic findings, including three-dimensional cohesive clusters with cellular overlapping and cuboidal to columnar cells exhibiting low nuclear: cytoplasmic ratios and partially vacuolated cytoplasm, differ significantly from those of endometrial carcinoma on a Papanicolaou test. The tumor bore similarity to the more commonly encountered metastatic colon cancer, but immunohistochemical staining enabled reliable distinction between these entities. A review of osseous metastases of endometrial cancer demonstrates a predilection for bones of the lower extremity and pelvis with a predominance of the endometrioid histologic subtype. In about a quarter of the cases, the bony metastasis was the first manifestation of the cancer. FNA was an effective diagnostic modality for this unusual presentation of a common malignancy. Awareness of this entity and its differential diagnosis is essential for accurate and timely diagnosis. PMID:26085835

  15. Dasatinib in Treating Patients With Recurrent or Persistent Ovarian, Fallopian Tube, Endometrial or Peritoneal Cancer

    ClinicalTrials.gov

    2016-09-08

    Endometrial Clear Cell Adenocarcinoma; Estrogen Receptor Negative; Ovarian Clear Cell Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

  16. Management of endometrial precancers.

    PubMed

    Trimble, Cornelia L; Method, Michael; Leitao, Mario; Lu, Karen; Ioffe, Olga; Hampton, Moss; Higgins, Robert; Zaino, Richard; Mutter, George L

    2012-11-01

    In the United States, endometrial cancer is the most commonly diagnosed cancer of the female reproductive system. Strategies to sensitively and accurately diagnose premalignant endometrial lesions are sorely needed. We reviewed studies pertaining to the diagnostic challenges of endometrial precancers, their predictive value, and evidence to support management strategies. Currently, two diagnostic schemas are in use: the four-class 1994 World Health Organization hyperplasia system, based on morphologic features of architectural complexity and nuclear atypia and, more recently, the two-class endometrial intraepithelial neoplasia system, which is quantitative. Diagnosis should use criteria and terminology that distinguish between clinicopathologic entities that can be managed differently. In some instances, such as for women with hereditary nonpolyposis colon cancer, biomarkers may aid in diagnosis, but the clinical utility of biomarkers has yet to be determined. Total hysterectomy is curative for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, and provides a definitive standard for assessment of a concurrent carcinoma, when clinically appropriate. If hysterectomy is performed for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, then intraoperative assessment of the uterine specimen for occult carcinoma is desirable, but optional. Nonsurgical management may be appropriate for patients who wish to preserve fertility or those for whom surgery is not a viable option. Treatment with progestin therapy may provide a safe alternative to hysterectomy; however, clinical trials of hormonal therapies for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia have not yet established a standard regimen. Future studies will need to determine the optimal nonsurgical management of atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, standardizing agent, dose, schedule, clinical outcomes

  17. The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis.

    PubMed

    Gibson, William J; Hoivik, Erling A; Halle, Mari K; Taylor-Weiner, Amaro; Cherniack, Andrew D; Berg, Anna; Holst, Frederik; Zack, Travis I; Werner, Henrica M J; Staby, Kjersti M; Rosenberg, Mara; Stefansson, Ingunn M; Kusonmano, Kanthida; Chevalier, Aaron; Mauland, Karen K; Trovik, Jone; Krakstad, Camilla; Giannakis, Marios; Hodis, Eran; Woie, Kathrine; Bjorge, Line; Vintermyr, Olav K; Wala, Jeremiah A; Lawrence, Michael S; Getz, Gad; Carter, Scott L; Beroukhim, Rameen; Salvesen, Helga B

    2016-08-01

    Recent studies have detailed the genomic landscape of primary endometrial cancers, but the evolution of these cancers into metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed The Cancer Genome Atlas (TCGA) data, identifying new recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor gene NRIP1 in 12% of patients. We found that likely driver events were present in both primary and metastatic tissue samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses indicated that the sampled metastases typically arose from a common ancestral subclone that was not detected in the primary tumor biopsy. These data demonstrate extensive genetic heterogeneity in endometrial cancers and relative homogeneity across metastatic sites. PMID:27348297

  18. Diagnostic Accuracy of MRI, DWI MRI, FDG-PET/CT and FEC PET/CT in the Detection of Lymph Node Metastases in Surgically Staged Endometrial and Cervical Carcinoma

    ClinicalTrials.gov

    2016-01-21

    Surgically Staged Endometrial and Cervical Carcinoma; Cervical Cancer: Invasive Disease, FIGO Stage 1B1 or Higher; Endometrial Cancer:; Stage 1A With Myometrial Invasion or Any Higher Stage and Grade 3; Stage 1A With Myometrial Invasion or Any Other Higher Stage and Serous Papillary or Clear Cell Sub-types; Stage II Disease or Above and Any Histology Grade

  19. Combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro

    PubMed Central

    Erguven, Mine; Ermis, Ezgi; Sencan, Mine; Yazihan, Nuray

    2011-01-01

    Objective The aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies. Methods Imatinib mesylate (50 µM), lithium chloride (100 µM), medroxyprogesterone acetate (200 µM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student's t-test. Results All drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05). Conclusion The present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense. PMID:22247798

  20. Inhibition of Adhesion, Proliferation, and Invasion of Primary Endometriosis and Endometrial Stromal and Ovarian Carcinoma Cells by a Nonhyaluronan Adhesion Barrier Gel

    PubMed Central

    Renner, Stefan P.; Strissel, Pamela L.; Beckmann, Matthias W.; Lermann, Johannes; Hackl, Janina; Fasching, Peter A.

    2015-01-01

    Endometriosis is a chronic disease of women in the reproductive age, defined as endometrial cells growing outside of the uterine cavity and associated with relapses. Relapses are hypothesized to correlate with incomplete surgical excision or result from nonrandom implantation of new endometrial implants in adjacent peritoneum. Thus, surgical excision could lead to free endometriotic cells or tissue residues, which readhere, grow, and invade into recurrent lesions. Barrier agents are frequently used to prevent postoperative adhesions. We tested if the absorbable cell adhesion barrier gel Intercoat consisting of polyethylene oxide and sodium carboxymethyl cellulose could inhibit cellular adhesion, proliferation, and invasion of primary endometriosis and endometrial cells. Due to an association of endometriosis with ovarian carcinoma, we tested two ovarian carcinoma cell lines. Prior to cell seeding, a drop of the barrier gel was placed in cell culture wells in order to test inhibition of adherence and proliferation or coated over a polymerized collagen gel to assay for prevention of invasion. Results showed that the barrier gel significantly inhibited cell adherence, proliferation, and invasion of endometriosis and endometrial stromal cells as well as ovarian carcinoma cells in culture. Our findings could help to prevent local cell growth/invasion and possible consequent recurrences. PMID:25785270

  1. EphA2 Targeted Chemotherapy Using an Antibody Drug Conjugate in Endometrial Carcinoma

    PubMed Central

    Lee, Jeong-Won; Stone, Rebecca L.; Lee, Sun Joo; Nam, Eun Ji; Roh, Ju-Won; Nick, Alpa M.; Han, Hee-Dong; Shahzad, Mian M.K.; Kim, Hye-Sun; Mangala, Lingegowda S.; Jennings, Nicholas B.; Mao, Shenlan; Gooya, John; Jackson, Dowdy; Coleman, Robert L.; Sood, Anil K.

    2013-01-01

    Purpose EphA2 overexpression is frequently observed in endometrial cancers, and is predictive of poor clinical outcome. Here, we utilize an antibody drug conjugate (MEDI-547) composed of a fully human monoclonal antibody against both human and murine EphA2 (1C1) and the tubulin polymerization inhibitor, monomethylauristatin F (MMAF). Experimental design EphA2 expression was examined in endometrial cancer cell lines by Western Blot. Specificity of MEDI-547 was examined by antibody degradation and internalization assays. Viability and apoptosis were investigated in endometrial cancer cell lines and orthotopic tumor models. Results EphA2 was expressed in the Hec-1A and Ishikawa cells, but was absent in the SPEC-2 cells. Antibody degradation and internalization assays showed that the antibody drug conjugate decreased EphA2 protein levels and was internalized in EphA2 positive cells (Hec-1A and Ishikawa). Moreover, in vitro cytotoxicity and apoptosis assays demonstrated that the antibody drug conjugate decreased viability and increased apoptosis of Hec-1A and Ishikawa cells. In vivo therapy experiments in mouse orthotopic models with this antibody drug conjugate resulted in 86 to 88% growth inhibition (P < 0.001) in the orthotopic Hec-1A and Ishikawa models compared to controls. Moreover, the mice treated with this antibody drug conjugate had a lower incidence of distant metastasis compared with controls. The anti-tumor effects of the therapy were related to decreased proliferation and increased apoptosis of tumor and associated endothelial cells. Conclusions The preclinical data for endometrial cancer treatment using MEDI-547 demonstrate substantial anti-tumor activity. PMID:20388851

  2. Urokinase-type Plasminogen Activator Resulting from Endometrial Carcinogenesis Enhances Tumor Invasion and Correlates with Poor Outcome of Endometrial Carcinoma Patients

    PubMed Central

    Huang, Chia-Yen; Chang, Ming-Cheng; Huang, Wei-Yun; Huang, Ching-Ting; Tang, Yu-Chien; Huang, Hsien-Da; Kuo, Kuan-Ting; Chen, Chi-An; Cheng, Wen-Fang

    2015-01-01

    The purpose of this study was to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC), and their possible mechanisms. Endometrial specimens including normal endometrial tissues, atypical endometrial hyperplasia, and EEC were analyzed. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by real-time RT-PCR in the training and testing sets to correlate the clinico-pathological parameters of EEC. Immunoblotting, in vitro cell migration and invasion assays were performed in human endometrial cancer cell lines and their transfectants. In microarray analysis, seven dysregulated genes were identified. Only the levels of urokinase-type plasminogen activator (uPA) were higher in EEC with deep myometrial invasion, positive lympho-vascular space invasion, lymph node metastasis, and advanced stages. After multivariate analysis, uPA was the only independent poor prognostic factor for disease-free survival in the EEC patients (hazard ratio: 4.65, p = 0.03). uPA may enhance the migratory and invasive capabilities of endometrial tumor cells by the phosphorylation of ERK1/2, Akt and p38 molecules. uPA is a dysregulated gene involved in the tumorigenesis, bio-pathological features and outcomes of EEC. uPA may be a potential molecule and target for the detection and treatment of EEC. PMID:26033187

  3. Treatment with Tie2-siRNA in combination with carboplatin suppresses the growth of Ishikawa human endometrial carcinoma cell xenografts in vivo

    PubMed Central

    GUO, FEIFEI; XUN, QINGYING; ZHOU, HUAIJUN

    2013-01-01

    It is well-known that tumor angiogenesis is important in cancer development, and studies on blocking angiogenesis to treat tumors have become one of the most promising and active fields in anticancer research. The present study investigated the effect of siRNA targeting the tyrosine kinase receptor 2 (Tie2) gene in combination with carboplatin in a mouse model of endometrial carcinoma in an attempt to elucidate the role of Tie2 in the carcinogenesis and progression of endometrial carcinoma via angiogenesis, in order to establish a basis for the development of complementary molecule targeting and chemotherapeutic actions. Ishikawa cells were used to establish a human endometrial carcinoma nude mouse tumor xenograft model. Tie2-siRNA (20 μg/mouse) and/or carboplatin (25.0 mg·kg−1) were administered as the treatment strategy. Real-time PCR and western blotting were used to evaluate the expression levels of Tie2 mRNA and protein and immunohistochemistry was used to assess the vessel density of the tumor tissues. The present data demonstrated that Tie2-siRNA and/or carboplatin were able to suppress the growth of endometrial xenografts in vivo and attenuate the expression of Tie2 mRNA and protein, as assessed by real-time PCR and western blotting. Furthermore, immunohistochemical assessment showed that the vessel density of the tumors decreased with treatment. The present results suggest that treatment with Tie2-siRNA or carboplatin alone was able to inhibit the growth of human endometrial carcinoma nude mouse xenografts markedly and decrease the expression of Tie2. The combination of Tie2-siRNA and carboplatin increased the therapeutic effect of carboplatin which may eliminate the tumor microenvironment, increase the apoptosis of tumor cells, normalize the abnormal tumor vessels and increase the efficiency of chemotherapy for endometrial carcinoma with carboplatin. The synergy of Tie2-siRNA in combination with carboplatin may involve the regulation of other

  4. Insights into endometrial serous carcinogenesis and progression.

    PubMed

    Fadare, Oluwole; Zheng, Wenxin

    2009-01-01

    Endometrial serous carcinomas (ESC) constitute only approximately 10% of endometrial cancers, but have a substantially higher case-fatality rate than their more common endometrioid counterparts. The precise composite of factors driving endometrial serous carcinogenesis and progression remain largely unknown, but we attempt to review the current state of knowledge in this report. ESC probably do not evolve through a single pathway, and their underlying molecular events probably occur early in their evolution. TP53 gene mutations occur in 22.7 to 96% of cases, and p53 protein overexpression is seen in approximately 76%. By gene expression profiling, p16 is upregulated in ESC significantly above both normal endometrial cells and endometrioid carcinomas, and 92-100% of cases display diffuse expression of the p16 protein by immunohistochemistry (IHC). Together, these findings suggest dysregulation of both the p16(INKA)/Cyclin D-CDK/pRb-E2F and the ARF-MDM2-p53 cell cycle pathways in ESC. By IHC, HER2/neu is overexpressed (2+ or 3+) in approximately 32.1% of ESC, and approximately 54.5% of cases scored as 2+ or 3+ by IHC display c-erbB2 gene amplification as assessed by fluorescent in situ hybridization. Genetic instability, typically manifested as loss of heterozygosity in multiple chromosomes, is a common feature of ESC, and one study found loss of heterozygosity at 1p32-33 in 63% of cases. A subset of ESC display protein expression patterns that are characteristic of high grade endometrial carcinomas, including loss of the metastasis suppressor CD82 (KAI-1) and epithelial-to-mesenchymal transformation, the latter manifested as E-cadherin downregulation, P-cadherin upregulation, and expression of epithelial-to-mesenchymal transformation-related molecules such as zinc-finger E-box-binding homeobox 1 (ZEB1) and focal adhesion kinase. Preliminary data suggests differential patterns of expression in ESC of some isoforms of claudins, proteases, the tumor invasiveness and

  5. Management of Endometrial Precancers

    PubMed Central

    Trimble, Cornelia L.; Method, Michael; Leitao, Mario; Lu, Karen; Ioffe, Olga; Hampton, Moss; Higgins, Robert; Zaino, Richard; Mutter, George L.

    2013-01-01

    In the United States, endometrial cancer is the most commonly diagnosed cancer of the female reproductive system. Strategies to sensitively and accurately diagnose premalignant endometrial lesions are sorely needed. We reviewed studies pertaining to the diagnostic challenges of endometrial precancers, their predictive value, and evidence to support management strategies. Currently, two diagnostic schema are in use; the 4-class WHO94 hyperplasia system, based on morphologic features of architectural complexity and nuclear atypia, and more recently, the 2-class endometrial intraepithelial neoplasia system, which is quantitative. Diagnosis should employ criteria and terminology which distinguish between clinicopathologic entities that can be managed differently. In some instances, such as for women with hereditary nonpolyposis colon cancer (HNPCC), biomarkers may aid in diagnosis, but the clinical utility of biomarkers has yet to be determined. Total hysterectomy is curative for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, and provides a definitive standard for assessment of a concurrent carcinoma, where clinically appropriate. If hysterectomy is performed for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, intraoperative assessment of the uterine specimen for occult carcinoma is desirable, but optional. Nonsurgical management may be appropriate for patients who wish to preserve fertility or those for whom surgery is not a viable option. Treatment with progestin therapy may provide a safe alternative to hysterectomy; however, clinical trials of hormonal therapies for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia have not yet established a standard regimen. Future studies will need to determine the optimal non-surgical management of AEH/EIN, standardizing agent, dose, schedule, clinical outcomes, and appropriate follow-up. PMID:23090535

  6. Synchronous ovarian and endometrial carcinomas in a patient with Rubinstein-Taybi syndrome: a case report and literature review.

    PubMed

    Johannesen, Eric J; Williams, Todd; Miller, Douglas C; Tuller, Erin

    2015-03-01

    Rubinstein-Taybi syndrome is characterized by distinctive facial and limb features and is associated with several types of tumors. A 29-yr-old woman with this syndrome presented with a large, complex ovarian mass. She was subsequently diagnosed with a low-grade serous carcinoma of the ovary and an endometrioid adenocarcinoma of the uterus. Rubinstein-Taybi syndrome is an autosomal dominant, multiple congenital anomalies-mental retardation syndrome. Two genes, CREBBP and EP300, have been found to be associated with this disorder, although some cases do not have an identifiable cause. These genes code for proteins that acetylate histone tails, an epigenetic modification that serves to control transcription. They also serve as cofactors to several transcription factors and modulate p53. Although these patients have a predisposition to benign and malignant neoplasms, no malignant gynecologic neoplasm has been described thus far. Although no significant evidence linking CREBBP and EP300 to gynecologic malignancies has yet been found, some studies have suggested that hypoacetylation of histones may be involved in endometrial and ovarian carcinomas. PMID:25675181

  7. Endometrial cancer

    MedlinePlus

    ... Endometrial biopsy Dilation and curettage ( D and C ) Pap smear (may raise a suspicion for endometrial cancer, but ... for more than 2 years. Frequent pelvic exams, Pap smears and endometrial biopsy may be considered in some ...

  8. Critical analysis of cases of endometrial carcinoma of the uterine corpus incidentally diagnosed after incomplete surgery for other indications. Three case reports and a review of the literature

    PubMed Central

    Wielgoś, Mirosław; Panek, Grzegorz

    2014-01-01

    Incidental diagnosis of endometrial carcinoma after the operation for presumed benign disease is rare. At present, there are no recognized guidelines on optimal management of uterine malignancy diagnosed after incomplete surgery for other indications and the reported experience is limited. Although the risk of histological diagnosis of endometrial carcinoma in the uterus removed for pre-operatively diagnosed benign disease is very low, one should always bear in mind that it may indeed occur. Omission of certain diagnostic procedures prior to hysterectomy may result in incidental finding of a malignancy at or after surgery, even when preoperative imaging studies reveal benign disease. Many centres develop their own strategies, although in most cases the adnexa and cervix are removed and thorough exploration of the abdominal cavity is performed. Also, in view of the technical difficulties involved in removing the uterus and adnexa via the vagina and a potential high risk of cancer either developing in the cervical stump or disseminated from inadvertently morcellated uterine fragments, one should carefully consider the potential benefits and risks of supracervical hysterectomy. We present three patients with endometrial carcinoma diagnosed after hysterectomy, who subsequently underwent completion surgery. A review of the literature follows, which presents opinions from international centres. PMID:26327871

  9. Treatment Outcomes and Prognostic Factors in Mexican Patients with Endometrial Carcinoma with Emphasis on Patients Receiving Radiotherapy after Surgery: An Institutional Perspective

    PubMed Central

    Flores, Christian; Mariscal, Carlos; Celis, Alfredo; Balcázar, Nidia M.; Meneses, Abelardo; Mohar, Alejandro; Mota, Aida; Trejo, Elizabeth

    2012-01-01

    Aim. To analyze the clinical characteristics and treatment outcomes in patients with endometrial carcinoma treated in a Latin American institute with emphasis in patients receiving adjuvant radiotherapy. Methods. A total of 412 patients with endometrial carcinoma admitted to our hospital between 1998 and 2008 were evaluated, retrospectively. The mean age was 55 years (28–87). Two hundred seventy patients received RT following surgery. Stage distribution was as follows: 221 patients (54%) stage I, 86 patients (21%) stage II, and 103 patients (24.5%) stage III and 2 patients (0.5%) stage IVA. Results. Overall survival rate was 95% at 2 years, 84% at 5 years, and 79% at 10 years. By the end of followup, 338 patients (82%) were disease-free, and 13 (3%) were alive with disease. Univariate and multivariate analyses identified age, grade, serosal and adnexial involvement as significant predictors for overall survival. Conclusion. The results of our study suggests that early-stage, low-grade endometrial cancer with no risk factors should not receive external beam radiotherapy, intermediate risk patients should receive only vaginal vault brachytherapy, and the use of chemotherapy with radiotherapy for patients high-risk and advanced-stage carcinoma the addition of radiotherapy is associated with a better survival being an effective therapeutic option. PMID:22675641

  10. Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice.

    PubMed

    Buza, Natalia; English, Diana P; Santin, Alessandro D; Hui, Pei

    2013-12-01

    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

  11. The rs6983267 SNP and long non-coding RNA CARLo-5 are associated with endometrial carcinoma.

    PubMed

    Zhao, Xiwa; Wei, Xurui; Zhao, Lianmei; Shi, Li; Cheng, Jianxin; Kang, Shan; Zhang, Hui; Zhang, Jun; Li, Li; Zhang, Haibo; Zhao, Wei

    2016-08-01

    The single nucleotide polymorphism (SNP) rs6983267 and cancer-associated region long non-coding RNA (CARLo-5) are associated with various human cancers. This study aimed to investigate the expression of CARLo-5 in endometrial carcinoma (EC) and its relationship with clinicopathological features and patient survival. The association of the rs6983267 SNP with EC risk and its involvement in the regulation of CARLo-5 expression in EC were investigated. The rs6983267 SNP was genotyped by polymerase chain reaction (PCR) and ligase detection reaction in 543 EC patients and 584 controls. The expression of CARLo-5 in 108 EC tissues and 66 normal endometrial tissues (NETs) was determined using quantitative real-time PCR. The genotype and allele distributions of the rs6983267 SNP differed significantly between patients and controls. There was a significant correlation between the rs6983267 genotypes and lymph node metastasis of EC patients (P = 0.026). CARLo-5 expression was significantly higher in EC tissues than in NETs (P < 0.001) and significantly associated with FIGO stage (P = 0.029) and lymph node metastasis (P = 0.030). Patients with high CARLo-5 expression had significantly shorter overall survival than those with low CARLo-5 expression (P = 0.003). The rs6983267 genotype was significantly correlated with CARLo-5 expression (P < 0.05). In conclusion, CARLo-5 was identified as a pro-oncogenic lncRNA that may play an important role in EC progression and represent a prognostic marker for EC. The expression of CARLo-5 was significantly correlated with the rs6983267 genotype associated with increased susceptibility to EC. Environ. Mol. Mutagen. 57:508-515, 2016. © 2016 Wiley Periodicals, Inc. PMID:27432114

  12. The role of radiation therapy in uterine-confined endometrial carcinoma.

    PubMed

    Boyle, John M; Diavolitsis, Virginia M; Small, William

    2011-01-01

    The treatment of endometrial cancer begins with surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal lavage, and a consideration for lymph node evaluation. Selection of adjuvant therapy is based on an approximation of the risk of recurrence with features such as stage, tumor histology, lymphovascular space invasion, and patient age. The role of adjuvant radiation therapy in patients with intermediate risk of recurrence is a matter of ongoing controversy. Several randomized trials indicate that adjuvant radiation therapy improves loco-regional control. However, the ideal form of radiation therapy in these patients continues to be under debate. PMID:24673950

  13. The secondary Müllerian system, field effect, BRCA, and tubal fimbria: our evolving understanding of the origin of tubo-ovarian high-grade serous carcinoma and why assignment of primary site matters.

    PubMed

    Singh, Naveena; Gilks, C Blake; Wilkinson, Nafisa; McCluggage, W Glenn

    2015-08-01

    It has long been held that most epithelial ovarian carcinomas arise from the ovarian surface epithelium. Theories on origin were based on the assumption that there was a common cell of origin for all ovarian carcinoma histotypes, and that these histotypes were closely related and frequently admixed. It is now recognised that the histotypes are distinct diseases. Recent studies on early, organ-confined, non-uterine high-grade serous carcinoma (HGSC) have led to a change in our understanding of their anatomical site of origin. These studies were initially on patients at high risk of developing HGSC but more recently have been extended to cases without family history or genetic markers of increased risk. These have shown that incidental HGSC, when detected before dissemination, is most commonly identified in the tubal fimbria. As a result, we have had to revisit theories on the cell and site of origin of HGSC. This progress in our understanding has necessitated a change in how we handle cases in clinical practice, as it impacts on primary site assignment, which in turn has implications for staging. In this review we will discuss the evolution of our understanding of the cell of origin of HGSC, the evidence for the tubal fimbria as the anatomical site of origin of most non-uterine HGSC, and the clinical implications of these recent developments. PMID:26126051

  14. Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium

    PubMed Central

    Bartosch, Carla; Monteiro-Reis, Sara; Almeida-Rios, Diogo; Vieira, Renata; Castro, Armando; Moutinho, Manuel; Rodrigues, Marta; Graça, Inês

    2016-01-01

    Sirtuins participate in hormone imbalance, metabolism and aging, which are important processes for endometrial cancer (EC) development. Sirtuins mRNA expression (SIRT1 to 7) was determined in 76 ECs (63 Type I, 12 Type II and one mixed EC), and 30 non-neoplastic endometria (NNE) by quantitative real-time PCR. SIRT1 and SIRT7 protein expression was evaluated by immunohistochemistry using Allred score. Compared to NNE, ECs showed SIRT7 (p < 0.001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed. No significant differences were observed for SIRT3 and SIRT6. Type II ECs displayed lower SIRT1 (p = 0.032) and SIRT3 (p = 0.016) transcript levels than Type I ECs. Concerning protein expression, SIRT1 immunostaining median score was higher in ECs compared to NNE epithelium (EC = 5 vs. NNE = 2, p < 0.001), while SIRT7 was lower in ECs (EC = 6 vs. NNE = 7, p < 0.001). No significant associations were found between SIRT1/7 immunoexpression and histological subtype, grade, lymphovascular invasion or stage. Our data shows that sirtuins are deregulated in EC. The diversity of expression patterns observed suggests that sirtuins may have distinctive roles in endometrial cancer similarly to what has been described in other cancer models. PMID:26701732

  15. Spontaneous Occurrence of Gangrene Due to Clostridium septicum in a Patient With Advanced Endometrial Carcinoma

    PubMed Central

    Ghosh, Kris; Sutton, Gregory P.

    1994-01-01

    Background: We report the first known case of spontaneous, atraumatic Clostridium septicum gangrene occurring in a patient with recurrent endometrial adenocarcinoma. Case: A 63-year-old white female undergoing chemotherapy for recurrent endometrial adenocarcinoma presented with right “arthritis-like” shoulder pain. She denied fever, chills, or shoulder trauma. The patient was afebrile and her blood pressure was 100/50. Her right shoulder and upper extremity were remarkable for an area of dark blue discoloration with crepitus. The white blood cell (WBC) count was 8,200/μl with left shift. Serum creatinine, platelet count, and coagulation studies were normal. Computed tomography revealed gas in the right shoulder tissues. A Gram stain of fluid aspirated from the shoulder demonstrated gram-positive spore-forming rods. She declined surgical intervention and expired within hours of admission. Cultures of the right shoulder eventually grew Clostridium septicum. Conclusion: It is imperative to consider clostridial gangrene in the differential diagnosis for any patient with cancer and a fever of unknown origin. PMID:18475364

  16. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma

    PubMed Central

    Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-01

    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

  17. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    SciTech Connect

    Elshaikh, Mohamed A.; Vance, Sean; Suri, Jaipreet S.; Mahan, Meredith; Munkarah, Adnan

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  18. A comparison of extraperitoneal versus transperitoneal laparoscopic para-aortic lymphadenectomy for staging of endometrial carcinoma

    PubMed Central

    Pakish, Janelle; Soliman, Pamela T.; Frumovitz, Michael; Westin, Shannon N.; Schmeler, Kathleen M.; dos Reis, Ricardo; Munsell, Mark F.; Ramirez, Pedro T.

    2014-01-01

    Objective The objective of our study was to compare the surgical outcomes of extraperitoneal laparoscopic, transperitoneal laparoscopic, and robotic transperitoneal para-aortic lymphadenectomy in endometrial cancer staging. Methods A retrospective review was performed from January 2007 to November 2012. Three groups were compared: extraperitoneal laparoscopic para-aortic lymphadenectomy and robotic hysterectomy and pelvic lymphadenectomy (“extraperitoneal group”; N=34); laparoscopic hysterectomy and transperitoneal pelvic and para-aortic lymphadenectomy (“transperitoneal laparoscopic group”; N=108); and robotic hysterectomy and transperitoneal pelvic and para-aortic lymphadenectomy (“transperitoneal robotic group”; N=52). Fisher’s exact test and Kruskal-Wallis test were used for statistical analysis, and statistical significance was defined as P< 0.05. Results Median number of para-aortic lymph nodes obtained was higher in the extraperitoneal group than in the transperitoneal laparoscopic and robotic groups (10, 5, and 4.5 nodes, respectively; P<0.001). Among patients with BMI <35 kg/m2, the median number of para-aortic nodes harvested was higher in the extraperitoneal group than in the transperitoneal laparoscopic and robotic groups (9, 4, and 5 nodes, respectively; P<0.01). The same pattern was observed among patients with BMI ≥35 kg/m2 (10, 6, and 3 nodes, respectively) (P=0.001). There was no significant difference in median estimated blood loss between the extraperitoneal group and either the transperitoneal laparoscopic group (100 vs. 112.5 mL; P=0.06) or the transperitoneal robotic group (100 vs. 67.5 mL; P=0.23). Conclusion Extraperitoneal laparoscopic para-aortic lymphadenectomy resulted in a higher number of para-aortic lymph nodes removed than transperitoneal laparoscopic or robotic lymphadenectomy. The extraperitoneal approach should be considered for endometrial cancer staging. PMID:24361579

  19. Identification of chimeric TSNAX-DISC1 resulting from intergenic splicing in endometrial carcinoma through high-throughput RNA sequencing.

    PubMed

    Li, Na; Zheng, Jian; Li, Hua; Deng, Jieqiong; Hu, Min; Wu, Hongchun; Li, Wei; Li, Fang; Lan, Xun; Lu, Jiachun; Zhou, Yifeng

    2014-12-01

    Gene fusion is among the primary processes that generate new genes and has been well characterized as potent pathway of oncogenesis. Here, by high-throughput RNA sequencing in nine paired human endometrial carcinoma (EC) and matched non-cancerous tissues, we obtained that chimeric translin-associated factor X-disrupted-in-schizophrenia 1 (TSNAX-DISC1) occurred significantly upregulated in multiple EC samples. Experimental investigation showed that TSNAX-DISC1 appears to be formed by splicing without chromosomal rearrangement. The chimera expression inversely correlated with the binding of CCCTC-binding factor (CTCF) to the insulators. Subsequent investigations indicate that long intergenic non-coding RNA lincRNA-NR_034037, separating TSNAX from DISC1, regulates TSNAX -DISC1 production and TSNAX/DISC1 expression levels by extricating CTCF from insulators. Dysregulation of TSNAX influences steroidogenic factor-1-stimulated transcription on the StAR promoter, altering progesterone actions, implying the association with cancer. Together, these results advance our understanding of the mechanism in which lincRNA-NR_034037 regulates TSNAX-DISC1 formation programs that tightly regulate EC development. PMID:25239642

  20. Comparison of high-dose-rate and low-dose-rate brachytherapy in the treatment of endometrial carcinoma

    SciTech Connect

    Fayed, Alaa; Mutch, David G.; Rader, Janet S.; Gibb, Randall K. |; Powell, Matthew A. |; Wright, Jason D.; El Naqa, Issam; Zoberi, Imran |; Grigsby, Perry W. |||. E-mail: pgrigsby@wustl.edu

    2007-02-01

    Purpose: To compare the outcomes for endometrial carcinoma patients treated with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. Methods and Materials: This study included 1,179 patients divided into LDR (1,004) and HDR groups (175). Patients with International Federation of Gynecology and Obstetrics (FIGO) surgical Stages I-III were included. All patients were treated with postoperative irradiation. In the LDR group, the postoperative dose applied to the vaginal cuff was 60-70 Gy surface doses to the vaginal mucosa. The HDR brachytherapy prescription was 6 fractions of 2 Gy each to a depth of 0.5 cm from the surface of the vaginal mucosa. Overall survival, disease-free survival, local control, and complications were endpoints. Results: For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the LDR group were 70%, 69%, and 81%, respectively. For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the HDR group were 68%, 62%, and 78%, respectively. There were no significant differences in early or late Grade III and IV complications in the HDR or LDR groups. Conclusion: Survival outcomes, pelvic tumor control, and Grade III and IV complications were not significantly different in the LDR brachytherapy group compared with the HDR group.

  1. OCT4 pseudogene 5 upregulates OCT4 expression to promote proliferation by competing with miR-145 in endometrial carcinoma.

    PubMed

    Bai, Mingzhu; Yuan, Mu; Liao, Hong; Chen, Jiazhou; Xie, Binying; Yan, Dong; Xi, Xiaowei; Xu, Xianming; Zhang, Zhenbo; Feng, Youji

    2015-04-01

    OCT4 plays a critical role in the maintenance of stem cell pluripotency and proliferation, and is overexpressed in multiple human tumors, including endometrial cancer. OCT4 expression can be modulated by miR-145 and the OCT4 pseudogene 5 (OCT4-pg5), which share similar binding sites in the OCT4 3'-untranslated region. The goal of the present study was to evaluate the interaction between miR-145 and OCT4‑pg5 on OCT4 expression in endometrial cancer. We assessed OCT4-pg5 expression in 14 benign endometrium and 29 endometrial carcinoma samples. Furthermore, miR-145 mimic transfection was performed to explore its effect on OCT4-pg5 and OCT4 expression, and small interfering RNA (siRNA)-mediated knockdown of OCT4 was conducted to determine whether the effect of OCT4-pg5 on cellular growth was OCT4-dependent. We observed that OCT4-pg5 was abnormally activated in the endometrial carcinomas, and that overexpression of OCT4-pg5 contributed to enhanced cell proliferation and OCT4-PI3K/AKT-cyclin D1 signaling. Moreover, the miR-145 mimic depleted OCT4 expression, whereas elevated OCT4-pg5 restored OCT4 expression and OCT4-PI3K/AKT-cyclin D1 signaling. In conclusion, these data indicate that OCT4-pg5 can act as an RNA sponge to protect OCT4 transcripts from being inhibited by miR-145, providing novel insight into the control of OCT4 expression. PMID:25634023

  2. Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

    PubMed Central

    Barlin, Joyce N.; Soslow, Robert A.; Lutz, Megan; Zhou, Qin C.; St Clair, Caryn M.; Leitao, Mario M.; Iasonos, Alexia; Hensley, Martee L.; Barakat, Richard R.; Matias-Guiu, Xavier; Abu-Rustum, Nadeem R.

    2015-01-01

    Objective We propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems. Methods We analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows: IA Low-grade carcinoma with less than half myometrial invasion IA1 Negative nodes IA2 No nodes removed IB High-grade carcinoma with no myometrial invasion IB1 Negative nodes IB2 No nodes removed IC Low-grade carcinoma with half or greater myometrial invasion IC1 Negative nodes IC2 No nodes removed ID High-grade carcinoma with any myometrial invasion ID1 Negative nodes ID2 No nodes removed Results Data from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system. Conclusions By incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas). PMID:24126219

  3. Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets

    PubMed Central

    Thiel, Falk; Wachter, David; Ekici, Arif B.; Wolf, Friedericke; Thieme, Franziska; Ruprecht, Klemens; Beckmann, Matthias W.; Strick, Reiner

    2012-01-01

    Endometrial carcinoma (EnCa) is the most common invasive gynaecologic carcinoma. Over 85% of EnCa are classified as endometrioid, expressing steroid hormone receptors and mostly involving pathological prestages. Human endogenous retroviruses (ERV) are chromosomally integrated genes, account for about 8% of the human genome and are implicated in the etiology of carcinomas. The majority of ERV envelope (env) coding genes are either not present or not consistently represented between common gene expression microarrays. The aim of this study was to analyse the absolute gene expression of all known 21 ERV env genes including 19 codogenic and two env genes with premature stop codons in EnCa, endometrium as well as in hyperplasia and polyps. For EnCa seven env genes had high expression with >200 mol/ng cDNA (e.g. envH1-3, Syncytin-1, envT), two middle >50 mol/ng cDNA (envFc2, erv-3) and 12 low <50 mol/ng cDNA (e.g. Syncytin-2, envV2). Regarding tumor parameters, Syncytin-1 and Syncytin-2 were significantly over-expressed in advanced stage pT2 compared to pT1b. In less differentiated EnCa Syncytin-1, erv-3, envT and envFc2 were significantly over-expressed. Syncytin-1, Syncytin-2 and erv-3 were specific to glandular epithelial cells of polyps, hyperplasia and EnCa using immunohistochemistry. An analysis of 10 patient-matched EnCa with endometrium revealed that the ERV-W 5' long terminal repeat regulating Syncytin-1 was hypomethylated, including the ERE and CRE overlapping MeCP2 sites. Functional analyses showed that 10 env genes were regulated by methylation in EnCa using the RL95-2 cell line. In conclusion, over-expressed env genes could serve as indicators for pathological pre-stages and EnCa. PMID:23085571

  4. Endometrial carcinoma in breast cancer patients treated with tamoxifen. Two case report and review of the literature.

    PubMed

    Lanza, A; Alba, E; Re, A; Tessarolo, M; Leo, L; Bellino, R; Lauricella, A; Wierdis, T

    1994-01-01

    Recent reports suggest an increased incidence of endometrial cancer in breast cancer patients under long-term adjuvant tamoxifen (TAM) treatment. The Authors describe two cases of endometrial adenocarcinoma among 80 post-menopausal patients affected with breast cancer and treated with TAM. PMID:7875160

  5. Endometrioid endometrial adenocarcinoma recurring as carcinosarcoma.

    PubMed

    Shaco-Levy, Ruthy; Piura, Benjamin

    2008-04-01

    Müllerian carcinosarcoma is currently regarded as a metaplastic (sarcomatous) carcinoma. Only five cases of pure ovarian adenocarcinoma recurring as carcinosarcoma have been documented in the literature. There are no documented cases of endometrial adenocarcinoma recurring as metaplastic carcinoma. We report of a case of endometrial adenocarcinoma, endometrioid type, recurring as metaplastic carcinoma showing sarcomatous differentiation. The tumor evolution in this case supports the prevailing opinion that Müllerian carcinosarcomas are derived from carcinomas and represent tumor progression. PMID:18412798

  6. Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition.

    PubMed

    Ma, Si-Rui; Wang, Wei-Ming; Huang, Cong-Fa; Zhang, Wen-Feng; Sun, Zhi-Jun

    2015-04-20

    Anterior gradient protein 2 (AGR2) is a novel biomarker with potential oncogenic role. We sought to investigate the diagnostic and prognostic role of AGR2 on head and neck squamous cell carcinoma (HNSCC) with an emphasis on its correlation of cancer stemloid cells (CSC) and epithelial mesenchymal transition (EMT). We found that AGR2 protein levels were higher in HNSCC than in normal oral mucosa. High levels of AGR2 were associated with the T category, pathological grade and lymph node metastasis of HNSCC. Expression of AGR2 increased in recurring HNSCC after radiotherapy and in post cisplatin-based chemotherapeutic tissues. In HNSCC cell lines, knock-down of AGR2 induced apoptosis, reduced sphere formation, and down-regulated Survivin, Cyclin D1, Bcl2, Bcl2l1, Slug, Snail, Nanog and Oct4. In addition, over-expressed AGR2 in transgenic mice with spontaneous HNSCC was associated with lost function of Tgfbr1 and/ or lost function of Pten. In vitro knockdown TGFBR1 in HNSCC cell lines increased AGR2 expression. These results suggest that AGR2 is involved in EMT and self-renewal of CSC and may present a potential therapeutic target (oncotarget) for HNSCC. PMID:25871396

  7. Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ERα in Tamoxifen-Associated Endometrial Carcinomas.

    PubMed

    Droog, Marjolein; Nevedomskaya, Ekaterina; Kim, Yongsoo; Severson, Tesa; Flach, Koen D; Opdam, Mark; Schuurman, Karianne; Gradowska, Patrycja; Hauptmann, Michael; Dackus, Gwen; Hollema, Harry; Mourits, Marian; Nederlof, Petra; van Boven, Hester; Linn, Sabine C; Wessels, Lodewyk; van Leeuwen, Flora E; Zwart, Wilbert

    2016-07-01

    Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERα was found at active enhancers in endometrial cancer cells as marked by the presence of RNA polymerase II and the histone marker H3K27Ac. These ERα binding sites were highly conserved between breast and endometrial cancer and enriched in binding motifs for the transcription factor FOXA1, which displayed substantial overlap with ERα binding sites proximal to genes involved in classical ERα target genes. Multifactorial ChIP-seq data integration from the endometrial cancer cell line Ishikawa illustrated a functional genomic network involving ERα and FOXA1 together with the enhancer-enriched transcriptional regulators p300, FOXM1, TEAD4, FNFIC, CEBP8, and TCF12. Immunohistochemical analysis of 230 primary endometrial tumor specimens showed that lack of FOXA1 and ERα expression was associated with a longer interval between breast cancer and the emergence of endometrial cancer, exclusively in tamoxifen-treated patients. Our results define conserved sites for a genomic interplay between FOXA1 and ERα in breast cancer and tamoxifen-associated endometrial cancer. In addition, FOXA1 and ERα are associated with the interval time between breast cancer and endometrial cancer only in tamoxifen-treated breast cancer patients. Cancer Res; 76(13); 3773-84. ©2016 AACR. PMID:27197147

  8. A Multi-Step miRNA-mRNA Regulatory Network Construction Approach Identifies Gene Signatures Associated with Endometrioid Endometrial Carcinoma

    PubMed Central

    Xiong, Hanzhen; Li, Qiulian; Chen, Ruichao; Liu, Shaoyan; Lin, Qiongyan; Xiong, Zhongtang; Jiang, Qingping; Guo, Linlang

    2016-01-01

    We aimed to identify endometrioid endometrial carcinoma (EEC)-related gene signatures using a multi-step miRNA-mRNA regulatory network construction approach. Pathway analysis showed that 61 genes were enriched on many carcinoma-related pathways. Among the 14 highest scoring gene signatures, six genes had been previously shown to be endometrial carcinoma. By qRT-PCR and next generation sequencing, we found that a gene signature (CPEB1) was significantly down-regulated in EEC tissues, which may be caused by hsa-miR-183-5p up-regulation. In addition, our literature surveys suggested that CPEB1 may play an important role in EEC pathogenesis by regulating the EMT/p53 pathway. The miRNA-mRNA network is worthy of further investigation with respect to the regulatory mechanisms of miRNAs in EEC. CPEB1 appeared to be a tumor suppressor in EEC. Our results provided valuable guidance for the functional study at the cellular level, as well as the EEC mouse models. PMID:27271671

  9. MicroRNA-340 Inhibits Tumor Cell Proliferation and Induces Apoptosis in Endometrial Carcinoma Cell Line RL 95-2.

    PubMed

    Xie, Wei; Qin, Wen; Kang, Yalin; Zhou, Ziyan; Qin, Aiping

    2016-01-01

    BACKGROUND The purpose of our study was to investigate the functional role of microRNA-340 (miR-340) in endometrial carcinoma (EC). MATERIAL AND METHODS Human EC cell line RL 95-2 was transfected with miR-340 mimics, inhibitors, or controls. After 48 h of transfection, the cell viability was determined by 3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl -2-H-tetrazolium bromide (MTT) assay. The BrdU assay and apoptosis assay were performed to determine the effects of miR-340 mimics or inhibitors on cell proliferation and apoptosis, respectively. The underlying mechanisms involved in cell proliferation and apoptosis were explored by measuring the protein levels of cell cycle regulators (p27 kinase inhibition protein (KIP) 1 and p21) and apoptosis-related factors (B-cell lymphoma-2 (Bcl-2), Bax, pro-Caspase 3, and active-Caspase-3). RESULTS Overexpression of miR-340 significantly inhibited the cell viability (P<0.05) and cell proliferation (P<0.01) of RL 95-2 cells compared with the control group, but increased the apoptosis (P<0.01). However, suppression of miR-340 had opposite results. Moreover, the protein levels of p27 KIP1, Bax, pro-Caspase 3, and active-Caspase-3 were significantly increased by overexpression of miR-340 but were statistically decreased by suppression of miR-340. Contrary results were found in the protein levels of Bcl-2. However, no significant differences were found in p21 expression. CONCLUSIONS MiRNA-340 acts as an anti-oncogene in EC cell line RL 95-2 by inhibition of tumor cell proliferation and induction of apoptosis. PMID:27153225

  10. MicroRNA-340 Inhibits Tumor Cell Proliferation and Induces Apoptosis in Endometrial Carcinoma Cell Line RL 95-2

    PubMed Central

    Xie, Wei; Qin, Wen; Kang, Yalin; Zhou, Ziyan; Qin, Aiping

    2016-01-01

    Background The purpose of our study was to investigate the functional role of microRNA-340 (miR-340) in endometrial carcinoma (EC). Material/Methods Human EC cell line RL 95-2 was transfected with miR-340 mimics, inhibitors, or controls. After 48 h of transfection, the cell viability was determined by 3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl -2-H-tetrazolium bromide (MTT) assay. The BrdU assay and apoptosis assay were performed to determine the effects of miR-340 mimics or inhibitors on cell proliferation and apoptosis, respectively. The underlying mechanisms involved in cell proliferation and apoptosis were explored by measuring the protein levels of cell cycle regulators (p27 kinase inhibition protein (KIP) 1 and p21) and apoptosis-related factors (B-cell lymphoma-2 (Bcl-2), Bax, pro-Caspase 3, and active-Caspase-3). Results Overexpression of miR-340 significantly inhibited the cell viability (P<0.05) and cell proliferation (P<0.01) of RL 95-2 cells compared with the control group, but increased the apoptosis (P<0.01). However, suppression of miR-340 had opposite results. Moreover, the protein levels of p27 KIP1, Bax, pro-Caspase 3, and active-Caspase-3 were significantly increased by overexpression of miR-340 but were statistically decreased by suppression of miR-340. Contrary results were found in the protein levels of Bcl-2. However, no significant differences were found in p21 expression. Conclusions MiRNA-340 acts as an anti-oncogene in EC cell line RL 95-2 by inhibition of tumor cell proliferation and induction of apoptosis. PMID:27153225

  11. Endometrial Endometrioid Carcinoma Metastases Show Decreased ER-Alpha and PR-A Expression Compared to Matched Primary Tumors

    PubMed Central

    Bartosch, Carla; Monteiro-Reis, Sara; Vieira, Renata; Pereira, Armindo; Rodrigues, Marta; Jerónimo, Carmen; Lopes, José M.

    2015-01-01

    Patients with endometrial endometrioid carcinoma (EEC) that present with advanced primary disease and develop recurrences have a poor outcome. The phenotype of EEC metastases and recurrences is poorly studied. We evaluated the morphological features and ER-alpha/PRA/p53 immunohistochemical expression of a sample of 45 EEC metastases compared to matched primary tumors. Additionally, we studied methylation levels of ER-alpha/PRA gene promoters. The distribution of histological FIGO grade was significantly different in metastases, which disclosed higher grade than primary tumors (p = 0.005). Mitotic index was significantly lower in metastases compared to matched primary tumors (p<0.001). ER-alpha (p = 0.002) and PRA (p<0.001) median H-scores were significantly lower in metastases than in matched primary EECs, but there was no significant difference concerning p53 expression (p = 0.056). ER-alpha/PRA expression differences did not correlate with differences in metastases morphology. ER-alpha/PRA gene promoter levels were globally low (range: 0% to 11.9%). One case showed higher ER-alpha gene promoter methylation in metastasis compared to matched EEC primary tumor. Regarding PRA, there was a significant higher frequency of its promotor methylation in metastases compared to primary tumors (51.6% vs. 22.7%, p = 0.022). In conclusion, EEC metastatic disease displays phenotypic changes along with ER-alpha and PRA decreased expression compared to primary tumors. ER-alpha and PRA gene promoter methylation seems to play a limited role in the etiology of these alterations. PR expression assessment for hormonal treatment decision of patients with advanced tumors, may be more adequate in metastases than in EEC primary tumors. PMID:26252518

  12. [Endometrial imaging].

    PubMed

    Lemercier, E; Genevois, A; Dacher, J N; Benozio, M; Descargues, G; Marpeau, L

    2000-12-01

    The diagnostic value of endovaginal sonography in benign or malignant endometrial pathology is high, increased by sonohysterography. Sonohysterography is useful in the diagnosis of endometrial thickness and to determine further investigations. MRI is accurate in the uterine adenomyosis diagnosis and is the imaging modality of choice for the preoperative endometrial cancer staging. PMID:11173754

  13. Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

    PubMed Central

    Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

    2015-01-01

    Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with

  14. Hydrosalpinx as a Rare Presentation of Synchronous Ovarian and Endometrial Carcinoma – A Case Report

    PubMed Central

    Khan, Mahjabeen; Amin, Sapna Vinit; Shivananda, Roopa Padavagodu; Patil, Navin

    2016-01-01

    Hydrosalpinx in postmenopausal woman is rare. Most commonly it is due to primary ovarian malignancy with fallopian tube involvement or primary fallopian tube carcinoma. But hydrosalpinx with no malignancy in the fallopian tube, associated with synchronous malignancy of ovary and endometrium is rare. In a postmenopausal women, hydrosalpinx is commonly due to fallopian tube malignancy or rarely pelvic inflammatory disease. We present a rare and very interesting case of 65-year-old nulliparous postmenopausal women with bilateral hydrosalpinx and pyometra who was found to have papillary serous adenocarcinoma of the ovary and endometroid adenocarcinoma of endomertrium with normal fallopian tube. One should always suspect genital malignancy with this presentation, especially in this age group.

  15. Stromal Clues in Endometrial Carcinoma: Loss of Expression of β-Catenin, Epithelial-Mesenchymal Transition Regulators, and Estrogen-Progesterone Receptor

    PubMed Central

    Sayar, Ilyas; Ceyran, Ayse B.; Ibiloglu, Ibrahim; Akalin, Ibrahim; Firat, Ugur; Kosemetin, Duygu; Engin Zerk, Pinar; Aydin, Abdullah

    2016-01-01

    Epithelial-stroma interactions in the endometrium are known to be responsible for physiological functions and emergence of several pathologic lesions. Periglandular stromal cells act on endometrial cells in a paracrine manner through sex hormones. In this study, we immunohistochemically evaluated the expression of epithelial-mesenchymal transition regulators (SNAIL/SLUG, TWIST, ZEB1), adhesion molecules (β-catenin and E-cadhenin), estrogen (ER)-progesterone (PR) receptor and their correlation with each other in 30 benign, 148 hyperplastic (EH), and 101 endometrioid-type endometrial carcinoma (EC) endometria. In the epithelial component, loss of expression in E-cadherin, ER and PR, and overexpression of TWIST and ZEB1 were significantly higher in EC than in EH (P<0.01). In the periglandular stromal component, β-catenin and SNAIL/SLUG expression were significantly higher in normal endometrium and simple without atypical EH compared with complex atypical EH and EC (P<0.01). In addition, periglandular stromal TWIST expression was significantly higher in EH group compared with EC (P<0.05). There was significantly negative correlation between β-catenin and ER, TWIST and ER, and TWIST and PR in hyperplastic and carcinomatous glandular epithelium, whereas there was a significantly positive correlation between β-catenin and SNAIL-SLUG, β-catenin and TWIST, β-catenin and ER, β-catenin and PR, SNAIL-SLUG and ER, SNAIL-SLUG and PR, TWIST and ER, TWIST and PR, in periglandular/cancer-associated stromal cells (P<0.01). In conclusion, the pattern of positive and negative correlations in the expression of epithelial-mesenchymal transition regulators (SNAIL-SLUG and TWIST), sex hormone receptors (ER and PR), and β-catenin between ECs and hyperplasia, as well as between epithelium and stroma herein, is suggestive of a significant role for these proteins and their underlying molecular processes in the development of endometrial carcinomas. PMID:26367784

  16. Stage II endometrial carcinoma treated with external-beam radiotherapy, intracavitary application of cesium, and surgery

    SciTech Connect

    Podczaski, E.S.; Kaminski, P.; Manetta, A.; Louk, D.; Andrews, C.; Larson, J.; DeGeest, K.; Mortel, R. )

    1989-11-01

    From September 1972 to September 1987, thirty-six patients with stage II carcinoma of the endometrium were treated with external-beam radiotherapy to the pelvis, a single intracavitary application of cesium-137, and extrafascial hysterectomy with adnexectomy. Patients were followed for a median of 54.4 months. Overall 2- and 5-year actuarial survival rates were 83 and 58%, respectively. Survival was analyzed in terms of the independent variables surgical stage, presence of a gross cervical lesion, and residual disease within the myometrium or cervix. Factors contributing to patients survival were analyzed by the log-rank method. The 12 patients with a gross cervical lesion had an adverse prognosis, as compared to those without such a lesion (P less than 0.05). Seven of the twelve patients (58%) with a cervical lesion at clinical staging demonstrated persistent or recurrent disease. The presence of extrauterine disease at surgery was a major prognostic factor in patient survival (P less than 0.01). All six patients with extrauterine disease expired 2.3 to 53.0 months after hysterectomy. Two patients with persistence of disease expired 2.3 and 7.5 months after hysterectomy. Eleven patients developed recurrent disease 2.1 to 56.5 months after hysterectomy. All presented with distant metastases. Four of the thirteen patients with persistent or recurrent disease had no residual tumor within the myometrium.

  17. Role of miR-34a as a suppressor of L1CAM in endometrial carcinoma

    PubMed Central

    Schirmer, Uwe; Doberstein, Kai; Rupp, Anne-Kathleen; Bretz, Niko P.; Wuttig, Daniela; Kiefel, Helena; Breunig, Christian; Fiegl, Heidi; Müller-Holzner, Elisabeth; Zeillinger, Robert; Eva, Heidi; Zeimet, Alain G.; SÜltmann, Holger; Altevogt, Peter

    2014-01-01

    L1CAM promotes cell motility, invasion and metastasis formation in various human cancers and can be considered as a driver of tumor progression. Knowledge about genetic processes leading to the presence of L1CAM in cancers is of considerable importance. Experimentally, L1CAM expression can be achieved by various means. Overexpression of the transcription factor SLUG or treatment of cells with TGF-ß1 can induce or augment L1CAM levels in cancer cells. Likewise, hypomethylation of the L1CAM promoter on the X chromosome correlates with L1CAM expression. However, presently no mechanisms that might control transcriptional activity are known. Here we have identified miR-34a as a suppressor of L1CAM. We observed that L1CAM positive endometrial carcinoma (EC) cell lines HEC1B and SPAC1L lost L1CAM protein and mRNA by treatment with demethylating agents or knock-down of the DNA-methyltransferase-1 (DNMT1). Concomitantly, several miRNAs were up-regulated. Using miRNA profiling, luciferase reporter assays and mutagenesis, we identified miR-34a as a putative binder to the L1CAM-3'UTR. Overexpression of miR-34a in HEC1B cells blocked L1CAM expression and inhibited cell migration. In ECC1 cells (wildtype p53) the activation of p53 caused miR-34a up-regulation and loss of L1CAM expression that was miR-34a dependent. We observed an inverse correlation between L1CAM and miR-34a levels in EC cell lines. In primary tumor sections areas expressing high amounts of L1CAM had less miR-34a expression than those with low L1CAM levels. Our data suggest that miR-34a can regulate L1CAM expression by targeting L1CAM mRNA for degradation. These findings shed new light on the complex regulation of L1CAM in human tumors. PMID:24497324

  18. Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  19. Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma

    SciTech Connect

    Niazi, Tamim M.; Souhami, Luis . E-mail: luis.souhami@muhc.mcgill.ca; Portelance, Lorraine; Bahoric, Boris; Gilbert, Lucy; Stanimir, Gerald

    2005-11-15

    Purpose: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy (RT) alone. The goal of this study was to update our experience of high-dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT), for such patients. Methods and Materials: Between 1984 and 2003, 38 patients with Stage I and Stage II adenocarcinoma of the endometrium considered high operative risk received RT as the primary treatment. The median age was 74.1 years. Before 1996, the local extent of the disease was assessed by an examination under anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter. Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy, typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was 42 Gy. Results: At a median follow-up of 57.5 months for patients at risk, 11 patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%) distantly, and 1 patient (3%) locally and distantly. Local failure was established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and higher grade were both associated with increased failure rate. The 15-year disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42% for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade II and III combined (p = 0.0254). Patients with Stage I disease established by MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of 100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3 Grade III or IV. Conclusion: Medically inoperable Stage I endometrial carcinoma may be safely and effectively treated with HDRB as the primary therapy. In selected Stage I patients, our results are

  20. MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC)

    PubMed Central

    Liu, Bo-Liang; Sun, Kai-Xuan; Zong, Zhi-Hong; Chen, Shuo; Zhao, Yang

    2016-01-01

    Here we explore the role of microRNA-372 (miR-372) in tumorigenesis and development of endometrial adenocarcinoma (EC) and analyze the underlying mechanism. We found that miR-372 expression is much lower in EC than normal endometrial specimens. Cell function experiments demonstrated that miR-372 overexpression suppressed cell proliferation, migration, and invasion, and led to a G1 phase arrest and promoted the apoptosis of endometrial carcinoma cells in vitro. The nude mouse xenograft assay demonstrated that miR-372 overexpression suppressed tumor growth. RT-PCR and Western blot assays detected the expression of known targets of miR-372 in other malignant tumors and found Cyclin A1 and Cyclin-dependent Kinase 2 (CDK2) was downregulated by miR-372. Bioinformatic predictions and dual-luciferase reporter assays found that RhoC was a possible target of miR-372. RT-PCR and Western blot assays demonstrated that miR-372 transfection reduced the expression of RhoC, matrix metalloproteinase 2 (MMP2) and MMP9, while it increased the expression of cleaved poly (ADP ribose) polymerase (PARP) and bcl-2-associated X protein (Bax). The cell function experiments that transfected siRNA with RhoC showed the same trend as those which were transfected with miR-372. Taken together, our results demonstrated for the first time that miR-372 suppresses tumorigenesis and the development of EC; RhoC is a new and potentially important therapeutic target. PMID:26673619

  1. Whole Genome Pathway Analysis Identifies an Association of Cadmium Response Gene Loss with Copy Number Variation in Mutant p53 Bearing Uterine Endometrial Carcinomas

    PubMed Central

    Stupack, Dwayne G

    2016-01-01

    Background Massive chromosomal aberrations are a signature of advanced cancer, although the factors promoting the pervasive incidence of these copy number alterations (CNAs) are poorly understood. Gatekeeper mutations, such as p53, contribute to aneuploidy, yet p53 mutant tumors do not always display CNAs. Uterine Corpus Endometrial Carcinoma (UCEC) offers a unique system to begin to evaluate why some cancers acquire high CNAs while others evolve another route to oncogenesis, since about half of p53 mutant UCEC tumors have a relatively flat CNA landscape and half have 20–90% of their genome altered in copy number. Methods We extracted copy number information from 68 UCEC genomes mutant in p53 by the GISTIC2 algorithm. GO term pathway analysis, via GOrilla, was used to identify suppressed pathways. Genes within these pathways were mapped for focal or wide distribution. Deletion hotspots were evaluated for temporal incidence. Results Multiple pathways contributed to the development of pervasive CNAs, including developmental, metabolic, immunological, cell adhesion and cadmium response pathways. Surprisingly, cadmium response pathway genes are predicted as the earliest loss events within these tumors: in particular, the metallothionein genes involved in heavy metal sequestration. Loss of cadmium response genes were associated with copy number changes and poorer prognosis, contrasting with 'copy number flat' tumors which instead exhibited substantive mutation. Conclusion Metallothioneins are lost early in the development of high CNA endometrial cancer, providing a potential mechanism and biological rationale for increased incidence of endometrial cancer with cadmium exposure. Developmental and metabolic pathways are altered later in tumor progression. PMID:27391266

  2. Influence of Cancer-Associated Endometrial Stromal Cells on Hormone-Driven Endometrial Tumor Growth

    PubMed Central

    Pineda, M. J.; Lu, Z.; Cao, D.

    2016-01-01

    Cancer-associated fibroblasts have been shown to inhibit or stimulate tumor growth depending on stage, grade, and tumor type. It remains unclear, however, the effect of endometrial-cancer-associated fibroblasts on hormone-driven responses in endometrial cancer. In this study, we investigated the effect of normal and cancer-associated stromal cells from patients with and without endometrial cancer on endometrial tumor growth in response to estradiol (E2) and progesterone (P4). Compared to benign endometrial stromal cells, the low-grade and high-grade cancer-associated stromal cells exhibited a blunted hormone response for proliferation as well as IGFBP1 secretion. Additional analysis of the influence of stromal cells on hormone-driven tumor growth was done by mixing stromal cells from benign, low-grade, or high-grade tumors, with Ishikawa cells for subcutaneous tumor formation. The presence of both benign and high-grade cancer-associated stromal cells increased estradiol-driven xenografted tumor growth compared to Ishikawa cells alone. Low-grade cancer-associated stromal cells did not significantly influence hormone-regulated tumor growth. Addition of P4 attenuated tumor growth in Ishikawa + benign or high-grade stromal cells, but not in Ishikawa cells alone or with low-grade stromal cells. Using an angiogenesis focused real-time array TGFA, TGFB2 and TGFBR1 and VEGFC were identified as potential candidates for hormone-influenced growth regulation of tumors in the presence of benign and high-grade stromal cells. In summary, endometrial-cancer-associated cells responded differently to in vitro hormone treatment compared to benign endometrial stromal cells. Additionally, presence of stromal cells differentially influenced hormone-driven xenograft growth in vivo depending on the disease status of the stromal cells. PMID:25976290

  3. The immune system during the pre-cancer and the early cancer period. IL-2 production by PBL from post-menopausal women with and without endometrial carcinoma.

    PubMed

    Yron, I; Schickler, M; Fisch, B; Pinkas, H; Ovadia, J; Witz, I P

    1986-09-15

    We report on alterations in IL-2 production and cell proliferation following PHA stimulation of peripheral blood lymphocytes (PBL) from stage-I endometrial carcinoma (EC) patients, and on mechanisms involved in these alterations. Our study includes 3 groups: EC patients, post-menopausal women at high risk of developing EC, and age-matched healthy women. IL-2 production was markedly lower in most EC patients than in healthy controls. Varying levels of IL-2 were produced by PBL from women in the high-risk group. The proliferative response of PBL to PHA appeared to correlate with levels of IL-2 production. Our results suggest that macrophages are involved, in part, in the modulation of T-cell functions of EC patients. PMID:3488968

  4. External Pelvic and Vaginal Irradiation Versus Vaginal Irradiation Alone as Postoperative Therapy in Medium-Risk Endometrial Carcinoma-A Prospective Randomized Study

    SciTech Connect

    Sorbe, Bengt; Horvath, Gyoergy; Andersson, Hakan; Boman, Karin; Lundgren, Caroline; Pettersson, Birgitta

    2012-03-01

    Purpose: To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity. Methods and Materials: Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity. Results: Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-year overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone. Conclusions: Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases.

  5. High-Grading Lunar Samples

    NASA Technical Reports Server (NTRS)

    Allen, Carlton; Sellar, Glenn; Nunez, Jorge; Mosie, Andrea; Schwarz, Carol; Parker, Terry; Winterhalter, Daniel; Farmer, Jack

    2009-01-01

    Astronauts on long-duration lunar missions will need the capability to high-grade their samples to select the highest value samples for transport to Earth and to leave others on the Moon. We are supporting studies to define the necessary and sufficient measurements and techniques for high-grading samples at a lunar outpost. A glovebox, dedicated to testing instruments and techniques for high-grading samples, is in operation at the JSC Lunar Experiment Laboratory. A reference suite of lunar rocks and soils, spanning the full compositional range found in the Apollo collection, is available for testing in this laboratory. Thin sections of these samples are available for direct comparison. The Lunar Sample Compendium, on-line at http://www-curator.jsc.nasa.gov/lunar/compendium.cfm, summarizes previous analyses of these samples. The laboratory, sample suite, and Compendium are available to the lunar research and exploration community. In the first test of possible instruments for lunar sample high-grading, we imaged 18 lunar rocks and four soils from the reference suite using the Multispectral Microscopic Imager (MMI) developed by Arizona State University and JPL (see Farmer et. al. abstract). The MMI is a fixed-focus digital imaging system with a resolution of 62.5 microns/pixel, a field size of 40 x 32 mm, and a depth-of-field of approximately 5 mm. Samples are illuminated sequentially by 21 light emitting diodes in discrete wavelengths spanning the visible to shortwave infrared. Measurements of reflectance standards and background allow calibration to absolute reflectance. ENVI-based software is used to produce spectra for specific minerals as well as multi-spectral images of rock textures.

  6. Gynecologic Cancer InterGroup (GCIG) consensus review for high-grade undifferentiated sarcomas of the uterus.

    PubMed

    Pautier, Patricia; Nam, Eun Ji; Provencher, Diane M; Hamilton, Anne L; Mangili, Giorgia; Siddiqui, Nadeem Ahmad; Westermann, Anneke M; Reed, Nicholas Simon; Harter, Philipp; Ray-Coquard, Isabelle

    2014-11-01

    High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive behavior and poor prognosis. Cyclin D1 has been reported as a diagnostic immunomarker for high-grade endometrial stromal sarcoma with an YWHAE-FAM22 rearrangement. YWHAE-FAM22 endometrial stromal sarcomas (ESS) represent a clinically aggressive subtype of ESS classified as high-grade endometrial sarcomas, and its distinction from the usual low-grade ESS with JAZF1 rearrangement and from HGUS with no identifiable molecular aberration may be important in guiding clinical management. Median age of the patients is between 55 and 60 years. The most common symptoms are vaginal bleeding, abdominal pain, and increasing abdominal girth.Disease is usually advanced with approximately 70% of the patients staged III to IV according to the International Federation of Gynecology and Obstetrics classification. Preferential metastatic locations include peritoneum, lungs, intra-abdominal lymph nodes, and bone. Median progression-free survival ranged from 7 to 10 months, and median overall survival ranged from 11 to 23 months. There is no clear prognostic factor identified for HGUS, not even stage. The standard management for HGUS consists of total hysterectomy and bilateral salpingo-oophorectomy. Systematic lymphadenectomy is not recommended. Adjuvant therapies, such as chemotherapy and radiotherapy, have to be discussed in multidisciplinary staff meetings. PMID:25341584

  7. Endometrial Cancer

    MedlinePlus

    Member Login Join Pay Dues Follow us: Women's Health Care Physicians Contact Us My ACOG ACOG Departments Donate ... and is best made in consultation with your health care team. What happens after treatment for endometrial cancer? ...

  8. Endometrial Cancer

    MedlinePlus

    ... having diabetes. Using estrogen replacement therapy without taking progestin may also increase the risk for endometrial cancer. ... take a combination of estrogen and the hormone progestin. While estrogen stimulates growth of the endometrium, progestin ...

  9. Endometrial Ablation

    MedlinePlus

    ... a thin layer of the lining of the uterus and stops the menstrual flow in many women. ... medical conditions, including the following: • Disorders of the uterus or endometrium • Endometrial hyperplasia • Cancer of the uterus • ...

  10. Endometrial biopsy

    MedlinePlus

    ... Abnormal menstrual periods may be caused by: Uterine fibroids Fingerlike growths in the uterus (uterine polyps) Infection ... More Cancer Endometrial cancer Endometritis Infertility Menopause Uterine fibroids Vaginal bleeding - hormonal Update Date 9/26/2015 ...

  11. Endometrial cancer

    MedlinePlus

    ... endometrial polyps Infrequent periods Never being pregnant Obesity Polycystic ovary syndrome (PCOS) Starting menstruation at an early age (before age ... Epithelium High blood ... Hysterectomy - abdominal - discharge Hysterectomy - laparoscopic - discharge ...

  12. Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-08-15

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  13. The correlation between microRNA490-3p and TGFα in endometrial carcinoma tumorigenesis and progression

    PubMed Central

    Sun, Kai-Xuan; Chen, Ying; Chen, Shuo; Liu, Bo-Liang; Feng, Miao-Xiao; Zong, Zhi-Hong; Zhao, Yang

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3′-untranslated region (3′ UTR). MiR-490-3p has been reported to be a suppressor in various human cancers; however, little is known about the biological functions of miR-490-3p in endometrial cancer (EC). In our study, we found that MiR-490-3p mRNA expression was significantly lower in ECs than in normal endometrial tissues. MiR-490-3p mRNA expression was also negatively associated with depth of invasion (mucosa vs. muscular and serosa) and lymph node metastasis (negative vs. positive) in EC. MiR-490-3p overexpression reduced proliferation; promoted G1 arrest and apoptosis; suppressed migration and invasion; and reduced TGFα, NF-kB, cyclin D1, survivin, matrix metalloproteinase 2 (MMP2) mRNA and protein expression, and improved Bax mRNA and protein expression. The dual-luciferase reporter assay indicated that miR-490-3p directly targeted TGFα by binding its 3′ untranslated region. MiR-490-3P transfection also suppressed tumor development and TGFα expression (as determined by immunohistochemistry and western blotting) in vivo in the xenograft mouse model. This is the first demonstration that miR-490-3P might act as a suppressor in EC tumorigenesis and progression by targeting TGFα. Our results provide a theoretical basis for the further study on the molecular target for endometrial cancer. PMID:26843615

  14. A dual PI3K/AKT/mTOR signaling inhibitor miR-99a suppresses endometrial carcinoma

    PubMed Central

    Li, Yunyun; Zhang, Zhongzu; Zhang, Xiaojing; Lin, Ying; Luo, Tangshu; Xiao, Zhenghua; Zhou, Qin

    2016-01-01

    Activation of the PI3K/AKT/mTOR signaling pathway, a common mechanism in all subtypes of endometrial cancers (EC), plays an important role in the initiation and progression of many cancers. Inhibitors against various components of this pathway might promise a novel effective approach for targeted therapy for EC in the future. Intriguingly, two major members of this pathway, AKT1 and mTOR, were both reported to be the putative target genes of miR-99a, which were widely reported to function as a tumor suppressor in a variety of cancers. However, the direct role of miR-99a in endometrial cancer progression and the signaling pathways might been involved have never been deciphered. In this paper, we demonstrate that the expression of miR-99a was significantly suppressed in the EC tissues and was negatively correlated with the differentiation of tumors. Furthermore, we find that overexpression of miR-99a in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, suppression of cell invasion, and inhibition of tumor growth in vivo, which was mediated, at least partially, through dual-suppression of PI3K/AKT/mTOR pathway. This finding not only helps us understand the molecular mechanism of endometrial carcinogenesis, but also gives us a strong rationale to further investigate miR-99a as a potential biomarker and therapeutic target for EC. PMID:27158364

  15. S100A1 Expression in Ovarian and Endometrial Endometrioid Carcinomas Is a Prognostic Indicator of Relapse-Free Survival

    PubMed Central

    DeRycke, Melissa S.; Andersen, John D.; Harrington, Katherine M.; Pambuccian, Stefan E.; Kalloger, Steve E.; Boylan, Kristin L.M.; Argenta, Peter A.; Skubitz, Amy P.N.

    2011-01-01

    We sought to investigate the expression levels of S100A1 in ovarian cancer cell lines and tissues to correlate S100A1 with subtype, stage, grade, and relapse-free survival. S100A1 messenger RNA and protein were up-regulated in ovarian cancer cell lines and tumors compared with normal ovarian cell lines and tissues by gene microarray analysis, reverse transcriptase–polymerase chain reaction, quantitative reverse transcriptase–polymerase chain reaction, and Western immunoblotting. In the study, 63.7% of serous, 21.2% of clear cell, 11.2% of endometrioid, and 3% of mucinous ovarian (1/31) cancers were S100A1+ by immunohistochemical staining of tissue microarrays (n = 500). S100A1 expression increased with increasing Silverberg grade but not stage in serous tumors. Endometrial tissue microarrays (n = 127) were 9.4% S100A1+; no correlation with stage or grade and S100A1 was found. In the endometrioid subtype of ovarian and endometrial cancers, relapse-free survival was decreased for patients with S100A1+ tumors. These data suggest that S100A1 is a marker for poor prognosis of endometrioid subtypes of cancer. PMID:19926575

  16. miR-200a/miR-141 and miR-205 upregulation might be associated with hormone receptor status and prognosis in endometrial carcinomas

    PubMed Central

    Dong, Ying; Si, Jing-Wen; Li, Wen-Ting; Liang, Li; Zhao, Jian; Zhou, Mei; Li, Dong; Li, Ting

    2015-01-01

    The aim of this study was to compare the clinicopathological significance of miR-200a/miR-141 and miR-205 expression in endometrioid carcinomas (ECs) versus nonendometrioid carcinomas (NECs) and to assess their correlation with hormone receptor status. miR-200a/miR-141 and miR-205 expression in 154 endometrial cancers was determined by qRT-PCR. The status of estrogen and progesterone receptor (ER/PR) was assessed using immunohistochemistry. miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. The expression level of miR-200a was significantly higher in NECs than in ECs (P = 0.025). Furthermore, there was a trend that NECs with worse clinicopathological variables had a higher miR-200a expression, while an inverse trend existed in ECs. miR-205 upregulation occurred frequently in NECs without lymph node metastases (P = 0.030), whereas such association was not present in ECs. Interestingly, In ECs, miR-200a/miR-141 upregulation occurred frequently in the hormone receptor positive subgroups than the negative subgroups (P < 0.05). Similarly, the expression level of miR-205 was higher in the hormone receptor positive subgroups and the association between miR-205 and PR reached statistical significance (P = 0.024). In contrast, in NECs, a negative correlation was found between miR-200a/miR-141 and ER or PR status. Meanwhile, in ECs, miR-200a upregulation correlated with prolonged survival in the ER positive subgroup (P = 0.046), whereas an inverse trend existed in the ER negative subgroup. Our findings suggest that miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. However, they might behave differently in ECs versus NECs. miR-200a/miR-141 and miR-205 might be associated with hormone receptor status in endometrial cancer and may possess prognostic impacts. PMID:26045795

  17. Discovery and validation of methylation markers for endometrial cancer.

    PubMed

    Wentzensen, Nicolas; Bakkum-Gamez, Jamie N; Killian, J Keith; Sampson, Joshua; Guido, Richard; Glass, Andrew; Adams, Lisa; Luhn, Patricia; Brinton, Louise A; Rush, Brenda; d'Ambrosio, Lori; Gunja, Munira; Yang, Hannah P; Garcia-Closas, Montserrat; Lacey, James V; Lissowska, Jolanta; Podratz, Karl; Meltzer, Paul; Shridhar, Viji; Sherman, Mark E

    2014-10-15

    The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies. We compared DNA methylation values of 1,500 probes representing 807 genes in 148 population-based endometrial carcinoma samples and 23 benign endometrial tissues. Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform. Further replication was conducted in The Cancer Genome Atlas and in prospectively collected endometrial brushings from women with and without endometrial carcinomas. We identified 114 CpG sites showing methylation differences with p values of ≤ 10(-7) between endometrial carcinoma and normal endometrium. Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY and SOX1) were selected for further replication. Age-adjusted odds ratios for endometrial cancer ranged from 3.44 (95%-CI: 1.33-8.91) for ASCL2 to 18.61 (95%-CI: 5.50-62.97) for HTR1B. An area under the curve (AUC) of 0.93 was achieved for discriminating carcinoma from benign endometrium. Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the candidate markers. This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy. PMID:24623538

  18. Novel genetic targets in endometrial cancer

    PubMed Central

    Bell, Daphne W.

    2014-01-01

    Worldwide, ~74,000 women die from endometrial cancer each year. Understanding the somatic genomic alterations that drive endometrial tumorigenesis may provide new opportunities to identify targeted therapies for specific subsets of patients. Since 2012, the use of next generation sequencing to decode the mutational landscape of endometrial tumors has not only confirmed prior knowledge of established genetic targets for serous and endometrioid endometrial carcinomas, but has also uncovered novel significantly mutated genes, referred to herein as novel genetic targets, which represent candidate cancer genes in these tumors. This editorial summarizes the novel genetic targets that have been identified in serous and endometrioid ECs, according to their unifying functional characteristics. An expert opinion section comments on remaining knowledge gaps that will undoubtedly be filled in future genomic studies of endometrial cancer. PMID:24750045

  19. The Kruppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Krüppel-like factor 9 (KLF9) is a transcriptional regulator of uterine endometrial cell proliferation, adhesion and differentiation; processes essential for pregnancy success and which are subverted during tumorigenesis. The network of endometrial genes controlled by KLF9 is largely unknown. Over-...

  20. Significance of TGFBR3 allelic loss in the deregulation of TGFβ signaling in primary human endometrial carcinomas.

    PubMed

    Zakrzewski, Piotr K; Nowacka-Zawisza, Maria; Semczuk, Andrzej; Rechberger, Tomasz; Gałczyński, Krzysztof; Krajewska, Wanda M

    2016-02-01

    Downregulation of betaglycan (β-glycan) [transforming growth factor β receptor type III (TGFβR3)], which belongs to co-receptors of the TGFβ pathway, occurs in a broad spectrum of primary human malignancies. However, in the case of endometrial cancer (EC), the mechanisms responsible for genetic alterations are still unknown. Therefore, we investigated allelic imbalance at the TGFBR3 locus (1p33‑p32) in the context of β-glycan mRNA and protein expression, as a possible genetic event determining β-glycan deregulation in EC patients. Study of β-glycan allelic imbalance in 48 primary human ECs was performed with the use of three different microsatellite markers, spanned within or in direct proximity to the TGFBR3 locus. Real‑time PCR and western blotting were used for β-glycan mRNA and protein quantification methods, respectively. Altogether, 25 of 39 (64%) informative cases and 25 of 48 (52%) of all specimens showed allelic imbalance in at least one microsatellite marker, concomitantly with decrease at both the β-glycan transcript and protein levels. Interestingly, 54% (15/28), 36% (8/22) and 35% (7/20) of informative ECs displayed allelic loss in D1S188, D1S435 and D1S1588 microsatellite markers, respectively. It is worth pointing out that 5 out of 39 (13%) informative cases showed loss of heterozygosity (LOH) at two microsatellite markers. Microsatellite instability (MSI) was found in two markers, but to a very strictly limited extent. None of the clinicoprognostic features was found to be of significance. Our results suggest that LOH in the TGFBR3 locus may be one of the mechanisms responsible for loss of β-glycan expression. No correlation of LOH at the TGFBR3 locus with clinicopathological parameters suggests that allelic imbalance may be an early genetic event during neoplastic transformation of human endometrium. PMID:26548418

  1. RNA interference-mediated targeting of DKK1 gene expression in Ishikawa endometrial carcinoma cells causes increased tumor cell invasion and migration

    PubMed Central

    YI, NUO; LIAO, QIN-PING; LI, ZHEN-HUA; XIE, BAO-JIANG; HU, YU-HONG; YI, WEI; LIU, MIN

    2013-01-01

    The Wnt signaling pathway plays an essential role in tumor invasion and migration. DKK1 functions as an important inhibitor of the pathway and represents a promising target for cancer therapy. The aim of the present study was to determine the role of DKK1 in endometrial carcinoma (EC) cell invasion and migration using RNA interference (RNAi) technology. Ishikawa EC cells were transfected at high efficiency with specific DKK1 siRNA. RT-PCR and western blot analysis were used to determine the mRNA and protein levels of DKK1, β-catenin and metalloproteinase 14 (MMP14) in siRNA-treated and -untreated cells. In addition, the invasion and migration of the EC cells were detected by invasion and migration assays. Transient transfection of DKK1 siRNA significantly inhibited the mRNA and protein levels of DKK1. Markedly increased cell invasion and migration was observed following treatment with DKK1 siRNA when compared with the negative control siRNA-treated and siRNA-untreated cells. The knockdown of DKK1 also elevated the mRNA and protein levels of β-catenin and MMP14 involved in the Wnt signaling pathway, indicating that targeting this gene may promote intracellular Wnt signal transduction and thus, accelerate EC cell invasion and migration in vitro. The RNAi-mediated targeting of DKK1 gene expression in Ishikawa EC cells resulted in increased tumor cell invasion and migration. DKK1 was identified as an inhibitor of EC cell invasion and migration via its novel role in the Wnt signaling pathway. Targeting DKK1 may therefore represent an effective anti-invasion and -migration strategy for the treatment of EC. PMID:24137406

  2. Overexpression of claudin-4 may be involved in endometrial tumorigenesis

    PubMed Central

    PAN, XIAO-YU; LI, XUE; CHE, YAN-CI; LI, HONG-YAN; LI, XIN; ZHANG, YUN; YANG, XIN

    2013-01-01

    To clarify the role of claudin-4 in endometrial tumorigenesis and to explore whether claudin-4 could be a potentially useful agent in the treatment of endometrial carcinoma, the expression of claudin-4 in endometrial carcinoma was investigated. The relationship between therapy with anti-neoplastic agents and the expression of claudin-4 was also analyzed using an endometrial carcinoma xenograft model. The expression of claudin-4 in endometrial endometrioid adenocarcinoma (EEC) and normal human endometrial tissue was determined using immunohistochemistry and real-time PCR. Ninety female BALB/c nu/nu mice were transplanted with Ishikawa endometrial cancer cells. The mice were divided into three groups with different intraperitoneal treatments: cisplatin, paclitaxel or saline solution. After the observation period tumors were extracted and stained with monoclonal antibody against claudin-4. The mRNA expression of claudin-4 was also detected using real-time PCR. Expression of claudin-4 was significantly increased at both protein and mRNA levels in the EEC group compared with the group of normal cyclic endometrium. In the study of Ishikawa xenografts, no significant changes in tumor volume and claudin-4 expression were shown in the paclitaxel group compared with the control group. A significant reduction of tumor growth and a significant decrease in claudin-4 expression were observed in the cisplatin group. These results demonstrate that claudin-4 is strongly expressed in EEC. Claudin-4 is a useful biomarker in the treatment of patients with endometrial carcinoma. PMID:23599806

  3. Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery.

    PubMed

    Rabban, Joseph T; Garg, Karuna; Crawford, Beth; Chen, Lee-may; Zaloudek, Charles J

    2014-06-01

    Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined

  4. Three or Four Fractions of 4-5 Gy per Week in Postoperative High-Dose-Rate Brachytherapy for Endometrial Carcinoma

    SciTech Connect

    Rovirosa, Angeles; Ascaso, Carlos; Sanchez-Reyes, Alberto; Herreros, Antonio; Abellana, Rosa; Pahisa, Jaume; Lejarcegui, Jose Antonio; Biete, Albert

    2011-10-01

    Purpose: To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a schedule of three or four fractions per week, when possible, in 89 patients on local control and toxicity in postoperative treatment of endometrial carcinoma. The effect of the overall HDRBT treatment time (OTT) on toxicity was also evaluated. Patients and Methods: Federation Internationale de Gynecologie Obstetrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC. Radiotherapy: Group 1-67 of 89 patients received external beam irradiation (EBI; 44-50 Gy) plus HDRBT (3 fractions of 4-6 Gy); Group 2-22 of 89 patients received HDRBT alone (6 fractions of 4-5 Gy). OTT: Group 1-HDRBT was completed in a median of 5 days in 32 patients and in >5 days in 35; Group 2-HDRBT was completed in <15 days in 11 patients and in {>=}16 days in 11. Toxicity was evaluated using Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study was performed in vaginal mucosa surface. Statistics included Student's t test, chi-square test, and receiving operator curves. Results: With a mean follow-up of 31 months (range, 6-70), 1 of 89 patients had vaginal relapse. Early toxicity appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in 13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade 2; rectal three Grade 1, one Grade 2. No differences were found in relation to OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2. Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in Group 2. Conclusions: Three fractions of 4-5 Gy in 3-5 days after EBI or 6 fractions in <15 days in patients receiving HDRBT alone was a safe treatment in relation to toxicity and local control. Vaginal surface BED less than 75 Gy after EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity.

  5. Prognostic implications of epithelial to mesenchymal transition related proteins (E-cadherin, Snail) and hypoxia inducible factor 1α in endometrioid endometrial carcinoma.

    PubMed

    Abouhashem, Nehal S; Ibrahim, Doaa Abdelaziz; Mohamed, Abdel Motaleb

    2016-06-01

    The epithelial-mesenchymal transition (EMT) is an important step in the invasion and metastasis of cancer. E-cadherin downregulation, which is essentially controlled by EMT-mediated proteins such as Snail, is a main molecular feature of this process. Tumor hypoxia is one of the essential biological phenomena that are associated with the development and progression of various solid tumors. Recently, hypoxia and hypoxia-inducible factor 1α (HIF-1α) signaling pathway were identified to have an essential role in the regulation of EMT phenotype. The aim of the study was to evaluate the prognostic impact of EMT-related proteins (E-cadherin, Snail) and HIF-1α in endometrioid endometrial carcinoma (EEC) among Egyptian women. Immunohistochemical evaluation of E-cadherin, Snail, and HIF-1α expression was performed using 50 cases of EEC. The relationship between protein expression and clinicopathological features was investigated. The frequency of immunopositivity for E-cadherin, Snail, and HIF-1α in our cases of EEC was 82%, 28%, and 66%, respectively. Reduced E-cadherin and increased nuclear expression of Snail as well as HIF-1α were significantly associated with histopathologic grade, clinical stage myometrial invasion, and lymph node involvement. Statistical analysis showed a positive correlation between HIF-1α overexpression and Snail upregulation (τ= +0.252, P= .025); however, E-cadherin expression level was inversely correlated with enhanced Snail expression (τ= -0.450, P< .001) as well as with HIF-1α overexpression (τ= -0.439, P< .001). The overall survival and progression-free survival were inversely related to Snail immunoreactivity and positively related to E-cadherin expression. E-cadherin and Snail have a predictive value in EEC. In conclusion, the current study reveals that both Snail and HIF-1α expressions are significantly associated with poor prognosis in EEC; however, E-cadherin expression is considered a marker of good prognosis. E-cadherin and

  6. Pilot study in the treatment of endometrial carcinoma with 3D image-based high-dose-rate brachytherapy using modified Heyman packing: Clinical experience and dose-volume histogram analysis

    SciTech Connect

    Weitmann, Hajo Dirk . E-mail: dirk.weitmann@akhwien.at; Poetter, Richard; Waldhaeusl, Claudia; Nechvile, Elisabeth; Kirisits, Christian; Knocke, Tomas Hendrik

    2005-06-01

    Purpose: The aim of this study was to evaluate dose distribution within uterus (clinical target volume [CTV]) and tumor (gross tumor volume [GTV]) and the resulting clinical outcome based on systematic three-dimensional treatment planning with dose-volume adaptation. Dose-volume assessment and adaptation in organs at risk and its impact on side effects were investigated in parallel. Methods and Materials: Sixteen patients with either locally confined endometrial carcinoma (n = 15) or adenocarcinoma of uterus and ovaries after bilateral salpingo-oophorectomy (n = 1) were included. Heyman packing was performed with mean 11 Norman-Simon applicators (3-18). Three-dimensional treatment planning based on computed tomography (n = 29) or magnetic resonance imaging (n = 18) was done in all patients with contouring of CTV, GTV, and organs at risk. Dose-volume adaptation was achieved by dwell location and time variation (intensity modulation). Twelve patients treated with curative intent received five to seven fractions of high-dose-rate brachytherapy (7 Gy per fraction) corresponding to a total dose of 60 Gy (2 Gy per fraction and {alpha}/{beta} of 10 Gy) to the CTV. Four patients had additional external beam radiotherapy (range, 10-40 Gy). One patient had salvage brachytherapy and 3 patients were treated with palliative intent. A dose-volume histogram analysis was performed in all patients. On average, 68% of the CTV and 92% of the GTV were encompassed by the 60 Gy reference volume. Median minimum dose to 90% of CTV and GTV (D90) was 35.3 Gy and 74 Gy, respectively. Results: All patients treated with curative intent had complete remission (12/12). After a median follow-up of 47 months, 5 patients are alive without tumor. Seven patients died without tumor from intercurrent disease after median 22 months. The patient with salvage treatment had a second local recurrence after 27 months and died of endometrial carcinoma after 57 months. In patients treated with palliative

  7. What Is Endometrial Cancer?

    MedlinePlus

    ... endometrial adenocarcinomas. These types tend to be more aggressive than most endometrial cancers. They tend to grow ... forming glands. Grade 3 cancers tend to be aggressive and have a poorer outlook than lower-grade ...

  8. Clinical and pathological correlations in endometrial pathology

    PubMed Central

    Bohîlțea, RE; Sajin, M; Furtunescu, F; Bohîlțea, LC; Mihart, A; Baros, A; Anca, AF

    2015-01-01

    The incidence and mortality rate of endometrial cancer has been registering an increasing trend both in Romania and in the whole world. The paper’s aim is to analyze the diagnostic approach of endometrial pathology in the University Emergency Hospital Bucharest, on a four years period. The medium age of the patients was of 50.51 ± 10.924 years, and the median age was of 48 years. The youngest patient suffering from endometrial cancer was of 30 years. Dilation and uterine curettage represent the main method used in the performance of endometrial biopsy, based on which the certitude etiologic histopathologic diagnosis was established in 68.4% of the patients with endometrial pathology. Hyperplasias represented half of the pathology (54.9%), most of them being without atypias. Endometrial carcinoma was identified in 19% of the patients. The diagnosis of the disease in IA stage represents 5.5% of the total endometrial cases and the diagnosis of the disease in the stage of its limitation to the uterus (stage IA, IB and IC) was of 64.2%. The endometrioid adenocarcinoma represents the most encountered histopathological form and the degree of tumor differentiation established for 68,15% of the cases was predominantly 1 and 2 (88%). The main symptom, which determines the patients’ decision to go to the physician, is the abnormal uterine bleeding. 66% of the cases of endometrial cancer in the stage of the disease limited to the uterus are diagnosed in Romania based on the abnormal uterine bleeding. However, 34% of the cases are diagnosed in advanced stages, presenting a significantly low life expectancy. PMID:26664489

  9. Endometrial cancer.

    PubMed

    Morice, Philippe; Leary, Alexandra; Creutzberg, Carien; Abu-Rustum, Nadeem; Darai, Emile

    2016-03-12

    Endometrial cancer is the most common gynaecological tumour in developed countries, and its incidence is increasing. The most frequently occurring histological subtype is endometrioid adenocarcinoma. Patients are often diagnosed when the disease is still confined to the uterus. Standard treatment consists of primary hysterectomy and bilateral salpingo-oophorectomy, often using minimally invasive approaches (laparoscopic or robotic). Lymph node surgical strategy is contingent on histological factors (subtype, tumour grade, involvement of lymphovascular space), disease stage (including myometrial invasion), patients' characteristics (age and comorbidities), and national and international guidelines. Adjuvant treatment is tailored according to histology and stage. Various classifications are used to assess the risks of recurrence and to determine optimum postoperative management. 5 year overall survival ranges from 74% to 91% in patients without metastatic disease. Trials are ongoing in patients at high risk of recurrence (including chemotherapy, chemoradiation therapy, and molecular targeted therapies) to assess the modalities that best balance optimisation of survival with the lowest adverse effects on quality of life. PMID:26354523

  10. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  11. Adjuvant progestagens for endometrial cancer

    PubMed Central

    Martin-Hirsch, Pierre PL; Bryant, Andrew; Keep, Sarah L; Kitchener, Henry C; Lilford, Richard

    2014-01-01

    Background Endometrial cancer is the most common genital tract carcinoma among women in developed countries, with most women presenting with stage 1 disease. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease. Objectives To evaluate the effectiveness and safety of adjuvant progestagen therapy for the treatment of endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Specilaised Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. MEDLINE and EMBASE up to April 2009. Selection criteria Randomised controlled trials (RCTs) of progestagen therapy in women who have had surgery for endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Risk ratios (RRs) comparing survival in women who did and did not receive progestagen were pooled in random effects meta-analyses.. Main results Seven trials assessing 4556 women were identified. Three trials included women with stage one disease only, whereas four included women with more advanced disease. Meta-analysis of four trials showed that there was no significant difference in the risk of death at five years between adjuvant progestagen therapy and no further treatment (RR = 1.00, 95% CI 0.85 to 1.18). This conclusion is also robust to single trial analyses at 4 and 7 years and in one trial across all points in time using a hazard ratio (HR). There was also no significant difference between progestagen therapy and control in terms of the risk of death from endometrial cancer, cardiovascular disease and intercurrent disease. Relapse of disease appeared to be reduced by progestagen therapy in one trial (HR = 0.71, 95% CI 0.52 to 0.97 and 5 year RR = 0.74, 95% CI 0.58 to 0.96), but there was no evidence of a difference in disease recurrence in another trial at 7 years (RR = 1.34, 95% CI 0.79 to 2.27). Authors’ conclusions There

  12. Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-08-02

    Endometrial Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC1 Uterine Corpus Cancer; Stage IIIC2 Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  13. Incidental Serous Tubal Intraepithelial Carcinoma and Non-Neoplastic Conditions of the Fallopian Tubes in Grossly Normal Adnexa: A Clinicopathologic Study of 388 Completely Embedded Cases.

    PubMed

    Seidman, Jeffrey D; Krishnan, Jayashree; Yemelyanova, Anna; Vang, Russell

    2016-09-01

    Serous tubal intraepithelial carcinoma (STIC), the putative precursor of the majority of extrauterine high-grade serous carcinomas, has been reported in both high-risk women (those with a germline BRCA mutation, a personal history of breast carcinoma, and/or family history of breast or ovarian carcinoma) and average risk women from the general population. We reviewed grossly normal adnexal specimens from 388 consecutive, unselected women undergoing surgery, including those with germline BRCA mutation (37 patients), personal history of breast cancer or family history of breast/ovarian cancer (74 patients), endometrial cancer (175 patients), and a variety of other conditions (102 patients). Among 111 high-risk cases and 277 non-high-risk cases, 3 STICs were identified (0.8%), all in non-high-risk women (high risk vs. non-high risk: P=not significant). STIC was found in 2 women with nonserous endometrial carcinoma and 1 with complex atypical endometrial hyperplasia. Salpingoliths (mucosal calcifications), found in 9% of high-risk cases, and fimbrial adenofibromas in 9.9% of high-risk cases, were significantly more common in high-risk as compared with non-high-risk women (1.8% and 2.5%, respectively; P<0.007). Mucinous metaplasia was found in 3.1%, salpingitis isthmica nodosa in 3.4%, hemosiderin or pseudoxanthoma cells in 4.9%, and fibrous luminal nodules in 4.1%. None of these latter features differed significantly in the high-risk versus non-high-risk groups. These findings suggest a possible association between STIC and endometrial hyperplasia and carcinoma, and clarify the frequency of non-neoplastic tubal findings in grossly normal fallopian tubes. PMID:26630221

  14. Metformin for endometrial hyperplasia: a Cochrane protocol

    PubMed Central

    Clement, Naomi S; Oliver, Thomas R W; Shiwani, Hunain; Saner, Juliane R F; Mulvaney, Caroline A; Atiomo, William

    2016-01-01

    Introduction Endometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this. Methods and analysis We will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments. Ethics and dissemination

  15. Quantitative PCR marker genes for endometrial adenocarcinoma.

    PubMed

    Kölbl, Alexandra C; Victor, Lisa-Marie; Birk, Amelie E; Jeschke, Udo; Andergassen, Ulrich

    2016-09-01

    Endometrial adenocarcinoma is a common malignancy in women worldwide, with formation of remote metastasis occurring following oncological treatment. Circulating tumor cells (CTCs) are regarded to be the origin of haematogenous metastasis formation. The present study aimed to identify suitable marker genes using a quantitative polymerase chain reaction (qPCR) approach to detect CTCs from blood samples of patients with endometrial carcinoma. Therefore, RNA was isolated from endometrial adenocarcinoma cell lines and from healthy endometrial tissue and reverse transcribed to cDNA, which was then used in qPCR on a number of marker genes. Cytokeratin 19 and claudin 4 were identified as suitable marker genes for CTCs in endometrial adenocarcinoma, due to their high expression in the majority of the cell lines investigated. The expression values of the genes examined varied widely between the different cell lines, which is similar to the variation in the patient samples. Therefore, the necessity for a set of genes for CTC detection and not one single marker gene is demonstrated. qPCR is a fast, cost‑efficient and easy to perform technique, which may be used in the detection of CTCs. Investigation of the occurrence of CTCs in cancer patients would aid in the prevention of metastasis and thereby refine treatment. PMID:27431566

  16. High grade neuroendocrine neoplasm of the antrum and orbit.

    PubMed

    MacIntosh, Peter W; Jakobiec, Frederick A; Stagner, Anna M; Gilani, Sapideh; Fay, Aaron

    2015-01-01

    Neuroendocrine malignancies-tumors characterized by the production of dense-core secretory granules-are most often encountered in the lungs and can also be found in extrapulmonary sites. Our patient had a primary neuroendocrine tumor of the antrum with an elusive cell of origin that secondarily invaded the inferior orbit. In the sinuses, neuroendocrine tumors may be confused with infectious sinusitis or squamous cell carcinoma. There are no known pathognomonic clinical or radiographic signs to distinguish these tumors from other conditions. Diagnosis depends on a biopsy with histopathologic and immunohistochemical analysis to identify biomarkers such as synaptophysin, chromogranin, CD56 and neuron specific enolase. Our patient's tumor defied precise immunohistochemical characterization because of its primitive character and erratic biomarker expression. The diagnosis oscillated between a neuroendocrine carcinoma and an ectopic esthesioneuroblastoma grade IV-hence the use of the more generic nosologic category of neuroendocrine neoplasm without specifying a neuronal or epithelial origin. Data to guide management are limited, particularly in the ophthalmic literature, and derive from experience with tumors of the sinonasal compartments. In the present case of a sino-orbital high grade neuroendocrine neoplasm, regional lymph node metastases developed shortly after presentation. The tumor has responded well to chemotherapy and radiation, but recurrence is often encountered within 2 years in this class of neoplasms. PMID:26077631

  17. Gene therapy for high-grade glioma

    PubMed Central

    Natsume, Atsushi

    2008-01-01

    The treatment of high-grade gliomas remains difficult despite recent advances in surgery, radiotherapy and chemotherapy. True advances may emerge from the increasing understanding in molecular biology and discovery of novel mechanisms for the delivery of tumoricidal agents. In an attempt to overcome this formidable neoplasm, molecular approaches using gene therapy have been investigated clinically since 1992. The clinical trials have mainly been classified into three approaches: suicide gene therapy, immune gene therapy and oncolytic viral therapy. In this article, we review these approaches, which have been studied in previous and ongoing clinical trials. PMID:19262115

  18. Studies on high grade cerebral gliomas

    SciTech Connect

    Bleehen, N.M. )

    1990-04-01

    A brief review of attempts in the United Kingdom to improve the results of treatment of high grade (grade 3, 4) supra-tentorial astrocytomas is presented. The radiosensitizer misonidazole failed to improve the results of post-surgical radiotherapy, however, multivariate analysis of data from these patients has provided a prognostic index of use in defining good and poor prognosis patients. An overview study of adjuvant nitrosourea therapy trials has shown a small significant advantage for the chemotherapy. A study of chemosensitization by benznidazole of CCNU treatment of patients in relapse failed to demonstrate any effect. 13 references.

  19. Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: a bioinformatic and clinical study and the therapeutic implication

    PubMed Central

    He, Shuming; Zeng, Shumei; Zhou, Zhi-Wei; He, Zhi-Xu; Zhou, Shu-Feng

    2015-01-01

    The aberrant expression of human microRNA-181a-1 (hsa-miR-181a) has been implicated in the pathogenesis of various cancers, serving as an oncogene or a tumor suppressor. However, the role of hsa-miR-181a in the pathogenesis of endometrial carcinoma (EC) and its clinical significance are unclear. This study aimed to search for the molecular targets of hsa-miR-181a using bioinformatic tools and then determine the expression levels of hsa-miR-181a in normal, hyperplasia, and EC samples from humans. To predict the targets of hsa-miR-181a, ten different algorithms were used, including miRanda-mirSVR, DIANA microT v5.0, miRDB, RNA22 v2, TargetMiner, TargetScan 6.2, PicTar, MicroCosm Targets v5, and miRWALK. Two algorithms, TarBase 6.0 and miRTarBase, were used to identify the validated targets of hsa-miR-181a-5p (a mature product of hsa-miR-181a), and the web-based Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.7 was used to provide biological functional interpretation of the validated targets of hsa-miR-181a-5p. A total of 78 formalin-fixed, paraffin-embedded tissue specimens from 65 patients and 13 healthy subjects were collected and examined, including normal endometrium (n=13), endometrial hyperplasia (n=18), and EC (37 type I and 10 type II EC cases). Our bioinformatic studies have showed that hsa-miR-181a might regulate a large number of target genes that are important in the regulation of critical cell processes, such as cell fate, cell survival, metabolism, and cell death. To date, 313 targets of hsa-miR-181a have been validated, and 22 of these targets are cancer genes. The precision of predictions by all the algorithms for hsa-miR-181a-1’s targets was low. Many of these genes are involved in tumorigenesis of various cancers, including EC, based on the DAVID and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In comparison with normal endometrial tissue, the expression level of hsa-miR-181a was significantly

  20. Expression of metalloproteinases endometrial stromal sarcoma: immunohistochemical study using image analysis.

    PubMed Central

    Liokumovich, P; Goldberg, I; Davidson, B; Gotlieb, W H; Zahavi, T; Ben-Baruch, G; Reder, I; Kopolovic, J

    1999-01-01

    AIM: To investigate the expression of matrix metalloproteinases (MMP), a group of proteolytic enzymes with a central role in extracellular matrix invasion and degradation, in stromal sarcomas. METHODS: 11 endometrial stromal sarcomas (four low grade tumours, seven high grade) were stained for MMP-2, MMP-3, and MMP-9 using immunohistochemical stains. The surgical material consisted of nine hysterectomy specimens and two pelvic recurrences. Three hysterectomy specimens, removed for leiomyomas, were studied as controls. Staining area was evaluated using image analysis. RESULTS: Age at the time of diagnosis ranged from 21 to 67 years. Four of the 11 patients (three with high grade tumours and one with a low grade tumour) died of the disease, six remained free of disease, and one was lost to follow up. Staining for MMP-2, MMP-3, and MMP-9 was more diffuse in high grade tumours than in low grade tumours and controls. Staining for MMP-3 and MMP-9 was more pronounced in high grade than in low grade tumours (p = 0.04; p = 0.05). Staining for MMP-9 was significantly greater in all stromal sarcomas than in controls (p < 0.001 for high grade tumours v controls; p < 0.01 for low grade tumours v controls). Diffuse staining for MMP-2, exceeding 90% of the tumour area, was observed in three of seven high grade tumours but in no low grade tumours. There was no apparent correlation between staining for any of the three enzymes and survival. CONCLUSIONS: Both low and high grade endometrial stromal tumours express matrix metalloproteinases. MMP-3 and MMP-9 are expressed more diffusely in high grade than in low grade tumours. In the individual case, diffuse staining for MMP-2 appears to best characterise the high grade tumours. Thus staining for MMP-2 may aid in differentiating high grade from low grade tumours, and MMP-9 in differentiating normal endometrial stroma from low and high grade endometrial stromal sarcomas. MMP expression does not appear to predict disease outcome in

  1. [Molecular based targets and endometrial cancer].

    PubMed

    Stoyanov, St; Ananiev, J; Ivanova, K; Velev, V; Todorova, M; Gulubova, M

    2015-01-01

    In recent years, increasing attention has been paid to the rate of spread of endometrial carcinoma, especially in the postmenopausal period. Along with routine diagnostic methods, giving information on the location and progression of the disease, there are some morphological methods determining very accurately the correlations in the development of this type of cancer and his prognosis. Moreover--in recent years, the accumulated information about the molecular profile of this type of cancer made it possible to implement a number of new drugs against the so-called molecular therapy -'targets' in the neoplastic process. Significant proportion of cases show response rates, it is more hope in the development of more successful formulas and target -based therapy. In this review, we present and discuss the role of certain molecular markers as potential indicators of prognosis and development, as well as determining the target treatment of endometrial carcinoma. PMID:25909140

  2. A Phase II Study of Intensity Modulated Radiation Therapy to the Pelvis for Postoperative Patients With Endometrial Carcinoma: Radiation Therapy Oncology Group Trial 0418

    SciTech Connect

    Jhingran, Anuja; Winter, Kathryn; Portelance, Lorraine; Miller, Brigitte; Salehpour, Mohammad; Gaur, Rakesh; Souhami, Luis; Small, William; Berk, Lawrence; Gaffney, David

    2012-09-01

    Purpose: To determine the feasibility of pelvic intensity modulated radiation therapy (IMRT) for patients with endometrial cancer in a multi-institutional setting and to determine whether this treatment is associated with fewer short-term bowel adverse events than standard radiation therapy. Methods: Patients with adenocarcinoma of the endometrium treated with pelvic radiation therapy alone were eligible. Guidelines for target definition and delineation, dose prescription, and dose-volume constraints for the targets and critical normal structures were detailed in the study protocol and a web-based atlas. Results: Fifty-eight patients were accrued by 25 institutions; 43 were eligible for analysis. Forty-two patients (98%) had an acceptable IMRT plan; 1 had an unacceptable variation from the prescribed dose to the nodal planning target volume. The proportions of cases in which doses to critical normal structures exceeded protocol criteria were as follows: bladder, 67%; rectum, 76%; bowel, 17%; and femoral heads, 33%. Twelve patients (28%) developed grade {>=}2 short-term bowel adverse events. Conclusions: Pelvic IMRT for endometrial cancer is feasible across multiple institutions with use of a detailed protocol and centralized quality assurance (QA). For future trials, contouring of vaginal and nodal tissue will need continued monitoring with good QA and better definitions will be needed for organs at risk.

  3. Barrett's esophagus: management of high-grade dysplasia and cancer.

    PubMed

    Ruol, Alberto; Zaninotto, Giovanni; Costantini, Mario; Battaglia, Giorgio; Cagol, Matteo; Alfieri, Rita; Epifani, Magdalena; Ancona, Ermanno

    2004-03-01

    Esophagectomy remains the treatment of choice for the appropriate patient with Barrett's adenocarcinoma invading beyond the mucosa, without evidence of distant metastasis or invasion of adjacent organs. On the other hand, therapeutic management of patients with Barrett's high-grade dysplasia (HGD) or mucosal adenocarcinoma should be individualized, taking into account the patient's preferences, willingness to return for frequent endoscopic biopsies, and medical fitness to undergo esophagectomy. Surgery has to be considered the best treatment for HGD or superficial carcinoma, unless contraindicated by severe comorbidities, because it has proven to be the only treatment that is successful in curing the condition and preventing recurrent HGD or the development of invasive cancer. Nonsurgical treatment by photodynamic therapy or endoscopic mucosal resection may be a less invasive and organ-sparing option for elderly, poor-risk patients but it is still to be considered an investigational therapy that should only be conducted under a clinical trial protocol. Finally, intensive endoscopic biopsy surveillance of patients with HGD is another investigational option that may allow prompt treatment of cancer if it develops. However, few data document the safety of this observational approach. PMID:15013713

  4. Cervical cytology in serous and endometrioid endometrial cancer.

    PubMed

    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

    2013-07-01

    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. PMID:23722512

  5. Evolutionary etiology of high-grade astrocytomas

    PubMed Central

    Song, Yurong; Zhang, Qian; Kutlu, Burak; Difilippantonio, Simone; Bash, Ryan; Gilbert, Debra; Yin, Chaoying; O’Sullivan, T. Norene; Yang, Chunyu; Kozlov, Serguei; Bullitt, Elizabeth; McCarthy, Ken D.; Kafri, Tal; Louis, David N.; Miller, C. Ryan; Hood, Leroy; Van Dyke, Terry

    2013-01-01

    Glioblastoma (GBM), the most common brain malignancy, remains fatal with no effective treatment. Analyses of common aberrations in GBM suggest major regulatory pathways associated with disease etiology. However, 90% of GBMs are diagnosed at an advanced stage (primary GBMs), providing no access to early disease stages for assessing disease progression events. As such, both understanding of disease mechanisms and the development of biomarkers and therapeutics for effective disease management are limited. Here, we describe an adult-inducible astrocyte-specific system in genetically engineered mice that queries causation in disease evolution of regulatory networks perturbed in human GBM. Events yielding disease, both engineered and spontaneous, indicate ordered grade-specific perturbations that yield high-grade astrocytomas (anaplastic astrocytomas and GBMs). Impaired retinoblastoma protein RB tumor suppression yields grade II histopathology. Additional activation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) network drives progression to grade III disease, and further inactivation of phosphatase and tensin homolog (PTEN) yields GBM. Spontaneous missense mutation of tumor suppressor Trp53 arises subsequent to KRAS activation, but before grade III progression. The stochastic appearance of mutations identical to those observed in humans, particularly the same spectrum of p53 amino acid changes, supports the validity of engineered lesions and the ensuing interpretations of etiology. Absence of isocitrate dehydrogenase 1 (IDH1) mutation, asymptomatic low grade disease, and rapid emergence of GBM combined with a mesenchymal transcriptome signature reflect characteristics of primary GBM and provide insight into causal relationships. PMID:24114272

  6. Hormones and endometrial carcinogenesis.

    PubMed

    Kamal, Areege; Tempest, Nicola; Parkes, Christina; Alnafakh, Rafah; Makrydima, Sofia; Adishesh, Meera; Hapangama, Dharani K

    2016-02-01

    Endometrial cancer (EC) is the commonest gynaecological cancer in the Western World with an alarmingly increasing incidence related to longevity and obesity. Ovarian hormones regulate normal human endometrial cell proliferation, regeneration and function therefore are implicated in endometrial carcinogenesis directly or via influencing other hormones and metabolic pathways. Although the role of unopposed oestrogen in the pathogenesis of EC has received considerable attention, the emerging role of other hormones in this process, such as androgens and gonadotropin-releasing hormones (GnRH) is less well recognised. This review aims to consolidate the current knowledge of the involvement of the three main endogenous ovarian hormones (oestrogens, progesterone and androgens) as well as the other hormones in endometrial carcinogenesis, to identify important avenues for future research. PMID:26966933

  7. Endometrial Cancer Risk Factors

    MedlinePlus

    ... Women with a condition called polycystic ovarian syndrome (PCOS) have abnormal hormone levels, such as higher androgen ( ... increase a woman's chance of getting endometrial cancer. PCOS is also a leading cause of infertility in ...

  8. The endometrial hyperplasias revisited.

    PubMed

    Sivridis, Efthimios; Giatromanolaki, Alexandra

    2008-09-01

    The proliferating lesions in the endometrium form a morphological continuum extending from benign to malignant, through a transitional pre-invasive stage. Within this spectrum, several classifications of endometrial hyperplasia have been developed over the years in which the precancerous lesions gained a substantial distinction, although not without inconsistencies in definitions and terminology. The revised WHO 1994 classification explicitly recognizes cytological atypia as the defining feature for distinguishing genuine hyperplastic lesions (simple and complex endometrial hyperplasia) from those that are potentially precancerous (simple and complex atypical endometrial hyperplasia) and puts an end to the verbal anarchy by adopting a common language of communication. This taxonomy, however, was criticized for complexity and low level of reproducibility. Thus, in the name of improved reproducibility a new classification was recently proposed which (a) combines simple and complex endometrial hyperplasia within one diagnostic category known as endometrial hyperplasia and (b) defines new criteria for recognising the precancerous lesions: a monoclonal growth, known as endometrial intraepithelial neoplasia (EIN), comprising clusters of crowded glands, greater than 1 mm in diameter, having a cytologically altered epithelium. The EIN concept was challenged of not being independently tested and received with great enthusiasm by some scholars and relative skepticism by others. PMID:18726114

  9. Endometrial cancer following radiation therapy for cervical cancer

    SciTech Connect

    Gallion, H.H.; van Nagell, J.R. Jr.; Donaldson, E.S.; Powell, D.E.

    1987-05-01

    The clinical and histologic features of eight cases of carcinoma of the endometrium which developed following radiation therapy for squamous cell carcinoma of the cervix are described. No patient had a well-differentiated tumor and significant myometrial invasion was present in all cases. Three of the eight tumors were papillary serous adenocarcinoma. Five of the eight patients developed recurrent tumor and died of their disease. The risk of endometrial cancer in patients previously radiated for cervical cancer is evaluated.

  10. Endometrial cancer: Not your grandmother's cancer.

    PubMed

    McAlpine, Jessica N; Temkin, Sarah M; Mackay, Helen J

    2016-09-15

    Worldwide, the incidence of endometrial carcinoma (EC) is rapidly increasing, and the highest disease burden is reported in North America and Western Europe. Although the prognosis remains good for patients with are diagnosed with early stage EC, for those with recurrent or metastatic disease, the options are few, and the median overall survival is short. It is imperative to gain a greater understanding of all aspects of EC, limit its effect on scarce health care resources and, more importantly, prevent this cancer from significantly impacting future generations of women. An exciting new era of endometrial cancer research and clinical management has begun that incorporates biologically and clinically relevant genomic and clinicopathologic parameters. Continued collaborative research efforts and funding are essential if we are to advance our understanding of this disease and improve clinical outcomes. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2787-2798. © 2016 American Cancer Society. PMID:27308732

  11. MR staging in carcinoma of the endometrium and carcinoma of the cervix.

    PubMed Central

    Pakkal, M. V.; Rudralingam, V.; McCluggage, W. G.; Kelly, B. E.

    2004-01-01

    This study aimed to evaluate MR as an imaging modality for the assessment of myometrial and cervical invasion in endometrial carcinoma and for the assessment of parametrial and lymph node involvement in cervical carcinoma. Twenty-eight patients with a preoperative histological diagnosis of endometrial carcinoma/cervical carcinoma were included in the study. The findings were compared with the surgical staging and the histopathological report of the hysterectomy specimen. Accuracy in detecting myometrial and cervical involvement in patients with endometrial carcinoma was 78% for both. Accuracy in detecting parametrial and lymph node involvement in patients with cervical carcinoma was 71% and 86% respectively. MR is a reliable method for preoperative assessment of endometrial and cervical carcinoma. It helps decide operability, the type of operation and aids in the selection of patients who need to be considered for specialist referral to a gynaecologist oncologist. PMID:15244121

  12. In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production.

    PubMed

    Ito, Kiyoshi; Miki, Yasuhiro; Suzuki, Takashi; McNamara, Keely May; Sasano, Hironobu

    2016-07-01

    In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated. PMID:27287451

  13. General Information About Endometrial Cancer

    MedlinePlus

    ... Research Endometrial Cancer Treatment (PDQ®)–Patient Version General Information About Endometrial Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  14. Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis

    PubMed Central

    Wei, Linxuan; Liu, Xiaolin; Zhang, Wenjing; Wei, Yuyan; Li, Yingwei; Zhang, Qing; Dong, Ruifen; Kwon, Jungeun Sarah; Liu, Zhaojian; Zheng, Wenxin; Kong, Beihua

    2016-01-01

    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. PMID:27186400

  15. 1. Mill exterior, high grade chute partially restored on the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Mill exterior, high grade chute partially restored on the outside of mill building center of picture. Looking northeast from below bridge. - Kennecott Copper Corporation, Concentration Mill, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  16. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  17. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  18. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  19. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  20. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  1. High-Grading Lunar Samples for Return to Earth

    NASA Technical Reports Server (NTRS)

    Allen, Carlton; Sellar, Glenn; Nunez, Jorge; Winterhalter, Daniel; Farmer, Jack

    2009-01-01

    Astronauts on long-duration lunar missions will need the capability to "high-grade" their samples to select the highest value samples for transport to Earth and to leave others on the Moon. We are supporting studies to defile the "necessary and sufficient" measurements and techniques for highgrading samples at a lunar outpost. A glovebox, dedicated to testing instruments and techniques for high-grading samples, is in operation at the JSC Lunar Experiment Laboratory.

  2. Endometrial regeneration and endometrial stem/progenitor cells.

    PubMed

    Gargett, Caroline E; Nguyen, Hong P T; Ye, Louie

    2012-12-01

    The functional layer of the human endometrium is a highly regenerative tissue undergoing monthly cycles of growth, differentiation and shedding during a woman's reproductive years. Fluctuating levels of circulating estrogen and progesterone orchestrate this dramatic remodeling of human endometrium. The thin inactive endometrium of postmenopausal women which resembles the permanent basal layer of cycling endometrium retains the capacity to respond to exogenous sex steroid hormones to regenerate into a thick functional endometrium capable of supporting pregnancy. Endometrial regeneration also follows parturition and endometrial resection. In non menstruating rodents, endometrial epithelium undergoes rounds of proliferation and apoptosis during estrus cycles. The recent identification of adult stem cells in both human and mouse endometrium suggests that epithelial progenitor cells and the mesenchymal stem/stromal cells have key roles in the cyclical regeneration of endometrial epithelium and stroma. This review will summarize the evidence for endometrial stem/progenitor cells, examine their role in mouse models of endometrial epithelial repair and estrogen-induced endometrial regeneration, and also describe the generation of endometrial-like epithelium from human embryonic stem cells. With markers now available for identifying endometrial mesenchymal stem/stromal cells, their possible role in gynecological diseases associated with abnormal endometrial proliferation and their potential application in cell-based therapies to regenerate reproductive and other tissues will be discussed. PMID:22847235

  3. Cancer Statistics: Endometrial Cancer

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 60,050 % of All New Cancer Cases 3.6% Estimated Deaths in 2016 10,470 % of All Cancer ... of This Cancer : In 2013, there were an estimated 635,437 women living with endometrial cancer in ...

  4. Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions

    PubMed Central

    Zhang, Hui; Wen, Jia; Xu, Pi-Li; Chen, Rui; Yang, Xi; Zhou, Lian-Er; Jiang, Ping; Wan, An-Xia; Liao, Qin-Ping

    2016-01-01

    Background: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. Methods: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. Results: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. Conclusions: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions. PMID:27270542

  5. Cancer of the Uterus (Endometrial Cancer)

    MedlinePlus

    ... Management Education & Events Advocacy For Patients About ACOG Cancer of the Uterus [Endometrial Cancer] Home For Patients Search FAQs Cancer of the ... Uterus [Endometrial Cancer] FAQ097, May 2011 PDF Format Cancer of the Uterus [Endometrial Cancer] Gynecologic Problems What ...

  6. Surgical Outcomes of High-Grade Spinal Cord Gliomas

    PubMed Central

    Hida, Kazutoshi; Yano, Syunsuke; Aoyama, Takeshi; Koyanagi, Izumi; Houkin, Kiyohiro

    2015-01-01

    Study Design A retrospective study. Purpose The purpose of this study was to obtain useful information for establishing the guidelines for treating high-grade spinal cord gliomas. Overview of Literature The optimal management of high-grade spinal cord gliomas remains controversial. We report the outcomes of the surgical management of 14 high-grade spinal glioma. Methods We analyzed the outcomes of 14 patients with high-grade spinal cord gliomas who were surgically treated between 1989 and 2012. Survival was charted with the Kaplan-Meier plots and comparisons were made with the log-rank test. Results None of the patients with high-grade spinal cord gliomas underwent total resection. Subtotal resection was performed in two patients, partial resection was performed in nine patients, and open biopsy was performed in three patients. All patients underwent postoperative radiotherapy and six patients further underwent radiation cordotomy. The median survival time for patients with high-grade spinal cord gliomas was 15 months, with a 5-year survival rate of 22.2%. The median survival time for patients with World Health Organization grade III tumors was 25.5 months, whereas the median survival time for patients with glioblastoma multiforme was 12.5 months. Both univariate and multivariate Cox proportional hazards models demonstrated a significant effect only in the group that did not include cervical cord lesion as a factor associated with survival (p=0.04 and 0.03). Conclusions The surgical outcome of patients diagnosed with high-grade spinal cord gliomas remains poor. Notably, only the model which excluded cervical cord lesions as a factor significantly predicted survival. PMID:26713128

  7. Does Cytological Laboratory Holds the Responsibility for the Low Sensitivity of the PAP Test in Detecting Endometrial Cancer?

    PubMed

    Milicić, Valerija; Matić, Tereza Solocki; Martinek, Vjenceslav; Tomasković, Igor; Ramljak, Vesna

    2015-09-01

    Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer

  8. Clinicopathological characteristics of patients with synchronous primary endometrial and ovarian cancers: A review of 43 cases

    PubMed Central

    LIU, YUANTAO; LI, JUN; JIN, HONGYAN; LU, YING; LU, XIN

    2013-01-01

    Synchronous primary endometrial and ovarian cancers are uncommon. The purpose of this study was to evaluate the clinicopathological characteristics, treatment and prognosis of synchronous primary endometrial and ovarian cancers. The clinicopathological characteristics of 43 patients with synchronous primary endometrial and ovarian cancers in the Obstetrics and Gynecology Hospital of Fudan University between 1999 and 2009 were retrospectively reviewed. Our results revealed that the median age at the time of diagnosis was 51 years (range, 29–71). The common presenting symptoms were abnormal uterine bleeding (AUB, 65.12%), abdominal mass (25.58%), abdominal pain and abdominal fullness (39.53%). An elevated CA125 level was observed in the majority of patients (n=20, 76.9%). Endometrioid type accounted for 60.47% of uterine carcinomas and different pathological types, including serous adenocarcinoma, clear cell carcinoma, adenosquamous and acanthoadenocarcinoma, were also identified in synchronous primary endometrial and ovarian cancers. All patients underwent surgical intervention (hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy or debulking surgery). The 5-year survival rate was 86.05% and nine patients had recurrence (20.93%). The early stage group (FIGO stages I and II) had more favorable prognosis than the advanced stage group (FIGO stages III and IV; P<0.05). In conclusion, synchronous primary endometrial and ovarian cancers are different from either primary endometrial carcinoma or ovarian cancer and are usually identified at early stages with a good prognosis. PMID:23255933

  9. Mutations in chromatin machinery and pediatric high-grade glioma

    PubMed Central

    Lulla, Rishi R.; Saratsis, Amanda Muhs; Hashizume, Rintaro

    2016-01-01

    Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors. PMID:27034984

  10. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  11. Mutations in chromatin machinery and pediatric high-grade glioma.

    PubMed

    Lulla, Rishi R; Saratsis, Amanda Muhs; Hashizume, Rintaro

    2016-03-01

    Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors. PMID:27034984

  12. Medical interventions for high grade vulval intraepithelial neoplasia

    PubMed Central

    Pepas, Litha; Kaushik, Sonali; Bryant, Andrew; Nordin, Andy; Dickinson, Heather O

    2014-01-01

    Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. Objectives To evaluate the effectiveness and safety of medical interventions for high grade VIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported

  13. Uterine sarcoma Part II-Uterine endometrial stromal sarcoma: The TAG systematic review.

    PubMed

    Horng, Huann-Cheng; Wen, Kuo-Chang; Wang, Peng-Hui; Chen, Yi-Jen; Yen, Ming-Shyen; Ng, Heung-Tat

    2016-08-01

    Endometrial stromal tumors are rare uterine tumors (<1%). Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and uterine undifferentiated sarcoma (UUS). This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B) gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS). Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors. PMID:27590366

  14. Expression of MIF and c-erbB-2 in endometrial cancer

    PubMed Central

    XIAO, WEI; DONG, XIUJUAN; ZHAO, HONGHUI; HAN, SHIYU; NIE, RUIXUE; ZHANG, XIAHUA; AN, RUIFANG

    2016-01-01

    The aim of the present study was to investigate the expression of c-erbB-2 and macrophage migration inhibitory factor (MIF) in endometrial cancer and to elucidate the significance of the early diagnosis and prognosis of endometrial cancer. The gene copy number of c-erbB-2 and MIF was characterized by reverse transcription quantitative polymerase chain reaction and the reactivity was assessed by immunohistochemistry in 70 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. A correlation between age, tumor stage, grade, myometrial invasion and lymph node metastasis was observed. The mRNA expression of c-erbB-2 and MIF was high in endometrial carcinoma. The positive expression rate of MIF protein in normal endometrium, atypical hyperplasia and endometrial carcinoma significantly increased along with the degree of aggravation of the disease by 20 (3/15), 45 (9/20) and 70% (35/50), respectively. The positive expression of MIF and c-erbB-2 was highest in endometrial cancer and a significantly higher level of protein was observed in tumors at stage I, stage G1, with a depth of myometrial invasion <0.4 cm and no lymph node metastasis. The protein expression of c-erbB-2 in endometrial cancer was higher in tumors at the G2-3 phase, clinical stage III–IV, lymph node metastasis, and had no association with the depth of myometrial invasion and age. MIF and c-erbB-2 were correlated with the occurrence and the development of endometrial cancer, and thus can be used for the early diagnosis and prognosis of endometrial cancer. The present study laid the foundation for identifying new treatments for endometrial cancer. PMID:26985869

  15. The cancer marker neutrophil gelatinase-associated lipocalin is highly expressed in human endometrial hyperplasia.

    PubMed

    Liao, Chi-Jr; Huang, Yen Hua; Au, Heng-Kien; Wang, Le-Ming; Chu, Sin-Tak

    2012-02-01

    Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, β-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, β-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and β-catenin mRNA expression (r = -0.42 and r = -0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma. PMID:21573795

  16. Serous tubal intraepithelial carcinoma, chronic fallopian tube injury, and serous carcinoma development.

    PubMed

    Malmberg, Karin; Klynning, Charlotta; Flöter-Rådestad, Angelique; Carlson, Joseph W

    2016-06-01

    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. PMID:27003156

  17. A clinically applicable molecular-based classification for endometrial cancers

    PubMed Central

    Talhouk, A; McConechy, M K; Leung, S; Li-Chang, H H; Kwon, J S; Melnyk, N; Yang, W; Senz, J; Boyd, N; Karnezis, A N; Huntsman, D G; Gilks, C B; McAlpine, J N

    2015-01-01

    Background: Classification of endometrial carcinomas (ECs) by morphologic features is inconsistent, and yields limited prognostic and predictive information. A new system for classification based on the molecular categories identified in The Cancer Genome Atlas is proposed. Methods: Genomic data from the Cancer Genome Atlas (TCGA) support classification of endometrial carcinomas into four prognostically significant subgroups; we used the TCGA data set to develop surrogate assays that could replicate the TCGA classification, but without the need for the labor-intensive and cost-prohibitive genomic methodology. Combinations of the most relevant assays were carried forward and tested on a new independent cohort of 152 endometrial carcinoma cases, and molecular vs clinical risk group stratification was compared. Results: Replication of TCGA survival curves was achieved with statistical significance using multiple different molecular classification models (16 total tested). Internal validation supported carrying forward a classifier based on the following components: mismatch repair protein immunohistochemistry, POLE mutational analysis and p53 immunohistochemistry as a surrogate for ‘copy-number' status. The proposed molecular classifier was associated with clinical outcomes, as was stage, grade, lymph-vascular space invasion, nodal involvement and adjuvant treatment. In multivariable analysis both molecular classification and clinical risk groups were associated with outcomes, but differed greatly in composition of cases within each category, with half of POLE and mismatch repair loss subgroups residing within the clinically defined ‘high-risk' group. Combining the molecular classifier with clinicopathologic features or risk groups provided the highest C-index for discrimination of outcome survival curves. Conclusions: Molecular classification of ECs can be achieved using clinically applicable methods on formalin-fixed paraffin-embedded samples, and provides

  18. Krüppel-Like factor 9 loss-of-expression in human endometrial carcinoma links altered expression of growth-regulatory genes with aberrant proliferative response to estrogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endometrial cancer is the most commonly diagnosed female genital tract malignancy. Krüppel-like Factor 9 (KLF9), a member of the evolutionarily conserved Sp-family of transcription factors, is expressed in uterine stroma and glandular epithelium where it affects cellular proliferation, differenti...

  19. A Trial for Patients With Advanced/Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2009-11-13

    Neoplasms; Neoplasms by Site; Urogenital Neoplasms; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Cancer of Endometrium; Endometrial Cancer; Cancer of the Endometrium; Endometrium Cancer; Neoplasms, Endometrial

  20. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    PubMed Central

    Ohman, Anders W.; Hasan, Noor; Dinulescu, Daniela M.

    2014-01-01

    The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early-stages and improving the disease prognosis. PMID:25478323

  1. FOXO3a loss is a frequent early event in high-grade pelvic serous carcinogenesis.

    PubMed

    Levanon, K; Sapoznik, S; Bahar-Shany, K; Brand, H; Shapira-Frommer, R; Korach, J; Hirsch, M S; Roh, M H; Miron, A; Liu, J F; Vena, N; Ligon, A H; Fotheringham, S; Bailey, D; Flavin, R J; Birrer, M J; Drapkin, R I

    2014-08-28

    Serous ovarian carcinoma is the most lethal gynecological malignancy in Western countries. The molecular events that underlie the development of the disease have been elusive for many years. The recent identification of the fallopian tube secretory epithelial cells (FTSECs) as the cell-of-origin for most cases of this disease has led to studies aimed at elucidating new candidate therapeutic pathways through profiling of normal FTSECs and serous carcinomas. Here we describe the results of transcriptional profiles that identify the loss of the tumor suppressive transcription factor FOXO3a in a vast majority of high-grade serous ovarian carcinomas. We show that FOXO3a loss is a hallmark of the earliest stages of serous carcinogenesis and occurs both at the DNA, RNA and protein levels. We describe several mechanisms responsible for FOXO3a inactivity, including chromosomal deletion (chromosome 6q21), upregulation of miRNA-182 and destabilization by activated PI3K and MEK. The identification of pathways involved in the pathogenesis of ovarian cancer can advance the management of this disease from being dependant on surgery and cytotoxic chemotherapy alone to the era of targeted therapy. Our data strongly suggest FOXO3a as a possible target for clinical intervention. PMID:24077281

  2. Inflammation and endometrial bleeding.

    PubMed

    Berbic, M; Ng, C H M; Fraser, I S

    2014-12-01

    Most of the key physiological processes in the human reproductive tract involve a significant inflammatory component. These processes include follicle development, ovulation, implantation, pregnancy, labor, postpartum, remodeling and menstruation. In this context, the term 'inflammation' usually means an influx of leukocytes ('immune cells'), often of different types, into a reproductive tract tissue. These examples of inflammation are not overtly associated with any infective process. There may also be evidence that these invading leukocytes have altered their functions to take on specific and relevant local regulatory roles. Specific sequential changes in different leukocytes can be demonstrated within human endometrium during the different phases of the normal menstrual cycle. Leukocytes are fairly sparse in numbers through the proliferative phase, but increase substantially into and through the secretory phase, so much so that around 40% of all stromal cells in the premenstrual phase are leukocytes, mainly uterine natural killer cells, a large granulated lymphocyte. Other leukocytes which play key roles in menstruation appear to be macrophages, mast cells, dendritic cells, neutrophils, eosinophils and regulatory T cells. Premenstrual withdrawal of progesterone increases the endometrial expression of inflammatory mediators, including IL-8 and MCP-1, which are believed to drive endometrial leukocyte recruitment at this time. Macrophages and neutrophils are rich sources of defensins and whey acid protein motif proteins, which play important roles in ensuring microbial protection while the epithelial barrier is disrupted. Mast cells are increasingly activated as the menstrual phase approaches, and leukocyte proteases trigger a cascade of matrix metalloproteinases and degradation of extracellular matrix. Dendritic cells and other antigen-presenting cells (e.g. macrophages) almost certainly facilitate clearance of cellular debris from the uterine cavity, and reduce

  3. Aberrant expression of hSef and Sprouty4 in endometrial adenocarcinoma

    PubMed Central

    ZHANG, HUI; GUO, QIUFEN; WANG, XIA; WANG, CHONG; ZHAO, XINGBO; LI, MINGJIANG

    2016-01-01

    Fibroblast growth factor (FGF) 2-mediated signaling of the mitogen-activated protein kinase/RAS/extracellular signal-regulated kinase 1/2 pathway is a critical modulator in angiogenesis and is therefore essential for the pathogenesis of endometrial carcinoma. Human similar expression to FGFs (hSef) and Sprouty4 have each been reported to be negative regulators of FGF signaling. The aim of the present study was to investigate the expression of hSef and Sprouty4 in human endometrial adenocarcinoma. Using immunohistochemistry analysis, the expression of hSef and Sprouty4 was detected in human endometrial adenocarcinomas. Increased hSef expression was found to be present in endometrial adenocarcinomas. In addition, decreased hSef expression was identified in the blood vessels of endometrial adenocarcinoma samples. However, the expression of Sprouty4 was downregulated in human endometrial adenocarcinoma. Aberrant expression of hSef and Sprouty4 are involved in the pathogenesis of human endometrial adenocarcinoma. PMID:26870165

  4. Undifferentiated Carcinoma of the Endometrium: An Expanded Immunohistochemical Analysis Including PAX-8 and Basal-Like Carcinoma Surrogate Markers.

    PubMed

    Ramalingam, Preetha; Masand, Ramya P; Euscher, Elizabeth D; Malpica, Anais

    2016-09-01

    Undifferentiated carcinoma of the endometrium (UCAe) is an aggressive, underrecognized high-grade carcinoma that can occur either in pure form or in conjunction with low-grade endometrioid adenocarcinoma (i.e. dedifferentiated carcinoma). The typical solid growth pattern of UCAe can create a diagnostic dilemma as it is frequently misinterpreted as the solid component of an endometrial carcinoma or as a sarcoma. In addition, the high nuclear:cytoplasmic ratio, high mitotic index, and geographic necrosis are reminiscent of basal-like carcinoma of breast (BLCB). This study was undertaken to determine the role of a selected group of immunomarkers in the distinction of UCAe from other endometrial carcinomas, and assess the expression of DNA mismatch repair proteins, and surrogate BLCB immunomarkers in this type of tumor. Cases of UCAe were stained with antibodies against keratin cocktail, CK8/18, PAX-8, and estrogen receptor: 35 cases; progesterone receptor and Her-2/neu: 33 cases; CD44, e-cadherin, p16, and p53: 32 cases; and CK5/6, EGFR, and c-Kit: 18 cases. In addition, mismatch repair protein markers MLH1, MSH2, MSH6, and PMS2 were performed in 34 cases. We found that PAX-8 expression was lost in most cases (83%). In addition, estrogen and progesterone receptors were negative in 83% and 82% of cases, respectively. Seventy-seven percent of cases were positive for keratin cocktail and keratin 8/18, whereas only 11% of cases were positive for keratin 5/6. p16 was diffusely positive in 34% of cases, whereas p53 was expressed in >75% of the tumor cells in 31% of cases. MLH1 and PMS2 were concurrently lost in 50% of cases, whereas MSH2 and MSH6 were lost in 1 case (3%). E-cadherin and CD44 were completely lost in 50% of cases, whereas Her-2/neu was negative in all cases. EGFR was negative in 67% of cases, whereas 22% of cases showed diffuse membranous staining for this marker. UCAe is a high-grade carcinoma of Müllerian origin which tends to be negative for PAX-8. The

  5. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.

    PubMed

    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

    2016-07-28

    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. PMID:27372738

  6. Therapeutic options for management of endometrial hyperplasia

    PubMed Central

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434

  7. Metabolic vulnerabilities in endometrial cancer.

    PubMed

    Byrne, Frances L; Poon, Ivan K H; Modesitt, Susan C; Tomsig, Jose L; Chow, Jenny D Y; Healy, Marin E; Baker, William D; Atkins, Kristen A; Lancaster, Johnathan M; Marchion, Douglas C; Moley, Kelle H; Ravichandran, Kodi S; Slack-Davis, Jill K; Hoehn, Kyle L

    2014-10-15

    Women with metabolic disorders, including obesity and diabetes, have an increased risk of developing endometrial cancer. However, the metabolism of endometrial tumors themselves has been largely understudied. Comparing human endometrial tumors and cells with their nonmalignant counterparts, we found that upregulation of the glucose transporter GLUT6 was more closely associated with the cancer phenotype than other hallmark cancer genes, including hexokinase 2 and pyruvate kinase M2. Importantly, suppression of GLUT6 expression inhibited glycolysis and survival of endometrial cancer cells. Glycolysis and lipogenesis were also highly coupled with the cancer phenotype in patient samples and cells. To test whether targeting endometrial cancer metabolism could be exploited as a therapeutic strategy, we screened a panel of compounds known to target diverse metabolic pathways in endometrial cells. We identified that the glycolytic inhibitor, 3-bromopyruvate, is a powerful antagonist of lipogenesis through pyruvylation of CoA. We also provide evidence that 3-bromopyruvate promotes cell death via a necrotic mechanism that does not involve reactive oxygen species and that 3-bromopyruvate impaired the growth of endometrial cancer xenografts. PMID:25205105

  8. High-Grade Sarcomas Mimicking Traumatic Intramuscular Hematomas

    PubMed Central

    Gomez, Pablo; Morcuende, Jose

    2004-01-01

    We reported on three patients with high-grade soft-tissue sarcomas mimicking traumatic intramuscular hematomas. Patients had an episode of trauma to the extremity, and after initial clinical and imaging evaluations they were considered to have muscular hematomas. The lesions increased in size over time, leading to further evaluations that demonstrated the actual diagnosis. We conducted a retrospective review of the clinical findings, magnetic resonance images, and computed tomography scans to assess characteristics that will help in the differential diagnosis. We conclude that intramuscular hematomas following trauma should be approached with a high degree of clinical suspicion. MRI analysis can be used as an important diagnostic tool, but the results must be seen in the context of the clinical history. MRI is not sensitive or specific enough to rule out malignancy. The diagnosis of a high-grade sarcoma must be considered in these patients and any doubt should be resolved with a biopsy. PMID:15296215

  9. Promising novel therapies for the treatment of endometrial cancer

    PubMed Central

    Gehrig, Paola A.; Bae-Jump, Victoria L.

    2014-01-01

    Objectives To discuss the novel agents which are being developed for the treatment of advanced and recurrent endometrial carcinoma and to review other molecular targets that may be interesting in the treatment of this disease. While the majority of women with endometrial cancer enjoy a relatively good prognosis, the options for those women who suffer from a disease recurrence are limited and there is a need to identify novel agents. Methods A review of clinical trials of novel therapeutic agents and their molecular targets is provided. In addition, a review of the current literature on other potential molecular targets for endometrial cancer was performed. Results Several phase II trials of novel agents, both alone and in combination with traditional cytotoxic chemotherapy, have been completed or are nearing completion. It appears that the targeted agents may have the most efficacy in combination with cytotoxic chemotherapy or in a multi-targeted agent approach. Conclusions Chemotherapy offers the opportunity for a meaningful response rate in women with endometrial cancer, but the responses are often short lived and cure is uncommon in the setting of recurrent disease. The recent increase in molecular targets has led to the availability of many novel therapies. Determining how these agents are to be used, alone or in combination with “standard” therapies, needs to be defined and translational studies are needed to develop rational combinations of these novel agents before we can move into clinical trials. PMID:19903572

  10. Selective nonoperative management of high grade splenic trauma.

    PubMed

    Branco, Bernardino C; Tang, Andrew L; Rhee, Peter; Fraga, Gustavo Pereira; Nascimento, Bartolomeu; Rizoli, Sandro; O'Keeffe, Terence

    2013-01-01

    The "Evidence-based Telemedicine - Trauma & Acute Care Surgery" (EBT-TACS) Journal Club performed a critical review of the literature and selected three up-to-date articles on the management of splenic trauma. Our focus was on high-grade splenic injuries, defined as AAST injury grade III-V. The first paper was an update of the 2003 Eastern Association for the Surgery of Trauma (EAST) practice management guidelines for nonoperative management of injury to the spleen. The second paper was an American Association for the Surgery of Trauma (AAST) 2012 plenary paper evaluating the predictive role of contrast blush on CT scan in AAST grade IV and V splenic injuries. Our last article was from Europe and investigates the effects of angioembolization of splenic artery on splenic function after high-grade splenic trauma (AAST grade III-V). The EBT-TACS Journal Club elaborated conclusions and recommendations for the management of high-grade splenic trauma. PMID:23912375

  11. What Are the Key Statistics about Endometrial Cancer?

    MedlinePlus

    ... cancer? Next Topic Endometrial cancer risk factors Key statistics for endometrial cancer? How common is endometrial cancer? ... endometrial cancer. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  12. The effect of Cordyceps extract and a mixture of Ganoderma lucidum/Agaricus Blazi Murill extract on human endometrial cancer cell lines in vitro.

    PubMed

    Hahne, Jens C; Meyer, Susanne R; Dietl, Johannes; Honig, Arnd

    2014-07-01

    Endometrial carcinoma is the most common gynaecological malignancy. Nevertheless there is a lack of curative therapies, especially for patients diagnosed with late stage, recurrent or aggressive disease, who have a poor prognosis. Cordyceps Sinensis, Ganoderma lucidum and Agaricus Blazi Murill are three fungi widely used in traditional Chinese medicine, and effects as adjuvants in tumour therapy have been demonstrated. However, the function and effects of these fungi in regard to endometrial cancer are not known. Three endometrial cancer cell lines, Ishikawa, Hec-1A and AN3-CA (derived from endometrial cancers grade I, II and III, respectively), were used to determine the effect of the fungi extracts on endometrial cancer cell function and to analyze the molecular mechanism. All fungi extracts had an inhibitory effect on cell viability and proliferation most probably exerted through induction of autophagy. Our data suggest that these fungi extracts may be used as adjuvants in endometrial tumour therapy. PMID:24805296

  13. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK–NF-κB signaling pathway

    SciTech Connect

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun; Gu, Wei; Wan, Xiao-Ping

    2014-03-28

    Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.

  14. Drugs Approved for Endometrial Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  15. Mucoepidermoid carcinoma

    PubMed Central

    Devaraju, Ramaraju; Gantala, Ramlal; Aitha, Harisha; Gotoor, Srikanth Goud

    2014-01-01

    Salivary gland tumours comprise almost 5% of head and neck malignancies. Minor salivary gland tumours account for 10–15% of all salivary gland neoplasms and are usually malignant. The second most common minor salivary gland tumour (12–40% globally) is mucoepidermoid carcinoma. Mucoepidermoid carcinoma is more frequent in females, occurs in the fifth decade of life and is usually found in the parotid gland. However, the palate is a frequent site when it occurs in the minor glands. We report a case of a high-grade variant of mucoepidermoid carcinoma in the right retromolar trigone of a 21-year man which was treated with wide excision of the tumour with a 1.5 cm margin. Reconstruction was done with a buccal fat pad posteriorly with a pedicled lateral tongue flap. Temporal stripping and right coronoidectomy was carried out in case of post-surgical wound contraction. The patient is currently under periodic review. PMID:25085946

  16. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK-NF-κB signaling pathway.

    PubMed

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun; Gu, Wei; Wan, Xiao-Ping

    2014-03-28

    Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK-NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma. PMID:24582558

  17. Irradiation of Pediatric High-Grade Spinal Cord Tumors

    SciTech Connect

    Tendulkar, Rahul D.; Pai Panandiker, Atmaram S.; Wu Shengjie; Kun, Larry E.; Broniscer, Alberto; Sanford, Robert A.; Merchant, Thomas E.

    2010-12-01

    Purpose: To report the outcome using radiation therapy (RT) for pediatric patients with high-grade spinal cord tumors. Methods and Materials: A retrospective chart review was conducted that included 17 children with high-grade spinal cord tumors treated with RT at St. Jude Children's Research Hospital between 1981 and 2007. Three patients had gross total resection, 11 had subtotal resection, and 3 underwent biopsy. The tumor diagnosis was glioblastoma multiforme (n = 7), anaplastic astrocytoma (n = 8), or anaplastic oligodendroglioma (n = 2). Seven patients received craniospinal irradiation (34.2-48.6 Gy). The median dose to the primary site was 52.2 Gy (range, 38-66 Gy). Results: The median progression-free and overall survivals were 10.8 and 13.8 months, respectively. Local tumor progression at 12 months (79% vs. 30%, p = 0.02) and median survival (13.1 vs. 27.2 months, p = 0.09) were worse for patients with glioblastoma multiforme compared with anaplastic astrocytoma or oligodendroglioma. The median overall survival was shorter for patients when failure included neuraxis dissemination (n = 8) compared with local failure alone (n = 5), 9.6 vs. 13.8 months, p = 0.08. Three long-term survivors with World Health Organization Grade III tumors were alive with follow-up, ranging from 88-239 months. Conclusions: High-grade spinal cord primary tumors in children have a poor prognosis. The propensity for neuraxis metastases as a component of progression after RT suggests the need for more aggressive therapy.

  18. Role of hyaluronan and hyaluronan synthase in endometrial cancer.

    PubMed

    Yabushita, Hiromitsu; Kishida, Tameko; Fusano, Kanako; Kanyama, Kouhei; Zhuo, Lisheng; Itano, Naoki; Kimata, Koji; Noguchi, Masayoshi

    2005-06-01

    The aim of this study was to determine if the immunohistochemical expression of hyaluronan synthase (HAS) and serum levels of hyaluronan correlate with the clinicopathological manifestations of endometrial carcinoma. Sera were obtained from 59 endometrial cancer patients and 22 post-menopausal healthy women. Concentration of hyaluronan in sera was measured by an inhibitory ELISA using a hyaluronan-binding protein. Tissues obtained from 59 endometrial cancer patients were immunostained by the avidin-biotin-peroxidase complex method using anti-HAS1, anti-HAS2, anti-HAS3 and anti-CD44 antibody. A section was defined as having positive expression when >50% of the tumor cells were intensely stained. The expression of HAS1 was related to the depth of myometrial invasion, histological grade and lymph-vascular space involvement, but the expression of HAS2 and HAS3 was unrelated to these parameters. CD44 expression occurred more frequently in the HAS2- or HAS3-positive groups than in the HAS2- or HAS3-negative groups, and the expression of HAS1 was unrelated to CD44 expression. Serum levels of hyaluronan were higher in the endometrial cancer group than in the healthy control group, and increased with depth of myometrial invasion, histological grade and lymph-vascular space involvement. Serum hyaluronan levels were higher in the HAS1-positive group than in the HAS1-negative group, but the expression of HAS2 and HAS3 was unrelated to serum hyaluronan levels. HAS1 expression and an increase in serum hyaluronan in endometrial cancer may be associated with disease progression through myometrial invasion and lymph-vascular space involvement. PMID:15870928

  19. Can Endometrial Cancer Be Found Early?

    MedlinePlus

    ... Next Topic Signs and symptoms of endometrial cancer Can endometrial cancer be found early? In most cases, ... reach an advanced stage before signs and symptoms can be noticed. More information can be found in “ ...

  20. Photodynamic therapy toward selective endometrial ablation

    NASA Astrophysics Data System (ADS)

    Tadir, Yona; Tromberg, Bruce J.; Krasieva, Tatiana B.; Berns, Michael W.

    1993-05-01

    Potential applications of photodynamic therapy for endometrial disease are discussed. Experimental models that may lead to diagnosis and treatment of endometriosis as well as selective endometrial ablation are summarized.

  1. Biomechanics of high-grade spondylolisthesis with and without reduction.

    PubMed

    Wang, Wenhai; Aubin, Carl-Eric; Cahill, Patrick; Baran, George; Arnoux, Pierre-Jean; Parent, Stefan; Labelle, Hubert

    2016-04-01

    The clinical advantages of reducing spondylolisthesis over fusion in situ have several intuitive reasons such as restore the spinal column into a more anatomic relationship and alignment. However, there is only little evidence in the literature supporting the theoretical advantages of reduction, and its effect on spinopelvic alignment remains poorly defined. In this study, a comprehensive finite element model was developed to analyze the biomechanics of the spine after spinal fusion at L5-S1 in both types of high-grade spondylolisthesis (balanced and unbalanced pelvis). The relevant clinical indices (i.e. spondylolisthesis grade and Dubousset lumbosacral angle), the displacement of L4-L5, pressure within the annulus and nucleus, and stress at L4-L5 were evaluated and compared. The model can well predict the changes of the important clinical indices during the surgery. For a balanced pelvis, the reduction has a minimal effect on the biomechanical conditions at the adjacent level during postsurgical activities. In the unbalanced case, reduction induced larger deformation in the lumbosacral region and a higher stress concentration at adjacent level. Whether such a stress concentration can lead to long-term disc degeneration is not known. The results provide additional information for the clinician considering reduction of high-grade spondylolisthesis. PMID:26233229

  2. Role of MicroRNAs in carcinogenesis that potential for biomarker of endometrial cancer.

    PubMed

    Widodo; Djati, Muhammad Sasmito; Rifa'i, Muhaimin

    2016-05-01

    The non-invasive diagnostic tool for early detection of endometrial cancer still limited. The etiology of this disease is believed to be associated with disharmony hormone production. One predominant factor that regulate hormone production is microRNA (miRNAs). Some studies reported that miRNAs play a significant role in the process carcinogenesis. We have identified 12 of miRNAs that potentially have a role in controlling endometrial carcinogenesis pathways. Further analysis suggested that these miRNA targeted genes that regulate the early development of endometrial cancer. These genes cluster into several functional groups involving a process of angiogenesis, apoptosis, cell cycle, cell proliferation and p53 pathways. Some of the genes are PTEN, GSK3b, and TP53, which are a tumor suppressor that control the process of growth arrest, DNA Repair, and Apoptosis. Upregulation of the miRNA may obstruct the cell ability to control the cell cycle. This study was found three miRNA that plays a role in the development of endometrial cancer. The hsa-miR-495 and hsa-miR-152 were repressed in endometrial cancer compared to normal tissue. The microRNA regulate genes that control proliferation and cell survival. Moreover, hsa-miR-181d was upregulated to control expression a tumor suppressor gene, PTEN to protect the cancer cell from apoptosis. Further investigation to validate the function of the miRNA is a warrant for developing biomarkers of endometrial carcinoma. PMID:27006767

  3. The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

    PubMed Central

    Kamieniak, Marta M.; Muñoz-Repeto, Ivan; Borrego, Salud; Hernando, Susana; Hernández-Agudo, Elena; Heredia Soto, Victoria; Márquez-Rodas, Ivan; Echarri, María José; Lacambra-Calvet, Carmen; Sáez, Raquel; Redondo, Andrés; Benítez, Javier

    2016-01-01

    Objective We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Methods In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Results Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. Conclusion Low

  4. Primary High-Grade Poorly Differentiated Angiosarcoma of an Intra-parotid Lymph Node.

    PubMed

    Ducharne-Asuaje, Eugenia; Dorion, Dominique; Lamarre, Louis; Coindre, Jean Michel; Geha, Sameh

    2016-06-01

    Head and neck angiosarcoma is an infrequent malignant vascular tumor most commonly found in the skin and soft tissue of the head and neck. Most head and neck angiosarcomas are metastatic to cervical lymph nodes from other primitive location. We describe herein a case of primary high-grade poorly differentiated angiosarcoma arising in an intra-parotid lymph node, discuss the value of immunohistochemical stains for differential diagnosis, and review the literature concerning head and neck angiosarcoma. A 47-year-old man presented with a painless mass that had grown for a period of 6 months in the parotid area. The CT-scan revealed a left parotid lesion of 17 mm. Fine needle aspiration was considered suspicious for lymphoma or poorly differentiated carcinoma. A superficial parotidectomy was performed. On gross examination, the lesion was a well-defined, gray, homogeneous mass of 15 mm of diameter. Microscopic examination showed a normal parotid tissue and a poorly differentiated malignant neoplasm in an intra-parotid lymph node. The tumor had a pseudo-alveolar pattern, with large pleomorphic epithelioid cells, abundant eosinophilic cytoplasm, large vesicular nuclei, and one or more prominent nucleoli. Atypical mitoses were seen. Neoplastic malignant cells stained positive for Vimentin, CD31, D2-40, factor VIII, ERG, and partially for CD34. A positron emission tomography scan was made to search for a primary neoplasia, but no other tumor was localized. The diagnosis of primary high-grade, poorly differentiated, intra-parotid lymph node angiosarcoma was established. PMID:25930154

  5. PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

    PubMed Central

    Hernández, Norma A; Correa, Elma; Avila, Esther P; Vela, Teresa A; Pérez, Víctor M

    2009-01-01

    Background The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality. Methods In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor. Results Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009). Conclusion Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients. PMID:19538737

  6. DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions.

    PubMed

    Sun, Yin; Li, Shu; Shen, Keng; Ye, Shuang; Cao, Dongyan; Yang, Jiaxin

    2015-01-01

    Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients' samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54), cervical intraepithelial neoplasia grade 2 (CIN2, n=47), cervical intraepithelial neoplasia grade 3 (CIN3, n=56) and cervical squamous cell carcinomas (SCS, n=45). We found there were a significant positive correlation between the promoter methylation status of DAPK1 and cervical disease grade (P=0.022). In addition, the methylated promoters of DAPK1 combined with MGMT, MGMT combined with RARB, DAPK1 combined with RARB were positive correlated with cervical disease grade (P < 0.05). All three genes promoters methylated were positive correlated with cervical disease grade (P < 0.001). Receiver operating characteristic (ROC) curves was conducted to evaluate whether the three genes methylation could be used to be a potential marker for diagnosing high grade cervical disease (HSIL and SCC). The cutoff values for the methylation rates of all these genes were 0-5%. Regrettably, only the methylation of MGMT combined with DAPK1 gave 43.4% sensitivity and 68.6% specificity. The current results indicated that MS-HRM-based testing for DNA methylations of MGMT plus DAPK1 genes holds some promise for high grade cervical disease screening. PMID:26823825

  7. DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions

    PubMed Central

    Sun, Yin; Li, Shu; Shen, Keng; Ye, Shuang; Cao, Dongyan; Yang, Jiaxin

    2015-01-01

    Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients’ samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54), cervical intraepithelial neoplasia grade 2 (CIN2, n=47), cervical intraepithelial neoplasia grade 3 (CIN3, n=56) and cervical squamous cell carcinomas (SCS, n=45). We found there were a significant positive correlation between the promoter methylation status of DAPK1 and cervical disease grade (P=0.022). In addition, the methylated promoters of DAPK1 combined with MGMT, MGMT combined with RARB, DAPK1 combined with RARB were positive correlated with cervical disease grade (P < 0.05). All three genes promoters methylated were positive correlated with cervical disease grade (P < 0.001). Receiver operating characteristic (ROC) curves was conducted to evaluate whether the three genes methylation could be used to be a potential marker for diagnosing high grade cervical disease (HSIL and SCC). The cutoff values for the methylation rates of all these genes were 0-5%. Regrettably, only the methylation of MGMT combined with DAPK1 gave 43.4% sensitivity and 68.6% specificity. The current results indicated that MS-HRM-based testing for DNA methylations of MGMT plus DAPK1 genes holds some promise for high grade cervical disease screening. PMID:26823825

  8. Project for the National Program of Early Diagnosis of Endometrial Cancer Part II

    PubMed Central

    Bohîlțea, RE; Ancăr, V; Rădoi, V; Furtunescu, F; Bohîlțea, LC

    2015-01-01

    Rationale: Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania. Since 2013, an increased trend of endometrial cancer occurrence has been registered in urban areas as compared with rural ones. Unfortunately, most of the cancer cases are diagnosed too late, in an advanced stage of the disease, resulting into diminished lifetime expectancy. The first part of the article concentrated on issues such as: the description of the study, results, and discussions regarding the study, definitions and terms, risk factors specific for endometrial carcinomas, presentation of the activities of the Program, etc. Objective: Drafting a national program that will serve as an early diagnosis method of endometrial cancer. This second part of the study continues with the presentation of the activities of the Program, analyzes the human resources and materials needed to implement the Program, presents the strategies and the indicators specific for the implementation of the project. Methods and Results: A standardization of the diagnostic steps was proposed and the focus was on 4 key elements for the early diagnosis of endometrial cancer: The first steps were approached in the first part of the study and the second part of the study investigated the proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Discussion: Improving medical practice based on diagnostic algorithms and programs improves and increases the lifetime expectancy, due to the fact that endometrial cancer is early diagnosed and treated before it causes serious health problems or even death. Abbreviations: ASCCP = American Society for Colposcopy and Cervical Pathology, CT = Computerized Tomography, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test

  9. Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers.

    PubMed

    Armes, Jane E; Hammet, Fleur; de Silva, Melanie; Ciciulla, John; Ramus, Susan J; Soo, Wee-Kheng; Mahoney, Alexis; Yarovaya, Natalia; Henderson, Michael A; Gish, Kurt; Hutchins, Anne-Marie; Price, Gareth R; Venter, Deon J

    2004-07-22

    Loss of genetic material from chromosome arm 8p occurs commonly in breast carcinomas, suggesting that this region is the site of one or more tumor-suppressor genes (TSGs). Comparative genomic hybridization analysis showed that 8p loss is more common in breast cancers from pre-menopausal compared with post-menopausal patients, as well as in high-grade breast cancers, regardless of the menopausal status. Subsequent high-resolution gene expression profiling of genes mapped to chromosome arm 8p, on an extended cohort of clinical tumor samples, indicated a similar dichotomy of breast cancer clinicopathologic types. Some of these genes showed differential downregulation in early-onset and later-onset, high-grade cancers compared with lower-grade, later-onset cancers. Three such genes were analysed further by in situ technologies, performed on tissue microarrays representing breast tumor and normal tissue samples. PCM1, which encodes a centrosomal protein, and DUSP4/MKP-2, which encodes a MAP kinase phosphatase, both showed frequent gene and protein loss in carcinomas. In contrast, there was an excess of cases showing loss of expression in the absence of reduced gene copy number of SFRP1, which encodes a dominant-negative receptor for Wnt-family ligands. These candidate TSGs may constitute some of the molecular drivers of chromosome arm 8p loss in breast carcinogenesis. PMID:15184884

  10. TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.

    PubMed

    Schultheis, Anne M; Martelotto, Luciano G; De Filippo, Maria R; Piscuglio, Salvatore; Ng, Charlotte K Y; Hussein, Yaser R; Reis-Filho, Jorge S; Soslow, Robert A; Weigelt, Britta

    2016-07-01

    Endometrial carcinomas (ECs) are heterogeneous at the genetic level. Although TP53 mutations are highly recurrent in serous endometrial carcinomas (SECs), these are also present in a subset of endometrioid endometrial carcinomas (EECs). Here, we sought to define the frequency, pattern, distribution, and type of TP53 somatic mutations in ECs by performing a reanalysis of the publicly available data from The Cancer Genome Atlas (TCGA). A total of 228 EECs (n=186) and SECs (n=42) from the TCGA data set, for which an integrated genomic characterization was performed, were interrogated for the presence and type of TP53 mutations, and for mutations in genes frequently mutated in ECs. TP53 mutations were found in 15% of EECs and 88% of SECs, and in 91% of copy-number-high and 35% of polymerase (DNA directed), epsilon, catalytic subunit (POLE) integrative genomic subtypes. In addition to differences in prevalence, variations in the type and pattern of TP53 mutations were observed between histologic types and between integrative genomic subtypes. TP53 hotspot mutations were significantly more frequently found in SECs (46%) than in EECs (15%). TP53-mutant EECs significantly more frequently harbored a co-occurring PTEN mutation than TP53-mutant SECs. Finally, a subset of TP53-mutant ECs (22%) was found to harbor frameshift or nonsense mutations. Given that nonsense and frameshift TP53 mutations result in distinct p53 immunohistochemical results that require careful interpretation, and that EECs and SECs display different patterns, types, and distributions of TP53 mutations, the use of the TP53/p53 status alone for the differential diagnosis of EECs and SECs may not be sufficient. PMID:26556035

  11. High grade abrasive product development from virtified industrial waste

    SciTech Connect

    Blume, R.D.; Drummond, C.H. III; Sarko, A.

    1996-12-31

    Recent developments in environmental legislation, as well as economic incentives such as the increasing cost of landfilling, have led to a paradigm shift away from encapsulation of hazardous waste. The current focus is recycling and product development utilizing industrial waste as raw materials. Current research has targeted the development of high grade abrasive (Vickers hardness (VHN) > 1000 kgF/mm{sup 2}) for blasting and buffing and polishing applications. In addition to product specific physical properties, the developed formulations must also have processing characteristics necessary for vitrification using a high temperature product burner developed by Seiler Pollution Control Systems, as well as the necessary resistance to leaching of EPA regulated hazardous components. Current work has led to the development of formulations with high VHN (950 kgF/mm{sup 2}), acceptable chemical durability, and high mechanical durability utilizing electric arc furnace dust (KO61) and foundry sand as the major components.

  12. Treatment of children with high grade glioma with nimotuzumab

    PubMed Central

    Cabanas, Ricardo; Saurez, Giselle; Rios, Martha; Alert, Jose; Reyes, Adnolys; Valdes, Jose; Gonzalez, Maria C.; Pedrayes, Jorge L.; Avila, Melba; Herrera, Raiza; Infante, Mariela; Echevarria, Ernesto; Moreno, Myrna; Luaces, Patricia Lorenzo; Ramos, Tania Crombet

    2013-01-01

    Brain tumors are a major cause of cancer-related mortality in children. Overexpression of epidermal growth factor receptor (EGFR) is detected in pediatric brain tumors and receptor density appears to increase with tumor grading. Nimotuzumab is an IgG1 antibody that targets EGFR. Twenty-three children with high-grade glioma (HGG) were enrolled in an expanded access program in which nimotuzumab was administered alone or with radio-chemotherapy. The mean number of doses was 39. Nimotuzumab was well-tolerated and treatment with the antibody yielded a survival benefit: median survival time was 32.66 mo and the 2-y survival rate was 54.2%. This study demonstrated the feasibility of prolonged administration of nimotuzumab and showed preliminary evidence of clinical benefit in HGG patients with poor prognosis. PMID:23575267

  13. Molecular characteristics of pediatric high-grade gliomas

    PubMed Central

    Chamdine, Omar; Gajjar, Amar

    2014-01-01

    SUMMARY High-grade gliomas (HGGs) are extremely lethal tumors. Survival has not changed significantly in the past decades. The only known prognostic factors in pediatric HGGs (pHGGs) are extent of resection and histologic grade. Treatment has historically been based on adult trials because of the rarity of pHGGs and the lack of genomic tools to explore their unique molecular characteristics. The recent advances in molecular biological data helped divide these tumors into distinct subgroups. In this review, the authors focus on major molecular targets of alterations in pHGGs: histone H3.3, telomeres, PDGFRA, IDH, BRAFV600E, ACVR1 and NTRK and briefly highlight the difference with the adult counterpart. PMID:25438814

  14. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

    Endometrial cancer is a common gynecologic malignancy typically diagnosed at early stage and cured with surgery alone. Adjuvant therapy is tailored according to the risk of recurrence, estimated based on the International Federation of Gynecology and Obstetrics (FIGO) stage and other histological factors. The objective of this manuscript is to review the evidence guiding adjuvant therapy for early stage and locally advanced uterine cancer. For patients with early stage disease, minimizing toxicity, while preserving outstanding cure rates remains the major goal. For patients with locally advanced endometrial cancer optimal combined regimens are being defined. Risk stratification based on molecular traits is under development and may aid refine the current risk prediction model and permit personalized approaches for women with endometrial cancer. PMID:24761218

  15. Neoadjuvant chemotherapy for high-grade advanced gastric cancer.

    PubMed

    Yonemura, Y; Sawa, T; Kinoshita, K; Matsuki, N; Fushida, S; Tanaka, S; Ohoyama, S; Takashima, T; Kimura, H; Kamata, T

    1993-01-01

    Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m2, mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1:4) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered. PMID:8511923

  16. Equine Endometrial Gland Density and Endometrial Thickness Vary among Sampling Sites in Thoroughbred Mares

    PubMed Central

    HANADA, Michiko; MAEDA, Yousuke; OIKAWA, Masa-aki

    2012-01-01

    The secretions of the equine endometrial glands are essential for the survival, growth, and development of the conceptus in early pregnancy, and endometrial gland density is directly related to successful pregnancy outcome. Endometrial biopsy is routinely used to assess the reproductive potential of broodmares. Some previous studies have shown that equine endometrial glands are uniformly distributed throughout the uterus; however, other work has shown variation of the endometrial architecture between biopsy sites, suggesting that a single biopsy is not representative of the entire endometrium. The aims of this study were to assess and compare the endometrial gland density and thickness at four sampling sites in the uterus (the central segment of each uterine horn, the uterine horn-body junction, and the caudal portion of the uterine body). Endometrial samples from five nulliparous Thoroughbred mares in diestrus were obtained at necropsy and used for subsequent histomorphometric analysis. The caudal uterine body had a significantly lower endometrial gland density and endometrial thickness than the other sites. This may result in nutrient deprivation and reduced survival of embryos or fetuses in this region of the uterus. The endometrial gland density and endometrial thickness did not significantly differ between the other regions sampled, indicating that they are similarly suitable for embryonic implantation and fetal development. Our results suggest that the endometrial structure of the caudal uterine body of the mare is not representative of the endometrial morphology at other sites. Thus, the caudal uterine body is not a suitable site for routine endometrial biopsy. PMID:24833993

  17. Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth

    PubMed Central

    Holst, Frederik; Hoivik, Erling A.; Gibson, William J.; Taylor-Weiner, Amaro; Schumacher, Steven E.; Asmann, Yan W.; Grossmann, Patrick; Trovik, Jone; Necela, Brian M.; Thompson, E. Aubrey; Meyerson, Matthew; Beroukhim, Rameen; Salvesen, Helga B.; Cherniack, Andrew D.

    2016-01-01

    The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications. PMID:27160768

  18. Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth.

    PubMed

    Holst, Frederik; Hoivik, Erling A; Gibson, William J; Taylor-Weiner, Amaro; Schumacher, Steven E; Asmann, Yan W; Grossmann, Patrick; Trovik, Jone; Necela, Brian M; Thompson, E Aubrey; Meyerson, Matthew; Beroukhim, Rameen; Salvesen, Helga B; Cherniack, Andrew D

    2016-01-01

    The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications. PMID:27160768

  19. Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival

    PubMed Central

    Kamal, A M; Bulmer, J N; DeCruze, S B; Stringfellow, H F; Martin-Hirsch, P; Hapangama, D K

    2016-01-01

    Background: Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described. Methods: The expression pattern and prognostic value of AR in relation to oestrogen (ERα and ERβ) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n=85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR. Results: Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P<0.001) and ERα (P=0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P<0.0001), PR (P<0.0001) and ERβ (P<0.035) compared with LGEC, whilst maintaining weak to moderate ERα. Unlike PR, AR expression in metastatic lesions was significantly (P=0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P<0.0001, P<0.0001, respectively). Conclusions: Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ERα and ERβ may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC. PMID:26930451

  20. Uterine papillary serous carcinoma.

    PubMed

    Moore, Kathleen N; Fader, Amanda Nickles

    2011-06-01

    Uterine papillary serous carcinoma (UPSC) is a histologic variant of endometrial cancer that accounts for only 10% of new cases of uterine cancer but is responsible for 40% of deaths from the disease. UPSC is an aggressive tumor with a predilection for early spread beyond the uterus. Treatment for UPSC typically entails surgery and in most women is followed by multimodality adjuvant therapy. In this review, we describe the epidemiology, natural history, treatment, and outcome of UPSC. PMID:21508697

  1. Surgical interventions for high grade vulval intraepithelial neoplasia

    PubMed Central

    Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial

  2. Inverted (hobnail) high-grade prostatic intraepithelial neoplasia and invasive inverted pattern

    PubMed Central

    ÖZNUR, MELTEM; KOCA, SEVIM BAYKAL; YILDIZ, PELIN; BAHADIR, BURAK; BEHZATOĞLU, KEMAL

    2015-01-01

    High-grade prostatic intraepithelial neoplasia (HGPIN) is considered to be an important precursor for prostatic adenocarcinoma. The present study aimed to investigate the histological features of the uncommon inverted (hobnail) pattern of HGPIN in transrectal ultrasonographic (TRUS) prostatic needle biopsies from 13 cases. These 13 diagnosed cases of inverted HGPIN were identified out of a total of 2,034 TRUS biopsies (0.63%), obtained from patients suspected to have prostate cancer. The hobnail pattern is comprised of secretory cell nuclei, which are histologically localized at the luminal surface of the prostate gland, rather than the periphery, and exhibit reverse polarity. Histological examinations were performed and the results demonstrated that 5 of the 13 cases exhibited pure inverted histology, while HGPIN was observed to be histologically associated with other patterns in the remaining 8 patients. In addition, an association with adenocarcinoma was identified in 7 of the 13 cases. All 7 carcinomas accompanied by inverted HGPIN were conventional acinar adenocarcinoma cases; of note, for these 7 cases, the Gleason score was 7 for each. One acinar adenocarcinoma case accompanying inverted HGPIN demonstrated hobnail characteristics in large areas of the invasive component. It was observed that nuclei were proliferated in the invasive cribriform glands, which was comparable to that of inverted HGPIN, and were located on the cytoplasmic luminal surface; a similar morphology was also observed in individual glands. In conclusion, the results of the present study suggested that the hobnail HGPIN pattern may be of diagnostic importance due to its high association with adenocarcinoma and the high Gleason scores in the accompanying carcinomas. PMID:26622858

  3. Molecular Mechanism Linking BRCA1 Dysfunction to High Grade Serous Epithelial Ovarian Cancers with Peritoneal Permeability and Ascites

    PubMed Central

    Desai, A; Xu, J; Aysola, K; Akinbobuyi, O; White, M; Reddy, VE; Okoli, J; Clark, C; Partridge, EE; Childs, Ed; Beech, DJ; Rice, MV; Reddy, ESP; Rao, VN

    2015-01-01

    Ovarian cancer constitutes the second most common gynecological cancer with a five-year survival rate of 40%. Among the various histotypes associated with hereditary ovarian cancer, high-grade serous epithelial ovarian carcinoma (HGSEOC) is the most predominant and women with inherited mutations in BRCA1 have a lifetime risk of 40–60%. HGSEOC is a challenge for clinical oncologists, due to late presentation of patient, diagnosis and high rate of relapse. Ovarian tumors have a wide range of clinical presentations including development of ascites as a result of deregulated endothelial function thereby causing increased vascular permeability of peritoneal vessels. The molecular mechanisms remain elusive. Studies have shown that fallopian tube cancers develop in women with BRCA1 gene mutations more often than previously suspected. Recent studies suggest that many primary peritoneal cancers and some high-grade serous epithelial ovarian carcinomas actually start in the fallopian tubes. In this article we have addressed the molecular pathway of a recently identified potential biomarker Ubc9 whose deregulated expression due to BRCA1 dysfunction can result in HGSEOC with peritoneal permeability and formation of ascites. We also discuss the role of downstream targets Caveolin-1 and Vascular Endothelial Growth Factor (VEGF) in the pathogenesis of ascites in ovarian carcinomas. Finally we hypothesize a signaling axis between Ubc9 over expression, loss of Caveolin-1 and induction of VEGF in BRCA1 mutant HGSEOC cells. We suggest that Ubc9-mediated stimulation of VEGF as a novel mechanism underlying ovarian cancer aggressiveness and ascites formation. Agents that target Ubc9 and VEGF signaling may represent a novel therapeutic strategy to impede peritoneal growth and spread of HGSEOC. PMID:26665166

  4. Efficient molecular subtype classification of high-grade serous ovarian cancer.

    PubMed

    Leong, Huei San; Galletta, Laura; Etemadmoghadam, Dariush; George, Joshy; Köbel, Martin; Ramus, Susan J; Bowtell, David

    2015-07-01

    High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. PMID:25810134

  5. High SEPT9_i1 Protein Expression Is Associated with High-Grade Prostate Cancers

    PubMed Central

    Gilad, Roni; Meir, Karen; Stein, Ilan; German, Larissa; Pikarsky, Eli; Mabjeesh, Nicola J.

    2015-01-01

    Septins are a family of GTP-binding cytoskeleton proteins expressed in many solid tumors. Septin 9 (SEPT9) in particular was found overexpressed in diverse carcinomas. Herein, we studied the expression of SEPT9 isoform 1 protein (SEPT9_i1) in human prostate cancer specimens. We utilized immunohistochemical staining to study the expression of SEPT9_i1 protein. Staining level was analyzed in association with clinical characteristics and the pathological Gleason grade and score. Fifty human prostate cancer specimens (42 primary tumors and 8 metastatic lesions) were stained by SEPT9_i1 antibody and analyzed. SEPT9_i1 protein was expressed in prostate cancer cells but absent in normal epithelial cells. The intensity of staining was correlated proportionally to pretreatment prostate-specific antigen (PSA) blood levels and Gleason score (P < 0.05). SEPT9_i1 was highly expressed in all metastatic lesions. A significant assocation between SEPT9_i1 expression and high Gleason score on multivariate linear regression analysis was found. We conclude that SEPT9_i1 is expressed in high-grade prostate tumors suggesting it has a significant role in prostate tumorigenesis and that it could serve as a molecular marker for prostate tumor progression. PMID:25898316

  6. Overexpression of Eg5 correlates with high grade astrocytic neoplasm.

    PubMed

    Liu, Liqiong; Liu, Xichun; Mare, Marcus; Dumont, Aaron S; Zhang, Haitao; Yan, Dong; Xiong, Zhenggang

    2016-01-01

    To investigate the relationship between Eg5 and histopathological grade of astrocytoma, Eg5 expression was evaluated by immunohistochemical examination on 88 specimens including 25 cases of glioblastoma (WHO grade IV), 22 cases of anaplastic astrocytoma (WHO grade III), 20 cases of diffuse astrocytoma (WHO grade II), and 21 cases of pilocytic astrocytoma (WHO grade I). The histopathological characteristics and Eg5 expression level of each tumor were assessed and statistically analyzed. Astrocytic tumors exhibited significant correlation of expression of Eg5 with higher WHO histopathological grades (p < 0.001). Eg5 is expressed in 51-98% (mean 76.88%) of neoplastic cells in glioblastoma, 34-57% (mean 43.59%) of neoplastic cells in anaplastic astrocytoma, 6-36% (mean 18.60%) of neoplastic cells in diffuse astrocytoma, and 2-28% (mean 13.48%) of neoplastic cells in pilocytic astrocytoma. In conclusion, overexpression of Eg5 associates with high-grade astrocytic neoplasm, and it may represent an independent diagnostic and prognostic factor in grading astrocytic tumors and predicting prognosis of astrocytic tumor patients. PMID:26456023

  7. Concurrent thermochemoradiotherapy for brain high-grade glioma

    NASA Astrophysics Data System (ADS)

    Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

    2016-08-01

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  8. Positron emission tomography of high-grade gliomas.

    PubMed

    Frosina, Guido

    2016-05-01

    High-grade gliomas [HGG (WHO grades III-IV)] are almost invariably fatal. Imaging of HGG is important for orientating diagnosis, prognosis and treatment planning and is crucial for development of novel, more effective therapies. Given the potentially unlimited number of usable tracing molecules and the elevated number of available radionuclides, PET allows gathering multiple informations on HGG including data on tissue metabolism and drug pharmacokinetics. PET studies on the diagnosis, prognosis and treatment of HGG carried out by most frequently used tracers and radionuclides ((11)C and (18)F) and published in 2014 have been reviewed. These studies demonstrate that a thorough choice of tracers may confer elevated diagnostic and prognostic power to PET imaging of HGG. They also suggest that a combination of PET and MRI may give the most complete and reliable imaging information on HGG and that research on hybrid PET/MRI may be paying back in terms of improved diagnosis, prognosis and treatment planning of these deadly tumours. PMID:26897013

  9. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian Past Issues / Spring 2007 ... of this page please turn Javascript on. Gynecologic Cancers Cervical, Endometrial, and Ovarian NCI estimates that endometrial, ...

  10. What's New in Endometrial Cancer Research and Treatment?

    MedlinePlus

    ... Next Topic Additional resources for endometrial cancer What`s new in endometrial cancer research and treatment? Molecular pathology ... that caused the endometrial cells to become cancerous. New treatments New drugs, combinations of drugs and targeted ...

  11. Combination chemotherapy with docetaxel and carboplatin for elderly patients with endometrial cancer

    PubMed Central

    YOSHIDA, HIROYUKI; IMAI, YUICHI; FUJIWARA, KEIICHI

    2016-01-01

    Approximately half of all endometrial cancer cases are diagnosed in patients aged >65 years. The objective of this study was to compare the tolerability and effectiveness of combination chemotherapy with docetaxel and carboplatin between endometrial cancer patients older and younger than 65 years of age. Chemotherapy-naive patients with endometrial cancer were enrolled in this retrospective study between April, 2008 and March, 2015. The patients received docetaxel (60 mg/m2) and carboplatin (area under the curve of 6 mg/ml/min) on day 1 of a 3-week cycle. The tolerability and effectiveness of this regimen were analyzed. A total of 41 patients with endometrial cancer were enrolled in this study, of whom 26 (63%) were aged <65 years and 15 (37%) were aged ≥65 years. There were no significant differences with regard to Eastern Cooperative Oncology Group performance status score and disease stage between the two groups. Patients aged >65 years were significantly more likely to have serous or clear-cell histology and high-grade tumors compared with the younger group (P=0.014 and 0.012, respectively). Although the number of chemotherapy cycles, cycle delays and treatment interruptions were comparable between older and younger patients, there was a trend toward more dose reductions in the older group (P=0.12). The incidence of hematological toxicities did not differ significantly between the two groups. The incidence of grade 3/4 diarrhea was significantly higher in the older group (P=0.014) and hypersensitivity was significantly more frequent in the younger group (P=0.035). Patients aged ≥65 years had equivalent response rates, progression-free survival and overall survival compared with those aged <65 years. These results suggest that combination chemotherapy with docetaxel and carboplatin was tolerable and effective for the treatment of elderly chemotherapy-naive patients with endometrial cancer. PMID:27123279

  12. Loss of CD73-mediated actin polymerization promotes endometrial tumor progression

    PubMed Central

    Bowser, Jessica L.; Blackburn, Michael R.; Shipley, Gregory L.; Molina, Jose G.; Dunner, Kenneth; Broaddus, Russell R.

    2015-01-01

    Ecto-5′-nucleotidase (CD73) is central to the generation of extracellular adenosine. Previous studies have highlighted a detrimental role for extracellular adenosine in cancer, as it dampens T cell–mediated immune responses. Here, we determined that, in contrast to other cancers, CD73 is markedly downregulated in poorly differentiated and advanced-stage endometrial carcinoma compared with levels in normal endometrium and low-grade tumors. In murine models, CD73 deficiency led to a loss of endometrial epithelial barrier function, and pharmacological CD73 inhibition increased in vitro migration and invasion of endometrial carcinoma cells. Given that CD73-generated adenosine is central to regulating tissue protection and physiology in normal tissues, we hypothesized that CD73-generated adenosine in endometrial carcinoma induces an innate reflex to protect epithelial integrity. CD73 associated with cell-cell contacts, filopodia, and membrane zippers, indicative of involvement in cell-cell adhesion and actin polymerization–dependent processes. We determined that CD73-generated adenosine induces cortical actin polymerization via adenosine A1 receptor (A1R) induction of a Rho GTPase CDC42–dependent conformational change of the actin-related proteins 2 and 3 (ARP2/3) actin polymerization complex member N-WASP. Cortical F-actin elevation increased membrane E-cadherin, β-catenin, and Na+K+ ATPase. Together, these findings reveal that CD73-generated adenosine promotes epithelial integrity and suggest why loss of CD73 in endometrial cancer allows for tumor progression. Moreover, our data indicate that the role of CD73 in cancer is more complex than previously described. PMID:26642367

  13. Gene Tests May Improve Therapy for Endometrial Cancer

    MedlinePlus

    ... External link, please review our exit disclaimer . Subscribe Gene Tests May Improve Therapy for Endometrial Cancer By analyzing genes in hundreds of endometrial tumors, scientists identified details ...

  14. Genomic characterization of recurrent high-grade astroblastoma.

    PubMed

    Bale, Tejus A; Abedalthagafi, Malak; Bi, Wenya Linda; Kang, Yun Jee; Merrill, Parker; Dunn, Ian F; Dubuc, Adrian; Charbonneau, Sarah K; Brown, Loreal; Ligon, Azra H; Ramkissoon, Shakti H; Ligon, Keith L

    2016-01-01

    Astroblastomas are rare primary brain tumors, diagnosed based on histologic features. Not currently assigned a WHO grade, they typically display indolent behavior, with occasional variants taking a more aggressive course. We characterized the immunohistochemical characteristics, copy number (high-resolution array comparative genomic hybridization, OncoCopy) and mutational profile (targeted next-generation exome sequencing, OncoPanel) of a cohort of seven biopsies from four patients to identify recurrent genomic events that may help distinguish astroblastomas from other more common high-grade gliomas. We found that tumor histology was variable across patients and between primary and recurrent tumor samples. No common molecular features were identified among the four tumors. Mutations commonly observed in astrocytic tumors (IDH1/2, TP53, ATRX, and PTEN) or ependymoma were not identified. However one case with rapid clinical progression displayed mutations more commonly associated with GBM (NF1(N1054H/K63)*, PIK3CA(R38H) and ERG(A403T)). Conversely, another case, originally classified as glioblastoma with nine-year survival before recurrence, lacked a GBM mutational profile. Other mutations frequently seen in lower grade gliomas (BCOR, BCORL1, ERBB3, MYB, ATM) were also present in several tumors. Copy number changes were variable across tumors. Our findings indicate that astroblastomas have variable growth patterns and morphologic features, posing significant challenges to accurate classification in the absence of diagnostically specific copy number alterations and molecular features. Their histopathologic overlap with glioblastoma will likely confound the observation of long-term GBM "survivors". Further genomic profiling is needed to determine whether these tumors represent a distinct entity and to guide management strategies. PMID:27425854

  15. Collapse in High-Grade Stenosis during Pulsatile Flow Experiments

    NASA Astrophysics Data System (ADS)

    Kobayashi, Shunichi; Tang, Dalin; Ku, David N.

    It has been hypothesized that blood flow through high grade stenotic arteries may produce conditions in which elastic flow choking may occur. The development of atherosclerotic plaque fracture may be exacerbated by the compressive stresses during collapse. This study explored the effects of pulsatile flow on stenotic flow collapse. Pulsatile flow was produced using a gear pump controlled by a digitized physiologic waveform. Upstream and downstream mean pressures and pulsatile flow rates were measured and digitized. An improved model of arterial stenosis was created using an elastomer with an incremental modulus of elasticity matched to a bovine carotid artery in the relevant range of collapse. Additionally, the model retained a very thick wall in the stenotic region similar to arterial disease. Flow choking was observed for pulsatile pressure drops close to those previously reported for steady flow. The phase difference between flow rate and pressure between upstream and downstream of the stenosis occurred by the compliance of tube and stenosis resistance. For 80% nominal stenosis by diameter and 100+/-30mmHg upstream pressure, collapse occurred for average pulsatile pressure drops of 93mmHg. Pulsatile flow experiments in this model revealed the range of conditions for the flow choking and the paradoxical collapse of the stenosis during systole with expansion during diastole. The stenosis severity was dynamic through the pulse cycle and was significantly greater under flow than the nominal severity. The results indicate that flow choking and stenotic compression may be significant in thick-walled arterial stenoses subjected to pulsatile flow.

  16. Nimotuzumab in combination with radiotherapy in high grade glioma patients

    PubMed Central

    Solomon, Maria Teresa; Miranda, Nederlay; Jorrín, Eugenia; Chon, Ivonne; Marinello, Jorge Juan; Alert, José; Lorenzo-Luaces, Patricia; Crombet, Tania

    2014-01-01

    Nimotuzumab, a humanized antibody targeting epidermal growth factor receptor, has potent anti-proliferative, anti-angiogenic, and pro-apoptotic effects in vitro and in vivo. It also reduces the number of radio-resistant CD133+ glioma stem cells. The antibody has been extensively evaluated in patients with advanced head and neck, glioma, lung, esophageal, pancreatic, and gastric cancer. In this single institution experience, 35 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with irradiation and 200 mg doses of nimotuzumab. The first 6 doses were administered weekly, together with radiotherapy, and then treatment continued every 21 days until 1 year. The median number of doses was 12, and the median cumulative dose was thus 2400 mg of nimotuzumab. The most frequent treatment-related toxicities were increase in liver function tests, fever, nausea, anorexia, asthenia, dizziness, and tremors. These adverse reactions were classified as mild and moderate. The median survival time was 12.4 mo or 27.0 mo for patients with GBM or AA patients, respectively, who received curative-intent radiotherapy in combination with the antibody. The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy. We have thus confirmed that nimotuzumab is a very well-tolerated drug, lacking cumulative toxicity after maintenance doses. This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients. PMID:24521695

  17. Endometrial aspiration cytology in gynecological disorders

    PubMed Central

    Jadhav, Meenal V.; Phatke, Anjali S.; Kadgi, Nalini Vinayak; Rane, Sharda R.; Kulkarni, Kalpana K.

    2016-01-01

    Context: Endometrial aspiration is not a popular modality for the study of the endometrium despite its simplicity and potential utility. Aim: The present study was aimed at evaluating the utility of endometrial aspiration in various gynecological disorders. Materials and Methods: In this diagnostic accuracy study, 55 prospectively registered women with various gynecological disorders were evaluated clinically and subjected to endometrial aspiration cytology and study of endometrial histology. Endometrial aspiration was performed by infant feeding tube in 10 cases and intra cath cannula in 45 cases. The slides were stained with rapid Papanicolaou (PAP) stain and Leishman stain. Results: Endometrial aspiration cytology showed 90% and 94.6% sampling adequacy with infant feeding tube and intra cath cannula, respectively. Intra cath cannula was very convenient to handle and superior to infant feeding tube in aspirating the endometrium. Of the two stains used, rapid PAP stain was less time-consuming and superior to Leishman stain in studying the nuclear details. Leishman stain was helpful in detecting cytoplasmic vacuoles of secretory endometrium. Overall diagnostic accuracy of endometrial cytology was 90.4% while that for morphological hormonal evaluation was 97.6%. It enjoyed a sensitivity of 91.66%, a specificity of 88.23%, positive predictive value of 94.28%, and negative predictive value of 83.33%. Conclusion: Intra cath cannula emerged as an inexpensive, effective, and convenient device for endometrial aspiration. Endometrial aspiration proved to be a fairly effective, simple, and informative diagnostic modality. PMID:27011435

  18. Genomic Characterization of High-Grade Serous Ovarian Cancer: Dissecting Its Molecular Heterogeneity as a Road Towards Effective Therapeutic Strategies.

    PubMed

    Mittempergher, Lorenza

    2016-07-01

    High-grade serous ovarian carcinoma (HGSOC) accounts for the majority of the ovarian cancer deaths, but over the last years little improvement in overall survival has been achieved. HGSOC is a molecularly and clinically heterogeneous disease. At genomic level, it represents a C-class malignancy having frequent gene losses (NF1, RB1, PTEN) and gains (CCNE1, MYC). HGSOC shows a simple mutational profile with TP53 nearly always mutated and with other genes mutated at low frequency. Importantly, 50 % of all HGSOCs have genetic features indicating a homologous recombination (HR) deficiency. HR deficient tumors are highly sensitive to PARP inhibitor anticancer agents, which exhibit synthetic lethality with a defective HR pathway. Transcriptionally, HGSOCs can be grouped into different molecular subtypes with distinct biology and prognosis. Molecular stratification of HGSOC based on these genomic features may result in improved therapeutic strategies. PMID:27241520

  19. Post-ablation lymphocytic esophagitis in Barrett esophagus with high grade dysplasia or intramucosal carcinoma.

    PubMed

    Kissiedu, Juliana; Thota, Prashanthi N; Gohel, Tushar; Lopez, Rocio; Gordon, Ilyssa O

    2016-06-01

    In patients who have undergone ablation therapy for treatment of Barrett's esophagus with dysplasia, histologic features of eosinophilic esophagitis, but not lymphocytic esophagitis, have been described. We evaluated for histologic evidence of eosinophilic esophagitis and lymphocytic esophagitis and correlated with endoscopic findings in this population. A single-institution Barrett's esophagus registry was searched for patients who had received radiofrequency ablation, cryotherapy, or both for treatment of Barrett's esophagus with dysplasia. Clinical and endoscopic data were collected and biopsies were reviewed for inflammation and reactive changes at three time points: pre-intervention, first surveillance after ablation therapy, and most recent surveillance. Of the 173 patients initially identified, 102 met the inclusion criteria. Intraepithelial eosinophils were increased at first surveillance (60%, P=0.096) and last surveillance (69%, P=0.048) compared with pre-intervention (50%), although histologic evidence of post-ablation eosinophilic esophagitis was not significant. Prevalence of lymphocytic esophagitis was significantly higher at first surveillance (17%, P=0.02) and at last surveillance (43%, P<0.001), compared with pre-intervention (7%). Smoking, hyperlipidemia, and cryotherapy were identified as independent risk factors for developing histologic lymphocytic esophagitis. This is the first report that histologic evidence of lymphocytic esophagitis increased over time in patients undergoing ablation for Barrett's esophagus with dysplasia. Though the pathophysiology of lymphocytic esophagitis remains unknown, patients in our study with a history of smoking, hyperlipidemia, or cryotherapy were more likely to develop post-ablation lymphocytic esophagitis. PMID:26965580

  20. High-grade lung adenocarcinoma with fetal lung-like morphology: clinicopathologic, immunohistochemical, and molecular analyses of 17 cases.

    PubMed

    Morita, Shigeki; Yoshida, Akihiko; Goto, Akiteru; Ota, Satoshi; Tsuta, Koji; Yokozawa, Karin; Asamura, Hisao; Nakajima, Jun; Takai, Daiya; Mori, Masaya; Oka, Teruaki; Tamaru, Junichi; Itoyama, Shinji; Furuta, Koh; Fukayama, Masashi; Tsuda, Hitoshi

    2013-06-01

    Low-grade lung adenocarcinoma of fetal lung type, which is well characterized by its unique clinicopathologic and molecular features, is recognized as a distinct variant of lung cancer. In contrast, high-grade lung adenocarcinoma with fetal lung-like morphology (HG-LAFM) has not been studied widely. To characterize this subset better, we analyzed 17 high-grade adenocarcinomas with at least focal component resembling a developing epithelium in the pseudoglandular phase of the fetal lung. These rare (ca. 0.4%) carcinomas occurred predominantly in elderly men with a heavy smoking history, who showed elevated serum α-fetoprotein in 4 of 5 cases tested. Histologic examination revealed a fetal lung-like component as a focal finding accounting for 5% to 60% of the total tumor volume. It was invariably admixed with tissues having a morphology not resembling that of a fetal lung. A coexisting non-fetal lung-like element was quite heterogenous in appearance, showing various growth patterns. However, clear-cell (88%), hepatoid (29%), and large cell neuroendocrine carcinoma (24%) histology seemed overrepresented. HG-LAFM was characterized immunohistochemically by frequent expression of α-fetoprotein (41%), glypican-3 (88%), SALL-4 (59%), neuroendocrine markers (82%), CDX-2 (35%), and p53 (65%). HG-LAFM was molecularly heterogenous in that EGFR or KRAS mutation was observed in 22% of cases tested for both. Our data indicate that HG-LAFMs might form a coherent subgroup of lung adenocarcinomas. However, the uniformly focal nature of the fetal lung-like element, widely diverse coexisting non-fetal lung-like histology, and inhomogenous molecular profiles lead us to believe that HG-LAFM is best regarded as a morphologic pattern showing characteristic association with several clinicopathologic parameters rather than a specific tumor entity. PMID:23629442

  1. Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report

    PubMed Central

    Chung, Soo-Ho

    2016-01-01

    Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for less than 3% of all endometrial cancers. It is presumed that clear cell carcinomas are of Müllerian duct origin, and an association with exposure to diethylstilbestrol (DES) or other nonsteroidal follicle stimulating hormones has been described. We report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Under the impression of an endometrial mass, we performed a laparoscopic operation. Pathologic results showed clear cell carcinoma of the endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and the rectal shelf mass was clear cell carcinoma. We report the case with a brief review of the relevant literature. PMID:27617248

  2. Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report.

    PubMed

    Chung, Soo-Ho; Park, Jung-Woo

    2016-08-01

    Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for less than 3% of all endometrial cancers. It is presumed that clear cell carcinomas are of Müllerian duct origin, and an association with exposure to diethylstilbestrol (DES) or other nonsteroidal follicle stimulating hormones has been described. We report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Under the impression of an endometrial mass, we performed a laparoscopic operation. Pathologic results showed clear cell carcinoma of the endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and the rectal shelf mass was clear cell carcinoma. We report the case with a brief review of the relevant literature. PMID:27617248

  3. Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer

    SciTech Connect

    Lin, Lilie L.; Grigsby, Perry W. . E-mail: pgrigsby@wustl.edu; Powell, Matthew A.; Mutch, David G.

    2005-10-01

    Purpose: The aim of our study was to assess prognostic factors and overall survival after salvage radiotherapy for patients who had endometrial carcinoma and who experienced an isolated vaginal recurrence. Methods and Materials: We reviewed the records of 50 patients treated at our institution between 1967 and 2003 for an isolated vaginal recurrence of endometrial carcinoma. Initial treatment for endometrial carcinoma was definitive surgery in 49 patients and definitive radiotherapy in 1 patient. The median time from initial diagnosis of endometrial carcinoma to recurrence was 25 months (range, 4-179 months). Three patients (6%) received external-beam radiotherapy alone, 8 patients (16%) received brachytherapy only, and 39 patients (78%) received combined external-beam radiation therapy and brachytherapy. Median dose of radiation to the recurrence was 60 Gy (range, 16-85 Gy). Overall survival was calculated by the Kaplan-Meier method. Endpoints were measured from the date of diagnosis of the vaginal recurrence. Median follow-up of survivors after recurrence was 53 months (range, 8-159 months). Results: The 5-year and 10-year disease-free and overall survivals were 68% and 55%, and 53% and 40%, respectively. On multivariate analysis, age (p = 0.0242), Grade 1 or 2 vs. Grade 3 tumor (p = 0.002), and size of recurrence (p < 0.001) were significant predictors of overall survival. All patients who had Grade 3 disease were dead by 3.6 years from the time of recurrence. Five patients experienced a Grade 3 or 4 complication. Conclusions: Patients treated with radiotherapy for an isolated vaginal recurrence can be cured in over 50% the cases. Radiotherapy is well tolerated, with a low risk of complications. Factors predictive of overall survival include tumor grade, patient age at recurrence, and tumor size.

  4. Etiologic Heterogeneity in Endometrial Cancer: Evidence from a Gynecologic Oncology Group Trial

    PubMed Central

    Brinton, Louise A.; Felix, Ashley S.; McMeekin, D. Scott; Creasman, William T.; Sherman, Mark E.; Mutch, David; Cohn, David E.; Walker, Joan L.; Moore, Richard G.; Downs, Levi S.; Soslow, Robert A.; Zaino, Richard

    2014-01-01

    Objective Although the epidemiology of typical endometrial carcinomas (grades 1–2 endometrioid or Type I) is well established, less is known regarding higher grade endometrioid or non-endometrioid carcinomas (Type II). Within a large Gynecologic Oncology Group trial (GOG-210), which included central pathology review, we investigated the etiologic heterogeneity of endometrial cancers by comparing risk factors for different histologic categories. Methods Based on epidemiologic questionnaire data, risk factor associations, expressed as odds ratios (OR) with 95% confidence intervals (CI), were estimated comparing grade 3 endometrioid and Type II cancers (including histologic subtypes) to grades 1–2 endometrioid cancers. Results Compared with 2,244 grades 1–2 endometrioid cancers, women with Type II cancers (321 serous, 141 carcinosarcomas, 77 clear cell, 42 mixed epithelial with serous or clear cell components) were older; more often non-white, multiparous, current smokers; and less often obese. Risk factors for grade 3 endometrioid carcinomas (n=354) were generally similar to those identified for Type II cancers, although patients with grade 3 endometrioid tumors more often had histories of breast cancer without tamoxifen exposure while those with Type II tumors were more frequently treated with tamoxifen. Patients with serous cancers and carcinosarcomas more frequently had breast cancer histories with tamoxifen treatment compared to patients with other tumors. Conclusions Risk factors for aggressive endometrial cancers, including grade 3 endometrioid and non-endometrioid tumors, appear to differ from lower grade endometrioid carcinomas. Our findings support etiologic differences between Type I and II endometrial cancers as well as additional heterogeneity within Type II cancers. PMID:23485770

  5. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    ClinicalTrials.gov

    2016-07-05

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  6. Endometrial polyps in 2 African pygmy hedgehogs

    PubMed Central

    2005-01-01

    Abstract Reports of spontaneously occurring endometrial polyps in animals are rare and have only involved a few species. This report is intended to advise veterinarians that older African pygmy hedgehogs may develop endometrial polyps and that these lesions can be a cause of bloody vaginal discharge, sometimes interpreted as hematuria. PMID:16048013

  7. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1100 Endometrial brush. (a) Identification....

  8. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial aspirator. 884.1060 Section 884.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1060 Endometrial aspirator....

  9. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endometrial aspirator. 884.1060 Section 884.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1060 Endometrial aspirator....

  10. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1185 Endometrial washer. (a) Identification....

  11. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1185 Endometrial washer. (a) Identification....

  12. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1100 Endometrial brush. (a) Identification....

  13. Diagnosis and Management of Endometrial Cancer.

    PubMed

    Braun, Michael M; Overbeek-Wager, Erika A; Grumbo, Robert J

    2016-03-15

    Endometrial cancer is the most common gynecologic malignancy. It is the fourth most common cancer in women in the United States after breast, lung, and colorectal cancers. Risk factors are related to excessive unopposed exposure of the endometrium to estrogen, including unopposed estrogen therapy, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility or failure to ovulate, and polycystic ovary syndrome. Additional risk factors are increasing age, obesity, hypertension, diabetes mellitus, and hereditary nonpolyposis colorectal cancer. The most common presentation for endometrial cancer is postmenopausal bleeding. The American Cancer Society recommends that all women older than 65 years be informed of the risks and symptoms of endometrial cancer and advised to seek evaluation if symptoms occur. There is no evidence to support endometrial cancer screening in asymptomatic women. Evaluation of a patient with suspected disease should include a pregnancy test in women of childbearing age, complete blood count, and prothrombin time and partial thromboplastin time if bleeding is heavy. Most guidelines recommend either transvaginal ultrasonography or endometrial biopsy as the initial study. The mainstay of treatment for endometrial cancer is total hysterectomy with bilateral salpingo-oophorectomy. Radiation and chemotherapy can also play a role in treatment. Low- to medium-risk endometrial hyperplasia can be treated with nonsurgical options. Survival is generally defined by the stage of the disease and histology, with most patients at stage I and II having a favorable prognosis. Controlling risk factors such as obesity, diabetes, and hypertension could play a role in the prevention of endometrial cancer. PMID:26977831

  14. Identification of appropriate cone length to avoid positive cone margin in high grade cervical intraepithelial neoplasia

    PubMed Central

    Tsuda, Naotake; Nishio, Shin; Ushijima, Kimio

    2016-01-01

    Objective To identify key factors for predicting positive cone margin and appropriate cone length. Methods We retrospectively reviewed the margin status of patients who received conization with high grade cervical intraepithelial neoplasia, along with other factors such as patient age, parity, preoperative cytology, size of disease, type of transformation zone, and cone length from patient records. Cut-off value of cone length was analyzed in women younger than 40 years old because we design conization with minimum length especially for women who wish for future pregnancy. Cut-off value of cone length was defined as length corresponds to estimated probability of positive cone margin equal to 0.1 by logistic regression analysis with variables selected by stepwise methods. Results Among 300 patients, 75 patients had positive cone margin. Multivariable analysis revealed that squamous cell carcinoma at preoperative cytology (p=0.001), 2 or more quadrant disease (p=0.011), and shorter cone length (p<0.001) were risk factors for positive cone margin. Stepwise methods identified cone length and size of lesion as important variables. With this condition, cut-off value of cone length was estimated as 15 mm in single quadrant disease and 20 mm in 2 or more quadrant disease, respectively. Conclusion We identified the independent risk factors of positive cone margin and identified the cut-off value of cone length to avoid positive cone margin in women younger than 40 years old. Conization should be performed not only according to colposcopic findings including type of transformation zone but size of disease and cone length. PMID:27401478

  15. High frequency of the X-chromosome inactivation in young female patients with high-grade glioma

    PubMed Central

    2013-01-01

    Background Gliomas are common tumors and high-grade ones account for 62% of primary malignant brain tumors. Though current evidence have suggested that inherited risks play a role in glioma susceptibility, it was conveyed that glioma was such a complex disease, and the direct genetic contribution to glioma risk factors and its relation to other factors should be discussed more deeply. X-chromosome inactivation (XCI) is the mechanism by which gene dosage equivalence is achieved between female mammals with two X chromosomes and male mammals with a single X chromosome. As skewed XCI has been linked to development of some solid tumors, including ovarian, breast, and pulmonary and esophageal carcinomas, it is challenging to elucidate the relation of skewed XCI to high-grade gliomas development. Objective The present study aimed to determine the general concordance between XCI pattern in blood cells and brain tissues, and SXCI frequencies in female patients with high-grade glioma compared to healthy controls. Methods 1,103 Chinese females without a detectable tumor and 173 female high-grade glioma patients, were detected in the study. Normal brain tissues surrounding the lesions in gliomas were obtained from 49 patients among the 173 ones, with the microdissection using a laser microdissection microscope Genomic DNA was extracted from the peripheral blood cells and the normal brain tissues from the subjects. Exon 1 of androgen receptor (AR) gene was amplified, and its products of different alleles were resolved on denaturing polyacrylamide gels and visualized after silver staining. The corrected ratios (CR) of the products before and after HpaII digestion were calculated. Results Occurrence of SXCI was detected in both the patients and controls at similar frequencies. However, the phenomenon, as defined as CR ≥ 3, was more frequent in the patients aging ≤40 (23.6%) compared to the corresponding reference group (5.1%, P <0.0001). When CR ≥ 10 was adopted

  16. Evaluation of endometrial cancer epidemiology in Romania

    PubMed Central

    Bohîlțea, RE; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, LC

    2015-01-01

    Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women’s genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data. PMID:25866582

  17. Evaluation of endometrial cancer epidemiology in Romania.

    PubMed

    Bohîlțea, R E; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, L C

    2015-01-01

    Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women's genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data. PMID:25866582

  18. An update of the classical Bokhman's dualistic model of endometrial cancer

    PubMed Central

    Wilczyński, Miłosz; Danielska, Justyna

    2016-01-01

    According to the classical dualistic model introduced by Bokhman in 1983, endometrial cancer (EC) is divided into two basic types. The prototypical histological type for type I and type II of EC is endometrioid carcinoma and serous carcinoma, respectively. The traditional classification is based on clinical, endocrine and histopathological features, however, it sometimes does not reflect the full heterogeneity of EC. New molecular evidence, supported by clinical diversity of the cancer, indicates that the classical dualistic model is valid only to some extent. The review updates a mutational diversity of EC, introducing a new molecular classification of the tumour in regard to data presented by The Cancer Genome Atlas Research Network (TGCA).

  19. Targeted Screening With Combined Age- and Morphology-Based Criteria Enriches Detection of Lynch Syndrome in Endometrial Cancer.

    PubMed

    Lin, Douglas I; Hecht, Jonathan L

    2016-06-01

    Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients <50 years; (2) patients of any age with tumors showing features of microsatellite instability (lower uterine segment-centered tumors, hard to classify carcinomas, increased peritumoral or tumor infiltrating lymphocytes and cases with synchronous ovarian carcinomas); (3) clinician's request based on family or personal history; and (4) ad hoc retrospective testing based on the established criteria on patients discovered on follow-up visits. By using a targeted screening approach in a 4.5-year period, approximately 2.1% of endometrial cancers (7 of 328) were potentially associated with Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening. PMID:26842347

  20. Trop-2 overexpression in poorly differentiated endometrial endometrioid adenocarcinoma: Implications for immunotherapy with hRS7, a humanized anti-Trop-2 monoclonal antibody

    PubMed Central

    Bignotti, Eliana; Ravaggi, Antonella; Romani, Chiara; Falchetti, Marcella; Lonardi, Silvia; Facchetti, Fabio; Pecorelli, Sergio; Varughese, Joyce; Cocco, Emiliano; Bellone, Stefania; Schwartz, Peter E.; Rutherford, Thomas J.; Santin, Alessandro D.

    2011-01-01

    Objective We evaluated the expression of human trophoblast cell-surface marker (Trop-2) in endometrial endometrioid carcinoma (EEC) and the potential application of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a therapeutic agent against poorly-differentiated EEC. Methods Trop-2 expression was evaluated by immunohistochemistry in 131 EEC with different degrees of differentiation and 32 normal endometrial controls (NEC). Trop-2 expression was also evaluated by real-time polymerase-chain-reaction (qRT-PCR) and flow cytometry in 3 primary EEC cell lines derived from patients harboring poorly-differentiated EEC. Finally, sensitivity of G3 EEC cell lines to hRS7 antibody-dependent cellular-cytotoxicity (ADCC) was tested in standard 5-hours 51Cr-release assays. Results Trop-2 expression was detected in 126 of 131 (96.2%) EEC samples. Tumor tissues showed markedly increased Trop-2 positivity as compared to NEC (p=0.001). Trop-2 expression was significantly higher in all grades of EEC vs. NEC. G3 tumors displayed significantly stronger Trop-2 immunostaining compared to G1 EEC (p=0.01). High Trop-2 expression by qRT-PCR and flow cytometry was found in one G3 EEC primary cell line (EEC-ARK-1). Unlike Trop-2-negative EEC cell lines, EEC-ARK-1 was found highly sensitive to hRS7-mediated ADCC in vitro (range of killing: 33.9% to 50.6%) (p=0.004). Human serum did not significantly inhibit hRS7-mediated-cytotoxicity against EEC-ARK-1 (p= 0.773). Conclusions Trop-2 is highly expressed in EEC and its expression is significantly higher in poorly-differentiated EEC when compared to well-differentiated EEC. Primary G3 EEC overexpressing Trop-2 are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for the treatment of high-grade EEC refractory to standard treatment modalities. PMID:21892093

  1. Prognostic Implication of Preoperative Behavior Changes in Patients with Primary High-Grade Meningiomas

    PubMed Central

    2014-01-01

    High-grade meningiomas are rare extra-axial tumors, frequently causing brain invasion and prominent brain edema. Patients harboring high-grade meningiomas occasionally present with behavior changes. Data about frequency and prognostic importance of preoperative behavior changes in patients with high-grade meningiomas is missing. 86 patients with primary high-grade meningiomas were analyzed. Statistical analysis was performed to determine correlation of preoperative behavior changes with tumor location, preoperative brain edema, tumor cleavability, tumor grade, Ki67 proliferation index, and microscopic brain invasion. Survival analysis was performed. 30 (34.9%) patients presented with preoperative behavior changes. These changes were more frequent with male patients (P = 0.066) and patients older than 55 years (P = 0.018). They correlated with frontal location (P = 0.013), tumor size (P = 0.023), microscopic brain invasion (P = 0.015), and brain edema (P = 0.006). Preoperative behavior changes did not correlate with duration of symptoms, tumor cleavability, tumor malignancy grade, and Ki67 proliferation index. They were not significantly related to overall survival or recurrence-free survival of patients with primary high-grade meningiomas. Preoperative behavior changes are frequent in patients harboring primary high-grade meningiomas. They correlate with tumor size, microscopic brain invasion, and brain edema. Preoperative behavior changes do not predict prognosis in patients with primary high-grade meningiomas. PMID:24578632

  2. High levels of Nrf2 determine chemoresistance in type II endometrial cancer

    PubMed Central

    Jiang, Tao; Chen, Ning; Zhao, Fei; Wang, Xiao-Jun; Kong, Beihua; Zheng, Wenxin; Zhang, Donna D.

    2010-01-01

    Type II endometrial cancer, which mainly presents as serous and clear cell types, has proved to be the most malignant and recurrent carcinoma among various female genital malignancies. The transcription factor, Nrf2, was first described as having chemopreventive activity. Activation of the Nrf2-mediated cellular defense response protects cells against the toxic and carcinogenic effects of environmental insults by upregulating an array of genes that detoxify reactive oxygen species (ROS) and restore cellular redox homeostasis. However, the cancer-promoting role of Nrf2 has recently been revealed. Nrf2 is constitutively upregulated in several types of human cancer tissues and cancer cell lines. Furthermore, inhibition of Nrf2 expression sensitizes cancer cells to chemotherapeutic drugs. In this study, the constitutive level of Nrf2 was compared in different types of human endometrial tumors. It was found that Nrf2 was highly expressed in endometrial serous carcinoma (ESC), whereas complex hyperplasia (CH) and endometrial endometrioid carcinoma (EEC) had no or marginal expression of Nrf2. Likewise, the ESC derived SPEC-2 cell line had a higher level of Nrf2 expression and was more resistant to the toxic effects of cisplatin and paclitaxel than that of the Ishikawa cell line, which was generated from EEC. Silencing of Nrf2 rendered SPEC-2 cells more susceptible to chemotherapeutic drugs while it had a limited effect on Ishikawa cells. Inhibition of Nrf2 expression by overexpressing Keap1 sensitized SPEC-2 cells or SPEC-2-derived xenografts to chemotherapeutic treatments using both cell culture and SCID mouse models. Collectively, we provide a molecular basis for the use of Nrf2 inhibitors to increase the efficacy of chemotherapeutic drugs and to combat chemoresistance, the biggest obstacle in chemotherapy. PMID:20530669

  3. Sonohysterography: a technique for endometrial evaluation.

    PubMed

    Cullinan, J A; Fleischer, A C; Kepple, D M; Arnold, A L

    1995-05-01

    Sonohysterography involves the instillation of sterile saline under continuous sonographic visualization to assess the endometrial cavity. The technique is most useful for evaluating women with fertility problems, postmenopausal bleeding, or an abnormal endometrial interface as seen at baseline sonography. The procedure is performed with saline instilled into the endometrial cavity through a 5-F pediatric feeding tube or a hysterosalpingography or insemination catheter. In the normal uterus, the endometrium appears symmetric, surrounding the anechoic, saline-distended endometrial cavity. Adhesions appear as bridging bands of tissue that distort the uterine cavity or as very thin, undulating membranes, best seen at real-time examination. An intracavitary polyp is seen surrounded by anechoic fluid, with the point of attachment and thickness of the stalk clearly demonstrated. The location of leiomyomas can be determined: Intramural lesions do not distort the endometrial cavity, whereas submucosal lesions often do, with the overlying normal layer of endometrium clearly seen. In women with abnormal bleeding, focal areas of asymmetric endometrial thickening can be identified. Sonohysterography allows differentiation of intracavitary, endometrial, and submucosal abnormalities without the use of ionizing radiation or contrast agents. PMID:7624559

  4. Endometrial receptivity array: Clinical application.

    PubMed

    Mahajan, Nalini

    2015-01-01

    Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER. PMID:26538853

  5. Endometrial receptivity array: Clinical application

    PubMed Central

    Mahajan, Nalini

    2015-01-01

    Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER. PMID:26538853

  6. G protein-coupled estrogen receptor-selective ligands modulate endometrial tumor growth.

    PubMed

    Petrie, Whitney K; Dennis, Megan K; Hu, Chelin; Dai, Donghai; Arterburn, Jeffrey B; Smith, Harriet O; Hathaway, Helen J; Prossnitz, Eric R

    2013-01-01

    Endometrial carcinoma is the most common cancer of the female reproductive tract. GPER/GPR30 is a 7-transmembrane spanning G protein-coupled receptor that has been identified as the third estrogen receptor, in addition to ERα and ERβ. High GPER expression is predictive of poor survival in endometrial and ovarian cancer, but despite this, the estrogen-mediated signaling pathways and specific estrogen receptors involved in endometrial cancer remain unclear. Here, employing ERα-negative Hec50 endometrial cancer cells, we demonstrate that GPER mediates estrogen-stimulated activation of ERK and PI3K via matrix metalloproteinase activation and subsequent transactivation of the EGFR and that ER-targeted therapeutic agents (4-hydroxytamoxifen, ICI182,780/fulvestrant, and Raloxifene), the phytoestrogen genistein, and the "ERα-selective" agonist propylpyrazole triol also function as GPER agonists. Furthermore, xenograft tumors of Hec50 cells yield enhanced growth with G-1 and estrogen, the latter being inhibited by GPER-selective pharmacologic antagonism with G36. These results have important implications with respect to the use of putatively ER-selective ligands and particularly for the widespread long-term use of "ER-targeted" therapeutics. Moreover, our findings shed light on the potential mechanisms of SERM/SERD side effects reported in many clinical studies. Finally, our results provide the first demonstration that pharmacological inhibition of GPER activity in vivo prevents estrogen-mediated tumor growth. PMID:24379833

  7. G Protein-Coupled Estrogen Receptor-Selective Ligands Modulate Endometrial Tumor Growth

    PubMed Central

    Petrie, Whitney K.; Dennis, Megan K.; Dai, Donghai; Arterburn, Jeffrey B.; Smith, Harriet O.; Hathaway, Helen J.; Prossnitz, Eric R.

    2013-01-01

    Endometrial carcinoma is the most common cancer of the female reproductive tract. GPER/GPR30 is a 7-transmembrane spanning G protein-coupled receptor that has been identified as the third estrogen receptor, in addition to ERα and ERβ. High GPER expression is predictive of poor survival in endometrial and ovarian cancer, but despite this, the estrogen-mediated signaling pathways and specific estrogen receptors involved in endometrial cancer remain unclear. Here, employing ERα-negative Hec50 endometrial cancer cells, we demonstrate that GPER mediates estrogen-stimulated activation of ERK and PI3K via matrix metalloproteinase activation and subsequent transactivation of the EGFR and that ER-targeted therapeutic agents (4-hydroxytamoxifen, ICI182,780/fulvestrant, and Raloxifene), the phytoestrogen genistein, and the “ERα-selective” agonist propylpyrazole triol also function as GPER agonists. Furthermore, xenograft tumors of Hec50 cells yield enhanced growth with G-1 and estrogen, the latter being inhibited by GPER-selective pharmacologic antagonism with G36. These results have important implications with respect to the use of putatively ER-selective ligands and particularly for the widespread long-term use of “ER-targeted” therapeutics. Moreover, our findings shed light on the potential mechanisms of SERM/SERD side effects reported in many clinical studies. Finally, our results provide the first demonstration that pharmacological inhibition of GPER activity in vivo prevents estrogen-mediated tumor growth. PMID:24379833

  8. Occupational Risk Factors for Endometrial Cancer among Textile Workers in Shanghai, China

    PubMed Central

    Wernli, Karen J.; Ray, Roberta M.; Gao, Dao Li; Fitzgibbons, E. Dawn; Camp, Janice E.; Astrakianakis, George; Seixas, Noah; Li, Wenjin; De Roos, Anneclaire J.; Feng, Ziding; Thomas, David B.; Checkoway, Harvey

    2008-01-01

    Objective A case-cohort study was conducted to investigate associations between occupational exposures and endometrial cancer nested within a large cohort of textile workers in Shanghai, China. Methods The study included 176 incident endometrial cancer cases diagnosed from 1989-1998 and a randomly-selected age-stratified reference subcohort (n=3061). Study subjects' complete work histories were linked to a job-exposure matrix developed specifically for the textile industry to assess occupational exposures. Hazard ratios (HR) and 95 percent confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design, adjusting for age at menarche and a composite variable of gravidity and parity. Results An increased risk of endometrial cancer was detected among women who had worked for ≥10 years or more in silk production (HR=3.8, 95% CI 1.2-11.8) and had exposure to silk dust (HR=1.7, 95% CI 0.9-3.4). Albeit with few exposed women (2 cases and 8 subcohort women), there was a 7.4-fold increased risk associated with ≥10 years of silica dust exposure (95% CI 1.4-39.7). Conclusions The findings suggest that some textile industry exposures might play a role in endometrial carcinoma and should be further replicated in other occupational settings. PMID:18626909

  9. Siegesbeckia orientalis Extract Inhibits TGFβ1-Induced Migration and Invasion of Endometrial Cancer Cells.

    PubMed

    Chang, Chi-Chang; Ling, Xue-Hua; Hsu, Hsia-Fen; Wu, Jing-Mei; Wang, Chao-Ping; Yang, Jyh-Ferng; Fang, Li-Wen; Houng, Jer-Yiing

    2016-01-01

    Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE) on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor β (TGFβ). The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFβ1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFβ1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors. PMID:27527140

  10. View looking northwest toward HIghGrade Ore Bin and Concentrate Bin ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View looking northwest toward HIgh-Grade Ore Bin and Concentrate Bin - Kennecott Copper Corporation, Concentration Mill, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  11. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors.

    PubMed

    Bleeker, Fonnet E; Lamba, Simona; Leenstra, Sieger; Troost, Dirk; Hulsebos, Theo; Vandertop, W Peter; Frattini, Milo; Molinari, Francesca; Knowles, Margaret; Cerrato, Aniello; Rodolfo, Monica; Scarpa, Aldo; Felicioni, Lara; Buttitta, Fiamma; Malatesta, Sara; Marchetti, Antonio; Bardelli, Alberto

    2009-01-01

    Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 (IDH1(R132)) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1(R132) residue were detected in 20% (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1(R132) in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1(R132) are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas. PMID:19117336

  12. Breast cancer susceptibility polymorphisms and endometrial cancer risk: a Collaborative Endometrial Cancer Study

    PubMed Central

    Ahmed, Shahana; O’Mara, Tracy A.; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A.; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P.; Lissowska, Jolanta; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D.P.; Thompson, Deborah J.; Rebbeck, Timothy R.; Strom, Brian L.; Dunning, Alison M.; Easton, Douglas F.; Spurdle, Amanda B.

    2011-01-01

    Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11 928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer. PMID:21965274

  13. Breast cancer susceptibility polymorphisms and endometrial cancer risk: a Collaborative Endometrial Cancer Study.

    PubMed

    Healey, Catherine S; Ahmed, Shahana; O'Mara, Tracy A; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P; Lissowska, Jolanta; Brinton, Louise A; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D P; Thompson, Deborah J; Rebbeck, Timothy R; Strom, Brian L; Dunning, Alison M; Easton, Douglas F; Spurdle, Amanda B

    2011-12-01

    Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11,928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer. PMID:21965274

  14. Armodafinil in Reducing Cancer-Related Fatigue in Patients With High Grade Glioma | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies armodafinil to see how well it works in reducing cancer-related fatigue in patients with high grade glioma. Armodafinil may help relieve fatigue in patients with high grade glioma. |

  15. How do we manage high-grade T1 bladder cancer? Conservative or aggressive therapy?

    PubMed Central

    Kim, Seon-Kyu; Kim, Wun-Jae

    2016-01-01

    High-grade T1 bladder cancer has a poor prognosis due to a higher incidence of recurrence and progression than other nonmuscle invasive bladder cancer; thus patients with high-grade T1 have to be carefully monitored and managed. If patients are diagnosed with high-grade T1 at initial transurethral resection (TUR), a second TUR is strongly recommended regardless of whether muscle layer is present in the specimen because of the possibility of understating due to incomplete resection. Since high-grade T1 disease shows diverse clinical courses, individual approaches are recommended for treatment. In cases with low risk of progression, cystectomy could represent overtreatment and deteriorate quality of life irreversibly, while, in those with high risk, bacillus Calmette-Guérin (BCG) therapy may worsen survival by delaying definitive therapy. Therefore, a strategy for predicting prognosis based on the risk of progression is needed for managing high-grade T1 disease. Molecular risk classifiers predicting the risk of progression and response to BCG may help identify the optimal management of high-grade T1 disease for each individual. PMID:27326407

  16. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo

    PubMed Central

    Saunders, Laura R.; Bankovich, Alexander J.; Anderson, Wade C.; Aujay, Monette A.; Bheddah, Sheila; Black, KristenAnn; Desai, Radhika; Escarpe, Paul A.; Hampl, Johannes; Laysang, Amy; Liu, David; Lopez-Molina, Javier; Milton, Milly; Park, Albert; Pysz, Marybeth A.; Shao, Hui; Slingerland, Brian; Torgov, Michael; Williams, Samuel A.; Foord, Orit; Howard, Philip; Jassem, Jacek; Badzio, Andrzej; Czapiewski, Piotr; Harpole, David H.; Dowlati, Afshin; Massion, Pierre P.; Travis, William D.; Pietanza, M. Catherine; Poirier, J. T.; Rudin, Charles M.; Stull, Robert A.; Dylla, Scott J.

    2016-01-01

    The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3 protein is expressed on the surface of tumor cells but not in normal adult tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo across multiple PDX models. Serial transplantation experiments executed with limiting dilutions of cells provided functional evidence confirming that the lack of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and responses were observed in PDX models initiated from patients with both limited and extensive-stage disease and were independent of their sensitivity to standard-of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3-expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class ADC for the treatment of high-grade pulmonary neuroendocrine tumors. PMID:26311731

  17. A Cell Type Independent Binary Grading System Does Not Significantly Improve Endometrial Biopsy Interpretation.

    PubMed

    Nastic, Denis; Kahlin, Frida; Dahlstrand, Hanna; Carlson, Joseph W

    2016-05-01

    The revised International Federation of Gynecology and Obstetrics (FIGO) grading system is widely accepted as the standard in evaluating endometrial carcinoma on biopsy. Determination of tumor cell type [using the World Health Organization (WHO) diagnostic criteria] and grade (using FIGO) guides surgical approach. Several studies have highlighted discrepancies between biopsy and hysterectomy diagnosis. Recently, a binary grading system was proposed, yielding a low-risk and high-risk assessment but in a cell type independent (CTI) way. No study has assessed its utility in biopsy grading, a situation where this system may be particularly useful. Archived endometrial biopsies from 70 cases of endometrial carcinoma were graded by 3 independent observers using the WHO/FIGO and the CTI grading systems. The overall accuracy, interobserver agreement, and ease of use were assessed. This study found comparable substantial accuracy between the WHO/FIGO and CTI grading systems (κ=0.71 vs. κ=0.69), with the same setbacks in overgrading of 20.9% versus 25.6% of low-risk tumors. The CTI grading system was not superior to the WHO/FIGO grading system in accuracy of subtyping and grading and interobserver reproducibility. Although determination of cell type is difficult, it does not appear that the proposed CTI system confers any significant advantages over existing grading. PMID:26863477

  18. The epidemic of endometrial cancer: a commentary.

    PubMed Central

    Jick, H; Walker, A M; Rothman, K J

    1980-01-01

    Vital statistics show that a rise in incidence of endometrial cancer began in the mid-1960s on the West Coast of the United States. This rise was continuous and reached a peak in 1975. Elsewhere, incidence rates for endometrial cancer rose during the 1970s. It now seems evident that much of the rise in all areas of the country was due to replacement estrogen treatment. We estimated from data obtained from the Commission on Professional and Hospital Activities-Professional Activity Study of Ann Arbor, Michigan, that over 15,000 cases of endometrial cancer were caused by replacement estrogens during the five-year period 1971--1975 alone. This represents one of the largest epidemics of serious iatrogenic disease that has ever occurred in this country. With the substantial fall in estrogen sales starting in January 1976, there has been an associated decline in the incidence rates of endometrial cancer nationwide. PMID:7356090

  19. Role of Progesterone in Endometrial Cancer

    PubMed Central

    Kim, J. Julie; Chapman-Davis, Eloise

    2016-01-01

    Progesterone is a key hormone in the endometrium that opposes estrogen-driven growth. Insufficient progesterone will result in unopposed estrogen action that could lead to the development of endometrial hyperplasia and adenocarcinoma. Although these endometrial neoplasias can regress in response to progestin treatment, this does not occur in all instances. To understand this resistance to progesterone and to improve on existing hormonal therapies, it is imperative that the molecular mechanisms of progesterone action through its receptor be deciphered in endometrial cancer. This review highlights what is known thus far regarding the efficacy of progestin therapy in the clinic and the role of progesterone in endometrial cancer cell behavior and gene regulation. PMID:20104432

  20. Endocrine and paracrine regulation of endometrial angiogenesis.

    PubMed

    Taylor, R N; Lebovic, D I; Hornung, D; Mueller, M D

    2001-09-01

    The human endometrium is a complex tissue comprised of different cell types, including epithelial, stromal, inflammatory, perivascular, and blood vessel cells. The hormonal receptivity and distribution of these cell populations change during the menstrual cycle. Cyclical endometrial growth is dependent on its ability to regenerate a vascular capillary network, which grows in parallel with the proliferation and differentiation of the endometrial lining. Natural hormonal effects on the endometrium and endocrine manipulation of this tissue, in response to the use of exogenous steroid therapies, can affect endometrial capillary proliferation and function, leading to clinical abnormalities of uterine bleeding. We propose that the regulation of endometrial angiogenesis is mediated indirectly via complex interactions among cell types. Our laboratory has focused on a prototypical member of the angiogenic proteins, vascular endothelial growth factor (VEGF)-A. In this paper we present data demonstrating that VEGF-A expression in normal endometrial epithelial and stromal cells and in Ishikawa adenocarcinoma cells is increased by an ovarian steroid, estradiol. Infiltrating immune cells, particularly polymorphonuclear granulocytes, also are sources of VEGF-A. In inflammatory conditions involving the endometrium (e.g., endometriosis), a proinflammatory cytokine, IL-1beta, can mediate neoangiogenesis by inducing VEGF-A gene transcription. Thus, endometrial vascularization is effected by both endocrine and paracrine pathways. PMID:11594532

  1. Circulating Adiponectin and Risk of Endometrial Cancer

    PubMed Central

    Zheng, Qiaoli; Wu, Haijian; Cao, Jiang

    2015-01-01

    Background Adiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer. Methods PubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies. Results A total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found. Conclusions This meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer. PMID:26030130

  2. ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas

    PubMed Central

    2013-01-01

    Background High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas. Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed high-grade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients. Methods Total RNAs extracted from all tumor samples and controls were tested for RNA editing levels (by direct sequencing on cDNA pools) and for ADAR2 mRNA expression (by qRT-PCR). Results A significant loss of ADAR2-editing activity was observed in the newly diagnosed and recurrent astrocytomas in comparison to normal brain. Surprisingly, we found a substantial rescue of ADAR2 editing activity in the relapsed tumor of the only patient showing prolonged survival. Conclusions High-grade astrocytomas display a generalized loss of ADAR2-mediated RNA editing at both diagnosis and relapse. However, a peculiar Case, in complete remission of disease, displayed a total rescue of RNA editing at relapse, intriguingly suggesting ADAR2 activity/expression as a possible marker for long-term survival of patients with high-grade astrocytomas. PMID:23697632

  3. The value of pelvic radiation therapy after hysterectomy for early endometrial cancer.

    PubMed

    Eifel, Patricia J

    2013-10-01

    Although endometrial carcinoma is one of the most common cancers affecting women, most cases are detected at an early stage and are cured with hysterectomy alone. Most recurrences occur in the relatively small subset of patients whose surgical specimens reveal multiple risk factors. Clinicians have sought to define adjuvant treatments that can improve the outcome of treatment for these higher-risk patients. Although randomized trials have demonstrated that radiation therapy improves local control, they have failed to demonstrate an improvement in survival with radiation therapy. In this review, the results and limitations of studies concerning adjuvant radiation therapy and chemotherapy for endometrial cancer will be discussed, focusing on evidence that can help to guide treatment decisions. PMID:24367856

  4. Study establishes basis for genomic classification of endometrial cancers

    Cancer.gov

    A comprehensive genomic analysis of nearly 400 endometrial tumors suggests that certain molecular characteristics – such as the frequency of mutations – could complement current pathology methods and help distinguish between principal types of endometrial

  5. Neuroendocrine carcinoma of the prostate gland

    PubMed Central

    Hoof, Pamela; Tsai-Nguyen, Ginger; Paulson, Scott; Syed, Almas

    2016-01-01

    Small cell prostate carcinoma (SCPC) has a clinical course and prognosis that is markedly different from that of common adenocarcinoma of the prostate. The patient in this case presented with fever of unknown origin, dyspnea, and near spinal cord compression. He was subsequently found to have widely metastatic high-grade neuroendocrine carcinoma of prostatic origin. This case emphasizes that despite the commonality of prostate cancer, there are rare presentations of this common disease. PMID:26722176

  6. Inhibition of CXCR4 and CXCR7 for reduction of cell proliferation and invasion in human endometrial cancer.

    PubMed

    Long, Ping; Sun, Fengyi; Ma, Yingying; Huang, Yu

    2016-06-01

    As one of the most common malignant cancers in female reproductive tract, endometrial cancer accounts for 20-30 % of the most frequent gynecological malignancy, which is originated from endometrial epithelial. The molecular mechanisms for the generation of endometrial cancer are up to now unclear, hindering the development of corresponding therapy. CXCR4 and CXCR7 were receptors of CXCL12 chemokine ligand, which could regulate critical procedures of neoplastic transformation, including proliferation, invasion, and apoptosis of the cells. The messenger RNA (mRNA) and protein expression levels of CXCR4 and CXCR7 in human endometrial adenocarcinoma cancer, as well as in Ishikawa and HEC-1-A cell line, were analyzed by using reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. In order to explore the biological function of CXCR4 and CXCR7 in endometrial tumor, small interference RNAs of CXCR4 and CXCR7 fragments were designed, synthesized, and transfected into Ishikawa and HEC-1-A by using Lipofectamine2000. The influence of RNA interference (RNAi)-mediated silencing CXCR4 and CXCR7 on the cell proliferation was investigated under CCK-8. The invasion assay was performed transwell, and cell apoptosis was tested by FCM. Higher mRNA and protein expression levels of CXCR4 and CXCR7 were investigated in endometrial adenocarcinomas. The expression levels of CXCR4 and CXCR7 could be inhibited by RNA interference, reducing the cell proliferation, invasion in Ishikawa and HEC-1-A cells. In this study, we also observed that treated with CXCR4 and CXCR7 small interfering RNA (siRNA) arrested cells in S phase. CXCL12/CXCR4 and CXCL12/CXCR7 receptor ligand systems affect the invasion of endometrial carcinoma cell line into Ishikawa and HEC-1-A. CXCR4 and CXCR7 were silenced by RNAi, which can inhibit the invasion of Ishikawa and HEC-1-A cell lines. Hence, CXCR4 and CXCR7 are expected to become two target genes for the treatment of endometrial carcinoma

  7. Mechanisms of Normal and Abnormal Endometrial Bleeding

    PubMed Central

    Lockwood, Charles J.

    2011-01-01

    Expression of tissue factor (TF), the primary initiator of coagulation, is enhanced in decidualized human endometrial stromal cells (HESC) during the progesterone-dominated luteal phase. Progesterone also augments a second HESC hemostatic factor, plasminogen activator inhibitor-1 (PAI-1). In contrast, progestins inhibit HESC matrix metalloproteinase (MMP)-1, 3 and 9 expression to stabilize endometrial stromal and vascular extracellular matrix. Through these mechanisms decidualized endometrium is rendered both hemostatic and resistant to excess trophoblast invasion in the mid-luteal phase and throughout gestation to prevent hemorrhage and accreta. In non-fertile cycles, progesterone withdrawal results in decreased HESC TF and PAI-expression and increased MMP activity and inflammatory cytokine production promoting the controlled hemorrhage of menstruation and related tissue sloughing. In contrast to these well ordered biochemical processes, unpredictable endometrial bleeding associated with anovulation reflects absence of progestational effects on TF, PAI-1 and MMP activity as well as unrestrained angiogenesis rendering the endometrium non-hemostatic, proteolytic and highly vascular. Abnormal bleeding associated with long-term progestin-only contraceptives results not from impaired hemostasis but from unrestrained angiogenesis leading to large fragile endometrial vessels. This abnormal angiogenesis reflects progestational inhibition of endometrial blood flow promoting local hypoxia and generation of reactive oxygen species that increase production of angiogenic factors such as vascular endothelial growth factor (VEGF) in HESCs and Angiopoietin-2 (Ang-2) in endometrial endothelial cells while decreasing HESC expression of angiostatic, Ang-1. The resulting vessel fragility promotes bleeding. Aberrant angiogenesis also underlies abnormal bleeding associated with myomas and endometrial polyps however there are gaps in our understanding of this pathology. PMID:21499503

  8. Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

    PubMed Central

    Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

    2015-01-01

    High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas. PMID:26448930

  9. Research and development of intelligent controller for high-grade sanitary ware

    NASA Astrophysics Data System (ADS)

    Bao, Kongjun; Shen, Qingping

    2013-03-01

    With the social and economic development and people's living standards improve, more and more emphasis on modern society, people improve the quality of family life, the use of intelligent controller applications in high-grade sanitary ware physiotherapy students. Analysis of high-grade sanitary ware physiotherapy common functions pointed out in the production and use of the possible risks, proposed implementation of the system hardware and matching, given the system software implementation process. High-grade sanitary ware physiotherapy intelligent controller not only to achieve elegant and beautiful, simple, physical therapy, water power, deodorant, multi-function, intelligent control, to meet the consumers, the high-end sanitary ware market, strong demand, Accelerate the enterprise product Upgrade and improve the competitiveness of enterprises.

  10. Genetic Analysis of Diffuse High-Grade Astrocytomas in Infancy Defines a Novel Molecular Entity.

    PubMed

    Gielen, Gerrit H; Gessi, Marco; Buttarelli, Francesca R; Baldi, Caterina; Hammes, Jennifer; zur Muehlen, Anja; Doerner, Evelyn; Denkhaus, Dorota; Warmuth-Metz, Monika; Giangaspero, Felice; Lauriola, Libero; von Bueren, André O; Kramm, Christof M; Waha, Andreas; Pietsch, Torsten

    2015-07-01

    Pediatric high-grade gliomas are considered to be different when compared to adult high-grade gliomas in their pathogenesis and biological behavior. Recently, common genetic alterations, including mutations in the H3F3A/ATRX/DAXX pathway, have been described in approximately 30% of the pediatric cases. However, only few cases of infant high-grade gliomas have been analyzed so far. We investigated the molecular features of 35 infants with diffuse high-grade astrocytomas, including 8 anaplastic astrocytomas [World Health Organization (WHO) grade III] and 27 glioblastomas (WHO grade IV) by immunohistochemistry, multiplex ligation probe-dependent amplification (MLPA), pyrosequencing of glioma-associated genes and molecular inversion probe (MIP) assay. MIP and MLPA analyses showed that chromosomal alterations are significantly less frequent in infants compared with high-grade gliomas in older children and adults. We only identified H3F3A K27M in 2 of 34 cases (5.9%), with both tumors located in the posterior fossa. PDGFRA amplifications were absent, and CDKN2A loss could be observed only in two cases. Conversely, 1q gain (22.7%) and 6q loss (18.2%) were identified in a subgroup of tumors. Loss of SNORD located on chromosome 14q32 was observed in 27.3% of the infant tumors, a focal copy number change not previously described in gliomas. Our findings indicate that infant high-grade gliomas appear to represent a distinct genetic entity suggesting a different pathogenesis and biological behavior. PMID:25231549

  11. Expression, Epigenetic and Genetic Changes of HNF1B in Endometrial Lesions.

    PubMed

    Němejcová, Kristýna; Tichá, Ivana; Kleiblová, Petra; Bártů, Michaela; Cibula, David; Jirsová, Kateřina; Dundr, Pavel

    2016-07-01

    Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group. We detected expression of HNF-1-beta in 28 % of ECs (51/180 cases), 26 % of serous carcinoma (7/27 cases), 83 % of endometrial clear cell carcinoma (15/18 cases), 93 % of hyperplastic polyps with atypias (13/14 cases), 100 % of hyperplastic polyps without atypias (16/16 cases), 88 % of hyperplasias with atypias (14/16 cases), 91 % of hyperplasias without atypias (10/11 cases), and in ≥80 % of different normal endometrium samples. The control group of OCCCs showed HNF-1-beta expression in 95 % (18/19 cases). Methylation in promoter region was detected in 13.3 % (4/30) of ECs, but not in corresponding normal tissue where available, nor in OCCCs (0/15 cases). Mutation analysis revealed truncating variant c.454C > T (p.Gln152X) in one EC and missense variant c.848C > T (p.Ala283Val) was detected in one OCCC. In conclusion, expression of HNF-1-beta was detected in various extents in all types of lesions analyzed, nevertheless its strong expression was mostly limited to clear cell carcinomas. Biological significance of genetic and epigenetic changes needs further investigation. PMID:26685938

  12. Endometrial LGR7 expression and implantation failure.

    PubMed

    Campitiello, Maria Rosaria; Caprio, Francesca; Mele, Daniela; D'eufemia, Diletta; Colacurci, Nicola; De Franciscis, Pasquale

    2016-06-01

    Implantation failure is considered as a major cause of infertility in women with recurrent pregnancy loss (RPL) and in otherwise healthy women with unexplained infertility. Preliminary data in primates suggested that relaxin (RLX) is involved in endometrial preparation for implantation. In a prospective observational study, the endometrial RLX receptor (LGR7) expression was assessed in three groups of patients with regular ovulatory cycle and normal uterine cavity: 23 with RPL (Group A), 23 with unexplained infertility undergone at least three cycles of failed in vitro fertilization (IVF) reporting good oocyte and embryo quality (Group B), 23 with proven fertility (Group C). Assessment of LGR7 expression was performed with both polymerase chain reaction (PCR) analysis and immunohistochemistry on endometrial samples obtained with hysteroscopic biopsy performed in the secretory phase of the menstrual cycle. Endometrial LGR7 was less expressed in group A and B versus C, both by PCR analysis (p = 0.024) and immunohistochemistry. The decreased expression of the endometrial RLX receptor in women with implantation failures, both in vitro fertilization failure and recurrent pregnancy loss, suggests that RLX may play a crucial role in the structural and functional changes of the endometrium during the window of implantation. PMID:26761440

  13. Hospital-Based Study of Epithelial Malignancies of Endometrial Cancer Frequency in Lahore, Pakistan, and Common Diagnostic Pitfalls

    PubMed Central

    Riaz, Sabiha; Hussain, Afshan; Mehboob, Riffat; Shams, M. Usman; Khan, Haseeb Ahmad

    2014-01-01

    The current study was conducted to see the frequency of epithelial malignancies of endometrium with focus on the common diagnostic pitfalls and identify morphological and immunohistochemical markers helpful in the differential diagnosis between different subtypes. It is a retrospective descriptive study carried out on 52 specimens of endometrial tumors received in Fatima Memorial Hospital, Lahore, Pakistan, during three years (2010–2012). Patients were divided into 5 age groups: <40, 41–50, 51–60, 61–70, and >70 yrs. Tissues were fixed in 10% formalin and processed and stained with haematoxylin-eosin. Stained slides were examined to determine the histological types by WHO classification, and immunohistochemistry for WT1, p53, ER/PR, and MIB1 was done in cases where morphology alone was not helpful in making a confirmed diagnosis. 80% of specimens were of endometrioid adenocarcinomas, 11% of serous tumors, 4% of clear cell carcinoma, and 4% of squamous cell carcinomas involving both cervix and endometrium. Most of the patients (28.84%) with endometrial carcinomas fall in the age range of 51–60 yrs. Endometrioid adenocarcinoma is the most common type of epithelial endometrial malignancies. Morphology is the keystone in the evaluation of these tumors, but immunohistochemistry can also be helpful in establishing the correct diagnosis. PMID:24523984

  14. Immunophenotype and K-RAS mutation in mucinous ovarian adenocarcinoma with mural nodule of high-grade sarcoma: case report.

    PubMed

    Desouki, Mohamed M; Fadare, Oluwole; Kanbour, Anisa; Kanbour-Shakir, Amal

    2014-03-01

    Ovarian mucinous tumors with mural nodules are rare. The mural nodules are microscopically divergent neoplasms of varying sizes that may be benign (eg, sarcoma-like and carcinosarcoma-like), or malignant (eg, anaplastic carcinoma and sarcoma). The K-RAS gene mutation in ovarian mucinous neoplasms with mural nodules has not been previously reported. This is a case report of a 25-year-old female diagnosed with ovarian invasive mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous tumor component demonstrated a K-RAS codon 12/13 mutation (p.G12V, c.35 G>T), whereas the sarcomatous component demonstrated a K-RAS codon 12/13 mutation (p.G12D, c.35 G>A). Although both tumor components revealed a mutation in codon 12 of K-RAS, they were of different nucleotide substitutions, indicating that these 2 tumor components were of different clonal origins. However, the fact that the 2 mutations identified in the tumor components are the most common mutations reported in mucinous tumors of the ovary, raises the possibility that sarcomatous mural nodules simply represent a form of dedifferentiation in mucinous tumors. PMID:24487474

  15. Management of high-grade stage I adenocarcinoma of the endometrium: hysterectomy following low dose external beam pelvic irradiation

    SciTech Connect

    Shimm, D.S.; Wang, C.C.; Fuller, A.F. Jr.; Nelson, J.H. Jr.; Nikrui, N.; Young, R.H.; Scully, R.E.

    1986-02-01

    Sixty-eight patients with FIGO stage I, grade 2 or 3 adenocarcinoma of the endometrium were treated according to a protocol involving 10 Gy external pelvic irradiation, prompt hysterectomy with surgical staging, and postoperative therapy individualized according to surgical-pathologic findings. Five-year survival for the entire group was 78%, 87% for those with grade 2 disease, and 59% for those with grade 3 disease. For patients whose disease was found to be confined to the uterus, surgical stage I, the 5-year survival was 98%. Patients with surgical stage I, grades 2 and 3 disease had 97 and 100% probabilities of surviving 5 years, respectively. Five-year disease-free probability was 96% for all patients with surgical stage I carcinoma, 97% for patients with grade 2 disease, and 94% for patients with grade 3 disease. Myometrial penetration influenced survival; no patient with less than 50% myometrial penetration died or suffered a relapse, while only 40% of patients with deeper penetration survived 5 years. Twenty-three percent of patients with surgically confirmed disease spread beyond the corpus survived 5 years; 29% remained disease-free at this interval. Ten of the 68 patients developed recurrences, none has had a known pelvic recurrence. Two major complications, one requiring surgery, were seen, both in patients receiving postoperative external beam irradiation. The rationale behind low-dose, preoperative external pelvic irradiation is described, and an approach to high-grade, FIGO stage I adenocarcinoma of the endometrium is outlined.

  16. Signalling pathways in endometrial cancer.

    PubMed

    Markowska, Anna; Pawałowska, Monika; Lubin, Jolanta; Markowska, Janina

    2014-01-01

    Carcinogenesis is a multistage process, during which the activity of signalling pathways responsible for cell cycle regulation and division is disrupted which leads to inhibition of apoptosis and enhanced proliferation. Improper activation of Wnt/β-catenin and PI3K. Akt pathways play essential role in endometrial cancers (EC), mainly type I. Mutations in APC, axin or CTNBB1 may lead to β-catenin overactivation leading to excessive gene expression. PTEN inactivation, mutations in the PIK3CA or Akt result in increased transmission in the PI3K/Akt pathway, apoptosis inhibition, intensive cell division, mTOR excitation. In non-endometrioid cancers, key mutations include suppressor gene TP53 responsible for repairing damaged DNA or apoptosis initiation. Irregularities in gene P16, encoding a protein forming the p16-cyclinD/CDK-pRb have also been described. Understanding the complex relations between specific proteins taking part in signal transduction of the abovementioned pathways is key to research on drugs used in targeted therapy. PMID:25520571

  17. Characterization of endometrial mesenchymal stem-like cells obtained by endometrial biopsy during routine diagnostics.

    PubMed

    Schüring, Andreas N; Schulte, Nicole; Kelsch, Reinhard; Röpke, Albrecht; Kiesel, Ludwig; Götte, Martin

    2011-01-01

    Endometrial cell clones derived from in vitro cultured purified stromal cells obtained by endometrial biopsy display characteristic stem cell features, including clonality; long-term culturing properties; multilineage differentiation potential; expression of CD146, CD105, CD90, CD73, MSI1, NOTCH1, and SOX2; and absence of CD34 and CD14 expression. We conclude that adult stem cells are present in endometrial biopsies performed in a routine clinical setting, offering new large-scale approaches for future research, diagnostics, and therapies involving adult stem cells. PMID:20864098

  18. Uterine endometrial polyp with severe hemorrhage and cystic endometrial hyperplasia-pyometra complex in a dog.

    PubMed

    Gumber, Sanjeev; Springer, Nora; Wakamatsu, Nobuko

    2010-05-01

    The current report describes an unusual presentation of uterine endometrial polyp with severe hemorrhage and cystic endometrial hyperplasia-pyometra complex in a 9.5-year-old female Doberman Pinscher. The dog presented with a 2-day history of bloody discharge from the vulva and an enlarged abdomen. The postmortem examination revealed a markedly distended right uterine horn with a large pedunculated mass (17 cm x 9 cm x 4 cm) and blood. Based on the histological findings, the diagnosis of uterine endometrial polyp was made. PMID:20453227

  19. Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study

    PubMed Central

    2010-01-01

    Background Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival. Methods Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400× magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis. Results The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD. Conclusion Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of

  20. Serum Amyloid A (SAA): a Novel Biomarker for Endometrial Cancer

    PubMed Central

    Cocco, Emiliano; Bellone, Stefania; El-Sahwi, Karim; Cargnelutti, Marilisa; Buza, Natalia; Tavassoli, Fattaneh A.; Schwartz, Peter E.; Rutherford, Thomas J.; Pecorelli, Sergio; Santin, Alessandro D.

    2009-01-01

    Background We investigated the expression of Serum-Amyloid-A (SAA) in endometrial endometrioid carcinoma (EEC), and evaluated its potential as a serum biomarker. Methods SAA gene and protein expression levels were evaluated in EEC and normal endometrial tissues (NEC), by real time-PCR, immunohistochemistry (IHC) and flow cytometry. SAA concentration in 194 serum samples from 50 healthy-women, 42 women with benign diseases and 102 patients including 49 grade-1, 38 grade-2 and 15 grade-3 EEC was also studied by a sensitive bead-based-immunoassay. Results SAA gene expression levels were significantly higher in EEC when compared to NEC (mean-copy-number by RT-PCR = 182 vs 1.9; P=0.001). IHC revealed diffuse cytoplasmic SAA protein staining in poorly differentiated EEC tissues. High intracellular levels of SAA were identified in primary EEC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (μg/ml) had medians of 6.0 in normal healthy females and 6.0 in patients with benign disease (P=0.92). In contrast, SAA values in the serum of EEC patients had a median of 23.7 significantly higher than those of the healthy group (P=0.001) and benign group (P=0.001). Patients harboring G3 EEC were found to have SAA concentrations significantly higher than G1/G2 patients. Conclusions SAA is not only a liver-secreted-protein but is also an EEC-cell product. SAA is expressed and actively secreted by G3-EEC and it is present in high concentration in the serum of EEC patients. SAA may represent a novel biomarker for EEC to monitor disease recurrence and response to therapy. PMID:20041483

  1. Endometrial Stromal Nodule: Report of a Case

    PubMed Central

    Fdili Alaoui, F. Z.; Chaara, H.; Bouguern, H.; Melhouf, M. A.; Fatemi, H.; Belmlih, A.; Amarti, A.

    2011-01-01

    Endometrial stromal nodule (ESN) is the least common of the endometrial stromal tumors. They are rare neoplasms which are diagnosed in most instances by light microscopy. Although such nodules are benign, hysterectomy has been considered the treatment of choice to determine the margins of the tumor required for diagnosis and to differentiate it from invasive stromal sarcoma Whose prognosis is totally different. We report a case of a 45 years old woman, with presurgical diagnosis of adnexal mass or uterine tumor. She underwent a total abdominal hysterectomy. Pathologic examination revealed an endometrial stromal nodule. Through this observation, we insist on the fact that the ESNs are rare and benign entities which must be differentiated from the other invasive malignant stromal tumors; this can change the final prognosis. PMID:21423543

  2. Endometrial stromal nodule: report of a case.

    PubMed

    Fdili Alaoui, F Z; Chaara, H; Bouguern, H; Melhouf, M A; Fatemi, H; Belmlih, A; Amarti, A

    2011-01-01

    Endometrial stromal nodule (ESN) is the least common of the endometrial stromal tumors. They are rare neoplasms which are diagnosed in most instances by light microscopy. Although such nodules are benign, hysterectomy has been considered the treatment of choice to determine the margins of the tumor required for diagnosis and to differentiate it from invasive stromal sarcoma Whose prognosis is totally different. We report a case of a 45 years old woman, with presurgical diagnosis of adnexal mass or uterine tumor. She underwent a total abdominal hysterectomy. Pathologic examination revealed an endometrial stromal nodule. Through this observation, we insist on the fact that the ESNs are rare and benign entities which must be differentiated from the other invasive malignant stromal tumors; this can change the final prognosis. PMID:21423543

  3. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

    PubMed

    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

    2015-12-29

    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

  4. Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy.

    PubMed

    Yong, William H; Butte, Pramod V; Pikul, Brian K; Jo, Javier A; Fang, Qiyin; Papaioannou, Thanassis; Black, Keith; Marcu, Laura

    2006-01-01

    Neuropathology frozen section diagnoses are difficult in part because of the small tissue samples and the paucity of adjunctive rapid intraoperative stains. This study aims to explore the use of time-resolved laser-induced fluorescence spectroscopy as a rapid adjunctive tool for the diagnosis of glioma specimens and for distinction of glioma from normal tissues intraoperatively. Ten low grade gliomas, 15 high grade gliomas without necrosis, 6 high grade gliomas with necrosis and/or radiation effect, and 14 histologically uninvolved "normal" brain specimens are spectroscopicaly analyzed and contrasted. Tissue autofluorescence was induced with a pulsed Nitrogen laser (337 nm, 1.2 ns) and the transient intensity decay profiles were recorded in the 370-500 nm spectral range with a fast digitized (0.2 ns time resolution). Spectral intensities and time-dependent parameters derived from the time-resolved spectra of each site were used for tissue characterization. A linear discriminant analysis diagnostic algorithm was used for tissue classification. Both low and high grade gliomas can be distinguished from histologically uninvolved cerebral cortex and white matter with high accuracy (above 90%). In addition, the presence or absence of treatment effect and/or necrosis can be identified in high grade gliomas. Taking advantage of tissue autofluorescence, this technique facilitates a direct and rapid investigation of surgically obtained tissue. PMID:16368511

  5. Low- to high-grade metamorphic transition in the Southern part of Karnataka Nucleus, India

    NASA Astrophysics Data System (ADS)

    Naqvi, S. M.

    The southern part of Karnataka Nucleus has a strong imprint of 2.6 Ga metamorphism. This has affected the schist belts of Karnataka Nucleus from greenschist to upper amphibolite facies. The higher grades of metamorphism are in the Holenarasipur, Nuggihalli, Krishnarajpet, Hadnur and Melkote schist belts. In the high grade transition zone, around Sargur only keels of schist belts are preserved and occur as highly dismembered, disconnected belts with the top and bottom of the stratigraphic column obliterated due to high grade metamorphism and accompanying migmatization. Absence of high-grade metamorphic minerals in the sediments of the Dharwar schist belts supports the contention that high grade metamorphism post-dated the Dharwar sedimentation and occurred around 2.6 Ga ago. Sargur type metamorphism occurred at upper crustal levels and charnockite type metamorphism occurred in lower crustal levels. The P-T conditions for the mineral assemblage in metapelites of Sargur Group indicate burial depths up to at least 15 km suggesting that they were subducted and later obducted during the development of Early Proterozoic Mobile Belt along the southern border of the Karnataka Nucleus.

  6. Low- to high-grade metamorphic transition in the Southern part of Karnataka Nucleus, India

    NASA Technical Reports Server (NTRS)

    Naqvi, S. M.

    1988-01-01

    The southern part of Karnataka Nucleus has a strong imprint of 2.6 Ga metamorphism. This has affected the schist belts of Karnataka Nucleus from greenschist to upper amphibolite facies. The higher grades of metamorphism are in the Holenarasipur, Nuggihalli, Krishnarajpet, Hadnur and Melkote schist belts. In the high grade transition zone, around Sargur only keels of schist belts are preserved and occur as highly dismembered, disconnected belts with the top and bottom of the stratigraphic column obliterated due to high grade metamorphism and accompanying migmatization. Absence of high-grade metamorphic minerals in the sediments of the Dharwar schist belts supports the contention that high grade metamorphism post-dated the Dharwar sedimentation and occurred around 2.6 Ga ago. Sargur type metamorphism occurred at upper crustal levels and charnockite type metamorphism occurred in lower crustal levels. The P-T conditions for the mineral assemblage in metapelites of Sargur Group indicate burial depths up to at least 15 km suggesting that they were subducted and later obducted during the development of Early Proterozoic Mobile Belt along the southern border of the Karnataka Nucleus.

  7. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    PubMed Central

    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

    2015-01-01

    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

  8. Deep brain stimulation and development of a high-grade glioma: incidental or causal association?

    PubMed

    Mindermann, Thomas; Mendelowitsch, Aminadav

    2016-05-01

    We report the case of a patient in whom 8.8 years following the implantation of a bilateral deep brain stimulation (DBS) into the Vim, a high-grade glioma was diagnosed in close proximity to the two electrode leads. A possible relationship between the permanent DBS and the development of the brain tumour is discussed. PMID:26993141

  9. Gene Expression Patterns Related to Vascular Invasion and Aggressive Features in Endometrial Cancer

    PubMed Central

    Mannelqvist, Monica; Stefansson, Ingunn M.; Bredholt, Geir; Hellem Bø, Trond; Øyan, Anne M.; Jonassen, Inge; Kalland, Karl-Henning; Salvesen, Helga B.; Akslen, Lars A.

    2011-01-01

    The presence of tumor cells entering vascular channels is a prognostic marker for many cancers, including endometrial carcinoma. Vascular invasion is considered to be an early step in the metastatic process and important for the progress of malignant tumors. Here, we investigated the gene expression patterns related to vascular involvement in 57 primary endometrial cancers, using DNA microarray and quantitative PCR techniques. A vascular invasion signature of 18 genes was significantly associated with patient survival and clinicopathological phenotype. Vascular involvement was also related to gene sets for epithelial-mesenchymal transition, wound response, endothelial cells, and vascular endothelial growth factor (VEGF) activity. With immunohistochemical validation, both collagen 8 and matrix metalloproteinase 3 (MMP3) were associated with vascular invasion, whereas ANGPTL4 and IL-8 were associated with patient survival. Our findings indicate that vascular involvement within primary tumors is associated with gene expression profiles related to angiogenesis and epithelial-mesenchymal transition. These data could contribute to an improved understanding of potential targets for metastatic spread and may provide clinically important information for better management of endometrial cancer. PMID:21281818

  10. Postoperative vaginal radiation in endometrial cancer using a remote afterloading technique

    SciTech Connect

    Mandell, L.; Nori, D.; Anderson, L.; Hilaris, B.

    1985-03-01

    Carcinoma of the endometrium is the most common malignancy of the female genital tract. In early stage endometrial cancer, surgery remains the primary mode of treatment while radiation therapy plays an adjuvant role. Prophylactic vaginal radiation has been shown to reduce significantly the incidence of vaginal recurrences. Between the years 1969-1976, 330 patients with FIGO Stages I and II endometrial cancer were treated according to a standard departmental policy in which 40 Gy of external radiation was given to high risk Stage I and II patients in combination with surgery and intravaginal radiation. With this regimen, the mucosal surface received a total equivalent dose of 40 Gy. These treatments were given on an outpatient basis without the need for any sedation or analgesics. The minimum follow-up was 5 years, with a median follow-up of 8.5 years. The overall pelvic and/or vaginal recurrence rate was 2.7%. The incidence of vaginal complications was 3.7%. The advantages of a remote after loading technique in delivering vaginal vault radiation in endometrial cancer are discussed.

  11. Primary Endometrial Yolk Sac Tumor With Endodermal-Intestinal Differentiation Masquerading as Metastatic Colorectal Adenocarcinoma.

    PubMed

    Damato, Stephen; Haldar, Krishnayan; McCluggage, W Glenn

    2016-07-01

    Yolk sac tumors (YSTs) with a somatic glandular pattern can be difficult to recognize histologically because they reproduce developing intestinal, hepatic, or lung tissue and can express markers such as CDX2 and TTF1. We report an unusual case of a primary endometrial YST showing florid endodermal-intestinal differentiation in a 63-yr-old woman with a history of colorectal adenocarcinoma. Histologically, the tumor exhibited a glandular and papillary architecture and showed widespread immunoreactivity for CDX2 and focal staining for CK20 and CEA, mimicking metastatic colorectal carcinoma on biopsy. The presence of subnuclear cytoplasmic clearing and positive staining for germ cell markers, however, pointed toward a diagnosis of primary endometrial YST, and this was supported by the radiologic and the subsequent pathologic finding of a primary endometrial-based lesion. YSTs in this age group usually arise in association with somatic tumors and in this case a small focus of coexistent endometrioid adenocarcinoma was identified within the uterus. Despite surgery and adjuvant chemotherapy, the patient showed disease progression with liver and lung metastases 6 mo postoperatively. PMID:26598980

  12. Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer

    SciTech Connect

    Solhjem, Matthew C. . E-mail: petersen.ivy@mayo.edu; Petersen, Ivy A.; Haddock, Michael G.

    2005-08-01

    Purpose To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. Methods and Materials Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic {+-} paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. Results With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. Conclusion Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.

  13. Clinical analysis of endometrial cancer patients with obesity, diabetes, and hypertension

    PubMed Central

    Yin, Xiang-Hua; Jia, Hong-Yan; Xue, Xiao-Rui; Yang, Shi-Zhang; Wang, Zhong-Qin

    2014-01-01

    The purpose of our study was to study the postoperation outcome and incidence of deep vein thrombosis (DVT) in endometrial cancer (EC) patients with or without hypertension, diabetes, and obesity. This analysis included 219 patients with endometrial carcinoma who were treated between 2002 and 2012 at the Department of Obstetrics and Gynecology, Yangzhou University Hospital. Patients were divided into five groups based on the comorbidities. Group 1 EC & Diabetes, Group 2 EC & Hypertension, Group 3 EC & Obesity, Group 4 EC Combined two, Group 5 no combined. Then the five groups were analyzed in postoperation outcomes and DVT incidence using one-way analysis of variance or Pearson χ2 tests. we found that there was no significant difference in pelvic lymph node metastasis (P=0.102), aortic lymph node metastasis (P=0.221), and operative time (P=0.503). But there was significant difference in blood loss (P<0.01), hospital stay (P<0.01). No significant difference (P>0.05) in treatment outcome between surgical operation, surgical operation+ radiotherapy and radiotherapy. Deep vein thrombosis and pulmonary embolism have some significantly (P<0.01) (P<0.01), respectively. Compared to patients who simply suffer from endometrial cancer, diabetes make patients easy bleeding in surgery and increase hospitalization time in corresponding. VTE is a common complication of EC surgery with comorbidities, such as diabetes and hypertension, and it’s a remarkable proportion of events occurring late after surgery. PMID:24753771

  14. Uterine development and endometrial programming.

    PubMed

    Bartol, F F; Wiley, A A; Bagnell, C A

    2006-01-01

    Structural patterning and functional programming of uterine tissues are mechanistically coupled. These processes ensure anteroposterior differentiation of uterine tissues from adjacent segments of the developing female reproductive tract (FRT) and radial patterning that establishes uterine-specific histoarchitecture and functionality. Uterine organogenesis begins prenatally and is completed postnatally. Genes required for FRT development include Pax2, Lim1 and Emx2, genes in the abdominal-B Hoxa cluster, and members of both Wnt and Hedgehog (Hh) gene families. Disruption of morphoregulatory gene expression patterns can prevent FRT development entirely or compromise uterine organogenesis specifically. Oestrogen receptor-alpha (ER) -dependent events associated with development of the neonatal porcine uterus can be altered by administration of oestrogen (E) or relaxin (RLX). Expression of the RLX receptor is detectable in porcine endometrium at birth, before onset of ER expression and uterine gland genesis. Uterotrophic effects of both E and RLX can be inhibited with the ER antagonist ICl 182,780, indicating that RLX may act via crosstalk with the ER system in neonatal tissues. Exposure of neonatal gilts to E alters temporospatial patterns of Hh, Wnt and Hoxa expression in the uterine wall. Oestrogen given for two weeks from birth produced hypoplastic adult porcine uteri that were less responsive to periattachment conceptus signals as reflected by reduced growth response and luminal fluid protein accumulation, altered endometrial gene expression, and reduced capacity for conceptus support. Data reinforce the concept that factors affecting signalling events in uterine tissues that produce changes in morphoregulatory gene expression patterns during critical organisational periods can alter the developmental trajectory of the uterus with lasting consequences. Thus, uterine tissues can be programmed epigenetically for success or failure during perinatal life. PMID

  15. Endometrial evaluation with transvaginal ultrasonography for the screening of endometrial hyperplasia or cancer in premenopausal and perimenopausal women

    PubMed Central

    Kim, Min-Jeong; Kim, Jin-Ju

    2016-01-01

    Objective The aim of our study is to determine clinical factors and sonographic findings associated with endometrial hyperplasia or cancer (EH+) in premenopausal and perimenopausal women. Methods A total of 14,340 transvaginal ultrasonography examinations of 9,888 healthy premenopausal and perimenopausal women were included in this retrospective study. One hundred sixty-two subjects underwent endometrial biopsy based on abnormal uterine bleeding (AUB), sonographic endometrial abnormalities (thickened endometrium, endometrial mass, or endometrial stripe abnormality), or both. The clinical factors and sonographic endometrial abnormalities were evaluated with regard to EH+. Results Histologically verified EH+ was found in fourteen subjects (8.6%); ten cases of endometrial hyperplasia (EH) without atypia, three cases of EH with atypia (AEH), and one case of endometrial cancer. Neither clinical factors nor AUB were associated with EH+ (P=0.32) or AEH+ (P=0.72). Of sonographic findings, endometrial stripe abnormality was significantly associated with EH+ (P=0.003) and marginally associated with AEH+ (P=0.05), but a thickened endometrium was not associated with EH+ (P=0.43). Conclusion Endometrial stripe abnormality is a significant factor to predict EH+ in healthy premenopausal and perimenopausal women with and without AUB. However, simple measurement of endometrial thickness has a limited role in this capacity. PMID:27200309

  16. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    SciTech Connect

    Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray, Joe; Huntsman, David G.

    2008-05-02

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  17. Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

    SciTech Connect

    Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray,Joe; Huntsman, David G.

    2007-07-23

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  18. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    PubMed Central

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  19. Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.

    PubMed

    Gamundi-Segura, Silvia; Serna, Jose; Oehninger, Sergio; Horcajadas, Jose A; Arbones-Mainar, Jose M

    2015-09-01

    Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness. PMID:25686566

  20. ZEB1 Expression in Endometrial Biopsy Predicts Lymph Node Metastases in Patient with Endometrial Cancer

    PubMed Central

    Feng, Gang; Wang, Xiangming; Cao, Xiaozhi; Shen, Lijuan; Zhu, Jiansheng

    2014-01-01

    Purpose. The purpose of this study was to analyze the expression of zinc-finger E-box-binding homeobox 1 (ZEB1) in endometrial biopsy and its correlation with preoperative characteristics, including lymph node metastases in patient with endometrial cancer. Methods. Using quantitative RT-PCR, ZEB1 expressions in endometrial biopsy from 452 patients were measured. The relationship between ZEB1 expression and preoperative characteristics was analyzed. Results. ZEB1 expressions were significantly associated with subtype, grade, myometrial invasion, and lymph node metastases. Lymph node metastases could be identified with a sensitivity of 57.8% at specificity of 74.1% by ZEB1 expression in endometrial biopsy. Based on combination of preoperative characteristics and ZEB1 expression, lymph node metastases could be identified with a sensitivity of 62.1% at specificity of 96.2% prior to hysterectomy. Conclusion. ZEB1 expression in endometrial biopsy could help physicians to better predict the lymph node metastasis in patients with endometrial cancer prior to hysterectomy. PMID:25544793

  1. Drug delivery system for the treatment of endometrial carcinoma

    NASA Astrophysics Data System (ADS)

    Rosiak, J. M.; Kowalski, A.; Dec, W.

    1998-06-01

    It has been elaborated a polymer system containing medroxyprogesterone acetate (MPA), which is inserted by physicians into the womb in order to release the hormone inside only. The device has a shape of thin rod of diameter of 4 mm and length of 30 mm. It contains about 350 mg of MPA trapped in poly(ethylene oxide) matrix. The walls of the rod are covered with a few layers of latex, and the final product undergoes radiation sterilization. The rate of release of MPA to the physiological solution with respect to number of latex layers has been monitored by UV spectroscopy at 240 nm. The results of experiments in vitro have been compared to those obtained in vivo.

  2. Molecular Characterization of an Endometrial Endometrioid Adenocarcinoma Metastatic to a Thyroid Hürthle Cell Adenoma Showing Cancerization of Follicles.

    PubMed

    Afrogheh, Amir H; Meserve, Emily; Sadow, Peter M; Stephen, Antonia E; Nosé, Vânia; Berlin, Suzanne; Faquin, William C

    2016-09-01

    Tumor-to-tumor metastasis is rare. Herein, we present a unique case of endometrial endometrioid adenocarcinoma metastatic to a thyroid Hürthle cell adenoma 9 years after initial diagnosis. On histologic examination of the thyroid, the malignant endometrioid glands and single cells (donor tumor) were dispersed within the Hürthle cell adenoma (recipient tumor). In several sections of the adenoma with still preserved microfollicular architecture, malignant endometrial adenocarcinoma cells were admixed within oncocytic adenomatous epithelium (so-called "cancerization of the follicles"). This unusual phenomenon, to our knowledge, is a novel finding in the thyroid gland. Immunohistochemistry, subsequently elicited clinical history, and morphologic comparison of the tumor in the thyroid to the primary endometrial tumor confirmed the origin of the donor tumor cells. Molecular analysis of both the metastatic and primary endometrial tumors demonstrated PIK3CA and PTEN mutations in both tumors, as is characteristic of well-differentiated endometrioid tumors of the endometrium. Amplification of chromosome 1q was detected in both sites; however, only the metastatic tumor showed loss of chromosomes 2, 9, and 22. The morphologic differential diagnosis of metastatic endometrioid adenocarcinoma in the thyroid includes columnar cell variant of papillary thyroid carcinoma (CCVPTC) arising in a preexisting adenoma, endocrine glandular atypia within an adenoma, and metastasis from other anatomic sites. Histomorphologic differences among these entities may be subtle; therefore, knowledge of and morphologic comparison with prior malignancies and immunohistochemistry can be helpful in rendering the correct diagnosis. PMID:26687112

  3. Integrative bioinformatic analyses of an oncogenomic profile reveal the biology of endometrial cancer and guide drug discovery

    PubMed Central

    Wong, Henry Sung-Ching; Juan, Yung-Shun; Wu, Mei-Shin; Zhang, Yan-Feng; Hsu, Yu-Wen; Chen, Huang-Hui; Liu, Wei-Min; Chang, Wei-Chiao

    2016-01-01

    A major challenge in personalized cancer medicine is to establish a systematic approach to translate huge oncogenomic datasets to clinical situations and facilitate drug discovery for cancers such as endometrial carcinoma. We performed a genome-wide somatic mutation-expression association study in a total of 219 endometrial cancer patients from TCGA database, by evaluating the correlation between ∼5,800 somatic mutations to ∼13,500 gene expression levels (in total, ∼78, 500, 000 pairs). A bioinformatics pipeline was devised to identify expression-associated single nucleotide variations (eSNVs) which are crucial for endometrial cancer progression and patient prognoses. We further prioritized 394 biologically risky mutational candidates which mapped to 275 gene loci and demonstrated that these genes collaborated with expression features were significantly enriched in targets of drugs approved for solid tumors, suggesting the plausibility of drug repurposing. Taken together, we integrated a fundamental endometrial cancer genomic profile into clinical circumstances, further shedding light for clinical implementation of genomic-based therapies and guidance for drug discovery. PMID:26716509

  4. Cellular sources of tenascin-C in canine mammary carcinomas.

    PubMed

    Yoshimura, H; Michishita, M; Ohkusu-Tsukada, K; Matsuda, Y; Ishiwata, T; Naito, Z; Takahashi, K

    2015-01-01

    Tenascin-C (Tn-C) is an extracellular matrix glycoprotein implicated in the progression of several human cancers. In canine mammary carcinomas, accumulation of Tn-C has been recognized in 3 different areas: regions of proliferating myoepithelial cells in complex carcinoma, basement membrane zone in low-grade simple carcinoma, and reactive stroma in high-grade simple carcinoma. To identify the Tn-C synthesizing cells in these areas, we utilized double-labeling immunohistochemistry, branched DNA in situ hybridization, and in situ hybridization-immunohistochemistry double-labeling techniques. In complex carcinomas, Tn-C was generated by proliferating myoepithelial cells. Tn-C in low-grade simple carcinomas was also derived from myoepithelial cells existing as a basal monolayer. However, stromal Tn-C in high-grade carcinomas was mainly synthesized by fibroblasts/myofibroblasts, similar to human breast cancer. Thus, the origin of Tn-C in canine mammary carcinomas differs between low- and high-grade malignancies. The role of myoepithelial cell-generated Tn-C is not yet understood. PMID:24565830

  5. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endometrial aspirator. 884.1060 Section 884.1060... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean section, and (3) The sampling component is covered within vagina....

  6. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endometrial aspirator. 884.1060 Section 884.1060... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean section, and (3) The sampling component is covered within vagina....

  7. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  8. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  9. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  10. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial aspirator. 884.1060 Section 884.1060... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean section, and (3) The sampling component is covered within vagina....

  11. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  12. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  13. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  14. Postmenopausal tamoxifen treatment and endometrial pathology.

    PubMed

    Cohen, I; Altaras, M M; Shapira, J; Tepper, R; Beyth, Y

    1994-12-01

    Tamoxifen is widely used as adjuvant therapy for postmenopausal breast cancer patients with positive estrogen receptors. Data on a possible association of endometrial pathologies with tamoxifen treatment have been accumulating. In this review, we examine the current literature and include our own experience with this occurrence. We recommend close supervision of these patients. PMID:7885659

  15. Endometrial study in patients with postmenopausal metrorrhagia

    PubMed Central

    de Merlo, Gaspar González; Mirasol, Esteban González; García, María Teresa Gómez; Parra, Carmen Ángel; Goy, Enrique Iglesias

    2016-01-01

    Introduction The aim of the study was to devise a strategy to diagnose malign endometrial pathologies (adenocarcinoma or atypical hyperplasia) that minimizes the number of invasive tests done (hysteroscopy, aspiration biopsy or curettage) with no loss of its detection efficiency. Material and methods We retrospectively studied the clinical histories of 779 postmenopausal women at the University Hospital Complex of Albacete, for whom an endometrial study had been done (hysteroscopy, aspiration biopsy or curettage) with a 1-year follow-up between 1 March 2006 and 31 March 2008. Results There were 77 cases of a malignant pathology (66 adenocarcinomas and 11 hyperplasias with atypia); 96.1% had metrorrhagia, and there were only 3 cases of asymptomatic patients (all 3 presented endometrial thickness of > 5 mm: 10, 12 and 15 mm). The sensitivity and specificity of the transvaginal ultrasound, with a 5 mm cut-off point to diagnose a malignant pathology, were 98.4% and 30.1%, respectively; 89.1% and 99.6%, respectively, for aspiration biopsy; 83.9% and 99.1%, respectively, for hysteroscopy without biopsy; and both were 100% for biopsy. Statistical significance was considered at p < 0.05 and confidence intervals were calculated at 95%. Conclusions In postmenopausal women with metrorrhagia, the first action to take is to do a transvaginal ultrasound, followed by en endometrial study, but only if the endometrium is irregular or endometrial thickness is ≥ 5 mm; in asymptomatic women, the cut-off point should be set at 10 mm. The immediate method of choice is an ambulatory biopsy. PMID:27279854

  16. Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy

    ClinicalTrials.gov

    2014-05-05

    Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  17. Normal tissue tolerance for high-grade gliomas: is it an issue?

    PubMed

    Morris, David E; Kimple, Randall J

    2009-07-01

    In this article, we address the currently accepted dose tolerance parameters for the treatment of high-grade gliomas. The issue of normal tissue tolerance is becoming increasingly important because of the long-term survival of a significant subset of young, good performance status patients and the use of hypofractionated regimens for elderly patients with poor performance status. In addition, we address relevant clinical endpoints including clinical, pathologic, and radiographic changes and highlight the difficulty in discriminating between tumor-related and treatment-related effects. Finally, we review relevant clinical trials addressing issues of dose and/or volume parameters. Future trials for patients with high-grade gliomas should consider the inclusion of a prospective evaluation of neurocognitive function and imaging correlates of the brain to assist in the prediction, prevention, and treatment of radiation-induced damage of normal brain tissue. PMID:19464634

  18. Diagnosis of High-Grade Osteosarcoma by Radiology and Cytology: A Retrospective Study of 52 Cases

    PubMed Central

    Skoog, Lambert; Unni, Krishnan K.; Bertoni, Franco; Brosjö, Otte; Kreicbergs, Andris

    2004-01-01

    The diagnostic value of combined radiology and fine needle aspiration cytology (FNAC) was retrospectively assessed in a consecutive series of 52 patients with high-grade osteosarcoma. The series was divided into typical and atypical osteosarcomas according to radiological features and site. Thirty-two of 33 radiologically typical osteosarcoma cases were correctly diagnosed by cytology; one lesion was diagnosed as sarcoma NOS. Nineteen osteosarcoma cases were radiographically atypical. Six of these were diagnosed as osteosarcoma and another six as sarcoma NOS. In three cases another type of sarcoma was suggested. One case was falsely classified as benign. FNAC of three cases were non-diagnostic. Overall, the diagnostic difficulties pertained to the radiologically atypical cases. Notably, four of these also posed considerable difficulties in the histopathological assessment prompting external consultation. Our study suggests that open biopsy can be obviated in high-grade osteosarcomas exhibiting typical radiological features, i.e., in two-thirds. PMID:18521391

  19. Rare earth element patterns in Archean high-grade metasediments and their tectonic significance

    NASA Technical Reports Server (NTRS)

    Taylor, Stuart Ross; Rudnick, Roberta L.; Mclennan, Scott M.; Eriksson, Kenneth A.

    1986-01-01

    REE data on metasedimentary rocks from two different types of high-grade Archean terrains are presented and analyzed. The value of REEs as indicators of crustal evolution is explained; the three geologic settings (in North America, Southern Africa, and Australia) from which the samples were obtained are described; and the data are presented in extensive tables and graphs and discussed in terms of metamorphic effects, the role of accessory phases, provenance, and tectonic implications (recycling, the previous extent of high-grade terrains, and a model of Archean crustal growth). The diversity of REE patterns in shallow-shelf metasediments is attributed to local provenance, while the Eu-depleted post-Archean patterns are associated with K-rich plutons from small, stable early Archean terrains.

  20. High-grade astrocytoma (Glioblastoma Multiforme) in an Atlantic spotted dolphin (Stenella frontalis).

    PubMed

    Díaz-Delgado, J; Sacchini, S; Suárez-Bonnet, A; Sierra, E; Arbelo, M; Espinosa, A; Rodríguez-Grau Bassas, E; Mompeo, B; Pérez, L; Fernández, A

    2015-01-01

    This report describes the gross, microscopical and immunohistochemical features of a high-grade astrocytoma (glioblastoma multiforme) in an adult male Atlantic spotted dolphin (Stenella frontalis). On necropsy examination, a 5 × 2.5 × 2 cm, poorly demarcated, red, friable and locally expansile mass effaced the thalamus and the left periventricular region and extended to the left lateral ventricle of the brain. Microscopically, the mass consisted of haphazardly arranged bundles and rows of interweaving polygonal to spindle-shaped cells. These often palisaded along serpentine foci of necrosis and were surrounded by prominent vessels. Immunohistochemically, the neoplastic cells expressed glial fibrillary acidic protein, but not vimentin, S100 protein, neuron-specific enolase or neurofilament protein. A diagnosis of high-grade astrocytoma was made and this represents the first description of a glioma in a cetacean species. PMID:25728810

  1. Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer.

    PubMed

    McPherson, Andrew; Roth, Andrew; Laks, Emma; Masud, Tehmina; Bashashati, Ali; Zhang, Allen W; Ha, Gavin; Biele, Justina; Yap, Damian; Wan, Adrian; Prentice, Leah M; Khattra, Jaswinder; Smith, Maia A; Nielsen, Cydney B; Mullaly, Sarah C; Kalloger, Steve; Karnezis, Anthony; Shumansky, Karey; Siu, Celia; Rosner, Jamie; Chan, Hector Li; Ho, Julie; Melnyk, Nataliya; Senz, Janine; Yang, Winnie; Moore, Richard; Mungall, Andrew J; Marra, Marco A; Bouchard-Côté, Alexandre; Gilks, C Blake; Huntsman, David G; McAlpine, Jessica N; Aparicio, Samuel; Shah, Sohrab P

    2016-07-01

    We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers. PMID:27182968

  2. Malignant transformation of a high-grade osteoblastoma of the petrous apex with subcutaneous metastasis.

    PubMed

    Kraft, Casey T; Morrison, Robert J; Arts, H Alexander

    2016-06-01

    We describe the clinical presentation, management, and pathologic findings in a case of osteosarcoma of the petrous apex with an atypical metastasis to the lower abdominal wall. We retrospectively reviewed the record of a 49-year-old man who was diagnosed with a right petrous apex lesion, which biopsy identified as a high-grade osteoblastoma. After two attempts at en bloc resection were not curative, radiation and chemotherapy were recommended. The patient subsequently developed a cutaneous lower abdominal mass that was diagnosed as an osteosarcoma. Meanwhile, the petrous apex tumor continued to grow despite treatment until the patient died from the burden of disease. Temporal bone osteoblastomas and osteosarcomas are both extremely rare, and they can be difficult to differentiate histologically. Our case illustrates this difficulty and demonstrates the possibility of a high-grade osteoblastoma's malignant conversion to an osteosarcoma. PMID:27304442

  3. SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas.

    PubMed

    Karanian-Philippe, Marie; Velasco, Valérie; Longy, Michel; Floquet, Anne; Arnould, Laurent; Coindre, Jean-Michel; Le Naoures-Méar, Cécile; Averous, Gerlinde; Guyon, Frédéric; MacGrogan, Gaëtan; Croce, Sabrina

    2015-09-01

    Ovarian small cell carcinoma of the hypercalcemic type (SCCOHT)/ovarian rhabdoid tumor is a rare and highly malignant tumor that typically occurs in young women. Up until now the diagnosis has been made on the basis of morphology without any specific immunohistochemical (IHC) markers. However, several authors have shown recently that SCCOHTs are characterized by inactivation of the SMARCA4 gene (encoding the BRG1 protein) resulting in a loss of BRG1 protein expression in IHC. We evaluated BRG1 and INI1 expression in 12 SCCOHTs and in a series of 122 tumors that could mimic SCCOHT morphologically: 9 juvenile granulosa cell tumors, 47 adult granulosa cell tumors, 33 high-grade ovarian serous carcinomas, 9 desmoplastic round cell tumors, 13 Ewing sarcomas (5 from the pelvis and 8 from soft tissues), 1 round cell sarcoma associated with CIC-DUX4 translocation from soft tissue (thigh), 1 case of high-grade endometrial stromal sarcoma of the ovary, and 9 melanomas. Forty-four adult granulosa cell tumors were interpretable by IHC. All 12 SCCOHTs were devoid of BRG1 expression and expressed INI1. All other interpretable 119 tumors showed BRG1 nuclear positivity, with variable staining proportions, ranging from 10% to 100% of positive cells (mean: 77%, median: 80%), variable intensities (weak: 5%, moderate: 37%, strong: 58%), and distributions: diffuse in 82 cases (70%) and heterogenous in 36 cases (30%). BRG1 positivity was heterogenous in desmoplastic round cell tumors and adult granulosa cell tumors. Overall, BRG1 is a useful diagnostic marker in SCCOHT, showing the absence of expression in SCCOHT. Nevertheless, the possible heterogeneity and the variable intensity of this staining warrant caution in the interpretation of BRG1 staining in biopsy specimens. PMID:26135561

  4. Specific localization of thallium 201 in human high-grade astrocytoma by microautoradiography

    SciTech Connect

    Mountz, J.M.; Raymond, P.A.; McKeever, P.E.; Modell, J.G.; Hood, T.W.; Barthel, L.K.; Stafford-Schuck, K.A. )

    1989-07-15

    The ability to accurately distinguish remaining or recurrent high-grade astrocytoma from necrosis or edema following treatment is essential to optimal patient management. Thallium 201 planar gamma-camera imaging has been shown to be helpful in detecting recurrent high-grade astrocytoma; however, due to tissue heterogeneity adjacent to and within tumor, the cellular specificity and quantification of 201Tl uptake are largely unknown. In order to determine which tissues are responsible for the radioisotope uptake, microautoradiographic techniques were used to examine multiple tissue sections from five patients with high-grade astrocytoma. Each patient received 5 mCi of 201Tl i.v. 1 h prior to tumor removal. Additionally, all patients received computerized tomographic and 201Tl planar gamma-camera scans prior to surgery. Following surgery, the excised tissue specimens were tentatively classified by gross pathological examination and then immediately processed for dry mount autoradiography; grain density was determined over regions containing tumor, adjacent and uninvolved brain tissue, necrotic tissue, and background. Highly significant differences were found in grain densities (201Tl uptake) between tumor and uninvolved brain tissue, as well as between uninvolved brain tissue and necrotic tissue; there was no significant difference between background grain density and that in necrotic tissue. Mean grain densities (grains/cm2 +/- 1 SD) across patients were: tumor, 102 +/- 23; adjacent, uninvolved brain tissue, 29 +/- 11; necrotic tissue, 6.2 +/- 1.1; and background, 7.0 +/- 4.1. We conclude that the ability of 201Tl to selectively image high-grade astrocytoma is due to its preferential uptake into tumor cells.

  5. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer.

    PubMed

    Bowtell, David D; Böhm, Steffen; Ahmed, Ahmed A; Aspuria, Paul-Joseph; Bast, Robert C; Beral, Valerie; Berek, Jonathan S; Birrer, Michael J; Blagden, Sarah; Bookman, Michael A; Brenton, James D; Chiappinelli, Katherine B; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G; Iwanicki, Marcin; Karlan, Beth Y; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A; Lu, Karen H; McNeish, Iain A; Menon, Usha; Narod, Steven A; Nelson, Brad H; Nephew, Kenneth P; Pharoah, Paul; Powell, Daniel J; Ramos, Pilar; Romero, Iris L; Scott, Clare L; Sood, Anil K; Stronach, Euan A; Balkwill, Frances R

    2015-11-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  6. Total enbloc spondylectomy for metastatic high grade spinal tumors: Early results

    PubMed Central

    Patil, Sanganagouda S; Nene, Abhay M

    2016-01-01

    Background: High grade metastatic spinal tumors are most common and are invasive. These patients can succumb to disease progression if not treated timely. Although considered as invasive and morbid, total enbloc spondylectomy (TES) in selected cases has better survival rates. The authors describe the results of TES for high grade metastatic spinal tumors. Materials and Methods: Five patients (four females and one male) underwent TES for solitary metastatic vertebral lesion between November 2012 and January 2014. These patients presented to us with spinal instability, unrelenting severe spinal pain and/or with severe progressive radiculopathy. Average age was 46.2 years (range 39–62 years). After complete investigations, computed tomography scan, magnetic resonance imaging scan and positron emission tomography (PET) scan, it was confirmed that these patients had high grade solitary vertebral metastatic tumor. Results: Average duration of followup was 18 months (range 16–20 months). The average preoperative visual analog scale score of 9.4 (range 9–10) improved to 2 (range 1–4) at last followup. Average blood loss was 1440 mL (range 1000–2000 mL). Average duration of surgery was 198 min (range 180–240 min). Significant pain relief was noticed in each patient in the immediate postoperative period and during followups. These patients attained complete functional activities of daily living with in a month. The imaging showed implants in situ, no recurrence of tumor, and no activity on PET scan at the final followup. Conclusion: The present series shows favorable short term results of TES for solitary, metastatic, high grade vertebral body tumors by a team approach. PMID:27512215

  7. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

    PubMed Central

    Bowtell, David D.; Böhm, Steffen; Ahmed, Ahmed A.; Aspuria, Paul-Joseph; Bast, Robert C.; Beral, Valerie; Berek, Jonathan S.; Birrer, Michael J.; Blagden, Sarah; Bookman, Michael A.; Brenton, James; Chiappinelli, Katherine B.; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G.; Iwanicki, Marcin; Karlan, Beth Y.; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A.; Lu, Karen H.; McNeish, Iain A.; Menon, Usha; Narod, Steve A.; Nelson, Brad H.; Nephew, Kenneth P.; Pharoah, Paul; Powell, Daniel J.; Ramos, Pilar; Romero, Iris L.; Scott, Clare L.; Sood, Anil K.; Stronach, Euan A.; Balkwill, Frances R.

    2016-01-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This ‘roadmap’ for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  8. Toppling high-grade pulmonary neuroendocrine tumors with a DLL3-targeted trojan horse.

    PubMed

    Dylla, Scott J

    2016-03-01

    Delta-like protein 3 (DLL3) is a novel and tractable tumor-initiating cell-associated target for the antibody-drug conjugate SC16LD6.5 in high-grade pulmonary neuroendocrine tumors. Elevated expression of DLL3, an inhibitor of Notch pathway activation, marks the second recent observation that impairment of Notch receptor signaling may play a critical role in neuroendocrine tumorigenesis. PMID:27308627

  9. Feasibility of Using Bevacizumab With Radiation Therapy and Temozolomide in Newly Diagnosed High-Grade Glioma

    SciTech Connect

    Narayana, Ashwatha Golfinos, John G.; Fischer, Ingeborg; Raza, Shahzad; Kelly, Patrick M.D.; Parker, Erik; Knopp, Edmond A.; Medabalmi, Praveen; Zagzag, David; Eagan, Patricia; Gruber, Michael L.

    2008-10-01

    Introduction: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. Methods and Materials: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m{sup 2}. Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m{sup 2} for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. Results: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. Conclusion: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.

  10. Clonal evolution of B cells in transformation from low- to high-grade lymphoma

    PubMed Central

    Matolcsy, András; Schattner, Elaine J.; Knowles, Daniel M.; Casali, Paolo

    2015-01-01

    An outcome of low-grade B cell non-Hodgkins's lymphomas is the transformation to high-grade diffuse large B cell lymphomas (DLBL). To investigate the mechanisms of clonal evolution in the transformation to DLBL, we performed longitudinal molecular analyses of immunoglobulin (Ig), VHDJH gene sequences expressed in cases of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL) that transformed to DLBL. Among the neoplastic CLL and SLL cells and their respective high-grade transformants, there was no evidence for a clonotypic shift or acquired mutations in the expressed Ig VHDJH gene segments, as further confirmed by a specific and sensitive PCR-single strand polymorphism analysis. In contrast, among the FL cells there was a high degree of intraclonal diversification with highly divergent VHDJH gene sequences. Despite this intraclonal heterogeneity, the related DLBL expressed a collinear but unique VHDJH gene sequence. The intraclonal genealogical tree for the FL case demonstrated that the DLBL emerged in association with unique VHDJH gene mutational events. Among the intraclonal FL and related DLBL transformants, the nature and distribution of the Ig VHDJH gene mutations were consistent with antigenic selection. Thus, clonal evolution in the transformation from low- to high-grade B cell lymphoma may involve distinct pathways which vary according to the cellular origin and the type of the progenitor B cell tumor. PMID:10229093

  11. ERK1 as a Therapeutic Target for Dendritic Cell Vaccination against High-Grade Gliomas.

    PubMed

    Ku, Min-Chi; Edes, Inan; Bendix, Ivo; Pohlmann, Andreas; Waiczies, Helmar; Prozorovski, Tim; Günther, Martin; Martin, Conrad; Pagès, Gilles; Wolf, Susanne A; Kettenmann, Helmut; Uckert, Wolfgang; Niendorf, Thoralf; Waiczies, Sonia

    2016-08-01

    Glioma regression requires the recruitment of potent antitumor immune cells into the tumor microenvironment. Dendritic cells (DC) play a role in immune responses to these tumors. The fact that DC vaccines do not effectively combat high-grade gliomas, however, suggests that DCs need to be genetically modified specifically to promote their migration to tumor relevant sites. Previously, we identified extracellular signal-regulated kinase (ERK1) as a regulator of DC immunogenicity and brain autoimmunity. In the current study, we made use of modern magnetic resonance methods to study the role of ERK1 in regulating DC migration and tumor progression in a model of high-grade glioma. We found that ERK1-deficient mice are more resistant to the development of gliomas, and tumor growth in these mice is accompanied by a higher infiltration of leukocytes. ERK1-deficient DCs exhibit an increase in migration that is associated with sustained Cdc42 activation and increased expression of actin-associated cytoskeleton-organizing proteins. We also demonstrated that ERK1 deletion potentiates DC vaccination and provides a survival advantage in high-grade gliomas. Considering the therapeutic significance of these results, we propose ERK1-deleted DC vaccines as an additional means of eradicating resilient tumor cells and preventing tumor recurrence. Mol Cancer Ther; 15(8); 1975-87. ©2016 AACR. PMID:27256374

  12. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    PubMed

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome. PMID:25175810

  13. An update of the classical Bokhman's dualistic model of endometrial cancer.

    PubMed

    Wilczyński, Miłosz; Danielska, Justyna; Wilczyński, Jacek

    2016-06-01

    According to the classical dualistic model introduced by Bokhman in 1983, endometrial cancer (EC) is divided into two basic types. The prototypical histological type for type I and type II of EC is endometrioid carcinoma and serous carcinoma, respectively. The traditional classification is based on clinical, endocrine and histopathological features, however, it sometimes does not reflect the full heterogeneity of EC. New molecular evidence, supported by clinical diversity of the cancer, indicates that the classical dualistic model is valid only to some extent. The review updates a mutational diversity of EC, introducing a new molecular classification of the tumour in regard to data presented by The Cancer Genome Atlas Research Network (TGCA). PMID:27582678

  14. CD82 expression alters with human endometrial cycles and affects the uterine endometrial receptivity in vitro.

    PubMed

    Wei, Xiaowei; Liu, Shuai; Wang, Xiaoqi; Yan, Qiu

    2012-03-01

    Embryo implantation is a process that requires both temporal and spatial synchronization of the uterine endometrium and the embryo, and the endometrium becomes receptive to the embryo during the window of implantation. Although the expression patterns of many implantation-related molecules change dynamically during this process, the impact of CD82 on endometrial receptivity has not been elucidated. By immunohistochemical staining, we found that CD82 levels rose from the proliferative phase to the secretory phase in human endometrium. Specifically, the highest level appeared in mid- and late-secretory phases. Consistently, RL95-2 cells, representative of high-receptive endometrial epithelium, expressed higher levels of CD82 than did HEC-1A cells, which are representative of low-receptive endometrial epithelium, as detected by reverse transcription-polymerase chain reaction, Western blot and immunofluorescence. Furthermore, progesterone up-regulated the expression of CD82 in both epithelial cell lines. Down-regulation of CD82 in RL95-2 cells by either CD82 siRNA transfection or treatment with a CD82 antibody significantly decreased the adhesion of human embryonic JAR cells to RL95-2 cell monolayers (P < 0.01) and inhibited the phosphorylation of focal adhesion kinase (FAK). In contrast, up-regulation of CD82 in HEC-1A cells by CD82 cDNA transfection promoted embryonic JAR cell adhesion to HEC-1A monolayers (P < 0.05) and activated the phosphorylation of FAK. In conclusion, the expression of CD82 increases in endometrial tissues during the window of embryo implantation, CD82 expression affects endometrial receptivity of the uterine epithelial cells in vitro, and the FAK signaling pathway may be involved in this phenomenon. The correlation between CD82 and endometrial receptivity suggests that CD82 may serve as a potential marker of endometrial function. PMID:22393164

  15. Endometrial intraepithelial neoplasia terminology in practice: 4-year experience at a single institution.

    PubMed

    Kane, Sarah E; Hecht, Jonathan L

    2012-03-01

    An alternative WHO classification system for endometrial precancers and hyperplasia separates a lesion called endometrial intraepithelial neoplasia (EIN) from diffuse hormonal effects and cancer, resulting in a 3-category system. EIN is a localized lesion with objective histologic criteria, characterized by monoclonal growth of mutated cells, and associated with a 45-fold elevated cancer risk. This study summarizes our department's experience with EIN diagnoses in the 4 years since conversion to the new terminology. We identified all reports from endometrial samples diagnosed as EIN or including the terms "gland crowding" or "atypia" since conversion and obtained follow-up information from subsequent pathology specimens or clinic notes (82%). The diagnoses were reported by a mixture of pathologists, the majority of whom are not subspecialized to gynecologic pathology and the slides were not reviewed. Overall, 17.1% of women with EIN had carcinoma and 34.9% had either carcinoma or persistent EIN. The proportion of women with EIN or cancer on follow-up did not trend with years since adoption of EIN terminology. The median age at the time of diagnosis was 55 years in an overall population of women who underwent sampling at a median age of 47 years. The median follow-up time was 4 months. All cancers were of endometrioid histology; all but 2 were International Federation of Gynecology and Obstetrics grade 1. In comparison with a previous reproducibility study among expert pathologists on a comparable population from our department, these results for general pathologists show a higher false positive rate for subsequent cancer. PMID:22317874

  16. Aberrant Regulation of the BST2 (Tetherin) Promoter Enhances Cell Proliferation and Apoptosis Evasion in High Grade Breast Cancer Cells

    PubMed Central

    Sayeed, Aejaz; Luciani-Torres, Gloria; Meng, Zhenhang; Bennington, James L.; Moore, Dan H.; Dairkee, Shanaz H.

    2013-01-01

    Normal cellular phenotypes that serve an oncogenic function during tumorigenesis are potential candidates for cancer targeting drugs. Within a subset of invasive primary breast carcinoma, we observed relatively abundant expression of Tetherin, a cell surface protein encoded by the Bone Marrow Stromal Cell Antigen (BST2) known to play an inhibitory role in viral release from infected immune cells of the host. Using breast cancer cell lines derived from low and intermediate histopathologic grade invasive primary tumors that maintain growth-suppressive TGFβ signaling, we demonstrate that BST2 is negatively regulated by the TGFβ axis in epithelial cells. Binding of the transcription factor AP2 to the BST2 promoter was attenuated by inhibition of the TGFβ pathway thereby increasing BST2 expression in tumor cells. In contrast, inherent TGFβ resistance characteristic of high grade breast tumors is a key factor underlying compromised BST2 regulation, and consequently its constitutive overexpression relative to non-malignant breast epithelium, and to most low and intermediate grade cancer cells. In both 2-dimensional and 3-dimensional growth conditions, BST2-silenced tumor cells displayed an enhancement in tamoxifen or staurosporine-induced apoptotic cell death together with a reduction in the S-phase fraction compared to BST2 overexpressing counterparts. In a subset of breast cancer patients treated with pro apoptotic hormonal therapy, BST2 expression correlated with a trend for poor clinical outcome, further supporting its role in conferring an anti apoptotic phenotype. Similar to the effects of gene manipulation, declining levels of endogenous BST2 induced by the phytoalexin – resveratrol, restored apoptotic function, and curbed cell proliferation. We provide evidence for a direct approach that diminishes aberrant BST2 expression in cancer cells as an early targeting strategy to assist in surmounting resistance to pro apoptotic therapies. PMID:23840623

  17. Preoperative Patient Reported Mental Health is Associated with High Grade Complications after Radical Cystectomy

    PubMed Central

    Sharma, Pranav; Henriksen, Carl H.; Zargar-Shoshtari, Kamran; Xin, Ren; Poch, Michael A.; Pow-Sang, Julio M.; Sexton, Wade J.; Spiess, Philippe E.; Gilbert, Scott M.

    2016-01-01

    Purpose Psychological distress has been associated with an impaired immune response and poor wound healing. We hypothesized that preoperative patient reported mental health would be associated with high grade 30-day complications after radical cystectomy. Materials and Methods We retrospectively identified patients who underwent radical cystectomy for bladder cancer who completed Short Form 12 (SF-12) surveys for self-assessment of health status less than 6 months before surgery. Median physical and mental composite scores were calculated. An expert model including known predictors of postoperative high grade complications was developed, and SF-12 physical composite score and mental composite score were added to determine their association with this end point. Results From January 2010 to August 2014, 472 patients underwent radical cystectomy for bladder cancer, of whom 274 (58.1%) completed preoperative SF-12 questionnaires. Responders were more likely to be white (p=0.024), have higher preoperative albumin (p=0.037), receive neoadjuvant chemotherapy (p=0.002), have pT3/T4 disease (p=0.044) and have positive soft tissue surgical margins (p=0.006). Median SF-12 physical composite score was 43.1 (IQR 33.0–51.5) and mental composite score was 48.5 (IQR 39.5–54.7) in responders. Overall 46 (16.8%) responders experienced a high grade 30-day complication. Patients with a high grade complication had a lower preoperative median SF-12 mental composite score (44.8 vs 49.8, p=0.004) but no difference in physical composite score (39.2 vs 43.8, p=0.06). SF-12 mental composite score was also a significant predictive variable when added to our expert model (p=0.01). Conclusions Preoperative patient reported mental health was independently associated with high grade complications after radical cystectomy. Therefore, patient self-assessment of health status before surgery through validated questionnaires may provide additional information useful in predicting short

  18. Endometrial adenocarcinoma in a 13-year-old girl

    PubMed Central

    Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young

    2016-01-01

    Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature. PMID:27004208

  19. Endometrial adenocarcinoma in a 13-year-old girl.

    PubMed

    Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young; Rhee, Jeong Ho

    2016-03-01

    Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature. PMID:27004208

  20. Detection of endometrial lesions by degree of linear polarization maps

    NASA Astrophysics Data System (ADS)

    Kim, Jihoon; Fazleabas, Asgerally; Walsh, Joseph T.

    2010-02-01

    Endometriosis is one of the most common causes of chronic pelvic pain and infertility and is characterized by the presence of endometrial glands and stroma outside of the uterine cavity. A novel laparoscopic polarization imaging system was designed to detect endometriosis by imaging endometrial lesions. Linearly polarized light with varying incident polarization angles illuminated endometrial lesions. Degree of linear polarization image maps of endometrial lesions were constructed by using remitted polarized light. The image maps were compared with regular laparoscopy image. The degree of linear polarization map contributed to the detection of endometriosis by revealing structures inside the lesion. The utilization of rotating incident polarization angle (IPA) for the linearly polarized light provides extended understanding of endometrial lesions. The developed polarization system with varying IPA and the collected image maps could provide improved characterization of endometrial lesions via higher visibility of the structure of the lesions and thereby improve diagnosis of endometriosis.

  1. Composite encapsulated papillary carcinoma and solid papillary carcinoma.

    PubMed

    Cui, Xiaoyan; Wei, Shi

    2015-03-01

    Encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC) are distinctive variants of intraductal papillary carcinomas, each accounting for <1% of breast carcinomas. Here we report a composite carcinoma consisting of EPC and SPC. A 73-year-old woman was found to have a high density mass in the left breast on mammogram. A biopsy showed intermediate to high grade ductal carcinoma in situ (DCIS). Gross examination of the lumpectomy specimen revealed a solid, multinodular mass. Microscopic examination demonstrated two morphologically distinct intraductal carcinomas intermingled with each other. One had delicate papillae in multi-cystic spaces surrounded by thick fibrous capsule, consistent with EPC. The other had solid tumor nests with delicate fibrovascular cores. The cells were monotonous with round nuclei and salt and pepper-like chromatin, characteristic of SPC. The lack of myoepithelial cells within the papillae and at the periphery of the lesion was confirmed by immunostaining for p63 and CK5/6. Neuroendocrine differentiation of SPC was demonstrated by neuron specific enolase staining. To our knowledge, this is the first reported case of composite EPC and SPC. It raises an interesting question as to a possible common pathway of carcinogenesis of these two rare variants. PMID:25545718

  2. 5α-reductase Inhibitors and Risk of High-grade or Lethal Prostate Cancer

    PubMed Central

    Preston, Mark A.; Wilson, Kathryn; Markt, Sarah C.; Ge, Rongbin; Morash, Christopher; Stampfer, Meir J.; Loda, Massimo F.; Giovannucci, Edward; Mucci, Lorelei A.; Olumi, Aria F.

    2014-01-01

    Importance 5α-reductase inhibitors (5ARIs) are widely used for benign prostatic hyperplasia despite controversy regarding potential risk of high-grade prostate cancer with use. Furthermore, the effect of 5ARIs on progression and prostate cancer death remains unclear. Objective To determine the association between 5ARI use and development of high-grade or lethal prostate cancer. Design, Setting, and Participants Prospective observational study of 38,058 men followed for prostate cancer diagnosis and outcomes between 1996–2010 in the Health Professionals Follow-up Study. Exposure Use of 5ARIs between 1996–2010. Main Outcome Measures Cox proportional hazards models were used to estimate risk of prostate cancer diagnosis or development of lethal disease with 5ARI use, adjusting for possible confounders including prostate specific antigen testing. Results During 448,803 person-years of follow-up, we ascertained 3681 incident prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were high-grade (Gleason 8–10), 1238 were Gleason grade 7, and 1600 were low-grade (Gleason 2–6). A total of 2878 (7.6%) men reported use of 5ARIs between 1996 and 2010. After adjusting for confounders, men who reported ever using 5ARIs over the study period had a reduced risk of overall prostate cancer (HR 0.77; 95% CI, 0.65–0.91). 5ARI users had a reduced risk of Gleason 7 (HR 0.67; 95% CI, 0.49–0.91) and low-grade (Gleason 2–6) prostate cancer (HR 0.74; 95% CI, 0.57–0.95). 5ARI use was not associated with risk of high-grade (Gleason 8–10, HR 0.97; 95% CI, 0.64–1.46) or lethal disease (HR 0.99; 95% CI, 0.58–1.69). Increased duration of use was associated with significantly lower risk of overall prostate cancer (HR for 1 year of additional use 0.95; 95% CI, 0.92–0.99), localized (HR 0.95; 95% CI, 0.90–1.00), and low-grade disease (HR 0.92; 95% CI, 0.85–0.99). There was no association for lethal, high-grade, or grade 7 disease. Conclusions and

  3. Factors affecting intrauterine contraceptive device performance. I. Endometrial cavity length.

    PubMed

    Hasson, H M; Berger, G S; Edelman, D A

    1976-12-15

    The relationship of endometrial cavity length to intrauterine contraceptive device (IUD) performance was evaluated in 319 patients wearing three types of devices. The rate of events, defined as pregnancy, expulsion, or medical removal, increased significantly when the length of the IUD was equal to, exceeded, or was shorter by two or more centimeters than the length of the endometrial cavity. Total uterine length was found to be a less accurate prognostic indicator of IUD performance than endometrial cavity length alone. PMID:998687

  4. A strategy for the control of endometrial cancer.

    PubMed Central

    Gusberg, S. B.

    1975-01-01

    Epidemiologic studies can provide us with etiological clues and help us recognize high risk factors. The definition of high risk factors, especially in the perimenopausal years can lead to prophylactic measures that may aid in the control of endometrial cancer. Recognition of the high risk patient in the perimenopausal years by aspiration curettage of ambulatory women may offer a significant strategy of surveillance. The advent of modern steroid metabolic technology promises to help us clarify the problems of hormone sensitivity of this tumor so that we may properly translate these data into therapeutic action. Virulence scales can help the choice of treatment for invasive carcinoma so that patients with tumors of low virulence do not suffer from an excess of complications nor those with tumors of high virulence an excess of failure to control. In this manner we can define the role of radiotherapy and surgery, elect combined treatment when indicated and select radical surgery as indicated. There is evidence to suggest that the developmental concept of this tumor may lead to its control in a manner similar to that occurring with cervix cancer. PMID:1166055

  5. Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer

    PubMed Central

    UMENE, KIYOKO; YANOKURA, MEGUMI; BANNO, KOUJI; IRIE, HARUKO; ADACHI, MASATAKA; IIDA, MIHO; NAKAMURA, KANAKO; NOGAMI, YUYA; MASUDA, KENTA; KOBAYASHI, YUSUKE; TOMINAGA, EIICHIRO; AOKI, DAISUKE

    2015-01-01

    Aurora kinase A (AURKA) regulates the cell cycle checkpoint and maintains genomic integrity. AURKA is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. To investigate the role of AURKA in endometrial cancer, we evaluated the association of immunohistochemical expression of AURKA with clinicopathological factors. Furthermore, we examined the effects of AURKA inhibition by transfected siRNA in HEC-1B cells on colony-forming ability, invasion and migration capacity, and chemosensitivity. Immunohistochemical staining showed that overexpression of AURKA was significantly associated with tumor grade (P<0.05) and poor histologic differentiation (P<0.05). The recurrence rate also tended to be high in cases with overexpression of AURKA (P<0.1) and these cases also had a tendency for shorter disease-free survival (DFS) (P<0.1). AURKA inhibition in endometrial cancer cell lines significantly decreased cell growth, invasion and migration (P<0.05), and increased chemosensitivity to paclitaxel. We also evaluated the efficacy of a combination of AURKA siRNA and paclitaxel against subcutaneous tumors formed in a nude mouse. After treatment, the tumor volume shrank significantly compared to treatment with paclitaxel only (P<0.05). To our knowledge, this is the first study in endometrial carcinoma to show a correlation between overexpression of AURKA and tumor grade, histological type and sensitivity to paclitaxel. AURKA is a promising therapeutic target in endometrial cancer and the combination therapy with AURKA inhibitors and paclitaxel could be effective for endometrial cancer that is resistant to conventional treatment and has a poor prognosis. PMID:25625960

  6. The eastern limit of Acadian high grade metamorphism in northern New England: Implications for the location of the Acadian Suture''

    SciTech Connect

    West, D.P. Jr. . Dept. of Geological Sciences)

    1993-03-01

    Identifying the eastern limit of Acadian high grade metamorphism in New England is complicated by the presence of pre-Devonian high grade relics, locally intense Late Paleozoic thermal overprints, and post-metamorphic faults. New [sup 40]Ar/[sup 39]Ar mineral ages from along the eastern margin of high grade metamorphism in Maine and New Hampshire help delineate the eastern limit of Devonian amphibolite facies metamorphism thereby placing constraints on the location of the Acadian suture. In New Hampshire, Acadian high grade metamorphism extends southeast at least as far as the Campbell Hill fault and perhaps as far as the Flint Hill fault. New [sup 40]Ar/[sup 39]Ar hornblende ages and previously published U-Pb monazite ages from the Massabesic Gneiss Complex are Permian indicating high grade Alleghanian metamorphism. New [sup 40]Ar/[sup 39]Ar hornblende ages from the Rye Formation, although complicated by excess argon, are considerably older, indicating an earlier Pre-Silurian amphibolite facies metamorphism affected these rocks. North of Portland, [sup 40]Ar/[sup 39]Ar hornblende ages east of the Norumbega Fault Zone from high grade rocks of the Casco Bay Group have ages that range from Middle Devonian to Early Carboniferous, consistent with diachronous cooling following Acadian metamorphism. Further northeast, in upper amphibolite facies rocks of the Passagassawakeag Gneiss, new [sup 40]Ar/[sup 39]Ar hornblende ages range from 385--395 Ma suggesting that these rocks were also affected by high grade Acadian metamorphism.

  7. microRNAs and Endometrial Pathophysiology.

    PubMed

    Chill, Henry H; Dior, Uri P; Kogan, Liron; Revel, Ariel

    2015-01-01

    Embryo implantation requires a reciprocal interaction between the blastocyst and endometrium and is associated with complex regulatory mechanisms. Since their discovery, microRNAs became prominent candidates providing missing links for many biological pathways. In recent years, microRNAs were implicated as one of the important players in regulation of various biological and physiological endometrial related processes. This chapter aims to present recent knowledge pertaining to the diverse aspects of microRNAs in the embryo-endometrial relationship. We will focus on the role of microRNAs in decidualization and their part in natural and stimulated cycles. Next, we will present recent studies deliberating the role of microRNAs in recurrent pregnancy loss and in the important phenomenon of recurrent implantation failure. Lastly, demonstrating an important aspect of embryo implantation and invasion, we will outline few microRNA related shared pathways of implantation and carcinogenesis. PMID:26662990

  8. Hysteroscopic assessment of postmenopausal endometrial thickening

    PubMed Central

    Solak, Neşe; Üstünyurt, Emin

    2014-01-01

    Introduction Endometrial thickness is measured by transvaginal sonography and thickening indicates an increased risk of malignancy or other pathology (hyperplasia or polyp) in the postmenopausal period. The main screening methods for the uterine cavity are dilatation and curettage, and hysteroscopy. We sought to correlate hysteroscopic and pathological findings in asymptomatic postmenopausal women with sonographically thickened endometrium (> 5 mm) in this study. Material and methods This retrospective cross-sectional study involved case records of 197 women who have thickened (> 5 mm) endometrium in the postmenopausal period. All these women underwent hysteroscopy with diagnostic dilatation and curettage between January 2012 and January 2013 at the Bursa Zübeyde Hanım Maternity Hospital. Sensitivity, specificity, positive, negative predictive values and p value of hysteroscopy were calculated. Dilatation and curettage was set as the gold standard. Results For the evaluation of postmenopausal thickened endometrium, hysteroscopy revealed sensitivity, specificity, positive predictive value and negative predictive value as 76.4%, 76.9%, 73.1%, 79.8%, respectively. Conclusions Hysteroscopy is a fast and accurate technique in evaluation of the intrauterine space occupying lesions (polyp, fibroid) but only moderate for endometrial hyperplasia. Hysteroscopic view combined with direct biopsy could be a gold standard for endometrial assessment. PMID:26327874

  9. Interstitial radiogold implantation for the treatment of recurrent high-grade gliomas

    SciTech Connect

    Larson, G.L.; Wilbanks, J.H.; Dennis, W.S.; Permenter, W.D.; Easley, J.D. )

    1990-07-01

    Thirty-three patients were treated at the Methodist Hospital, Baylor College of Medicine (Houston) between 1983 and 1987, for high-grade gliomas which had recurred after conventional external-beam radiation therapy. The mean dose to the tumor volume from the external-beam therapy was 5800 cGy. Thirteen patients had recurrent astrocytoma Grade 4 (glioblastoma), whereas 20 had recurrent astrocytoma Grade 3 (anaplastic astrocytoma). All patients were treated for their recurrence by the combination of reexcision of as much of the tumor mass as was technically feasible and intraoperative radiogold (198Au) seed implantation of the residual tumor and/or tumor bed. The mean dose to the tumor volume from the implant was 4000 cGy. For the 13 patients treated for recurrent glioblastoma the 1-year, 2-year, and 3-year survival rates were 46%, 15%, and 8%, respectively. For the 20 patients treated for recurrent anaplastic astrocytoma the 1-year, 2-year, and 3-year survival rates were 75%, 50%, and 15%, respectively. Survival was measured from the time of implant. The median survival for patients with glioblastoma was 9 months. The median survival for patients with anaplastic astrocytoma was 17 months. One patient died in the immediate postoperative period from a gastrointestinal bleed. No patient required reoperation for radiation necrosis. The authors believe that this technique is an effective treatment for patients with high-grade gliomas recurring after external-beam radiation therapy, and are now including interstitial irradiation in the initial management of selected patients with high-grade gliomas.

  10. Petrology and Geochronology of High-Grade Metamorphic Rocks from Cedros Island, Baja California, Mexico

    NASA Astrophysics Data System (ADS)

    Gonzales, D.; Leech, M. L.

    2014-12-01

    High-grade metamorphic rocks exposed on Cedros Island, Baja California, Mexico, record the Mesozoic subduction history of western North America. Blocks of amphibolite, blueschist, and eclogite crop out in a serpentinite-matrix mélange on the southeast and southwestern parts of Cedros Island. Amphibolite blocks contain Amp + Ep + Ab + Chl ± Ms ± Grt ± Ttn ± Qz; blueschist blocks have the assemblage Na-Amp + Ms + Lw + Qz ± Ttn ± Grt ± Jd ± Chl; and eclogite blocks are comprised primarily of Omp + Grt with retrograde Na-Amp + Ms + Lw. Blueschists from Cedros have been dated using 40Ar/39Ar step-heating of white mica and sodic amphiboles that yield ages from 103 ± 4 Ma to 94.9 ± 1.1 Ma, respectively, that represent cooling during exhumation. Apatite fission-track dating gives ages from 32 ± 4 Ma to 22 ± 3 Ma that record exhumation through the upper crust. Related Mesozoic subduction zone rocks of the Franciscan Complex crop out in a serpentinite-matrix mélange along coastal northern California. The Franciscan rocks are older, yielding 40Ar/39Ar step-heating ages of hornblende from amphibolite ranging from 159 to 156 Ma and represent an older part of the subduction history of the oceanic Farallon plate along western North America. I will determine the prograde and peak metamorphic P-T conditions for these high-grade rocks using petrography, mineral chemistries, and isochemical phase diagram modeling with Perple_X to generate complete P-T paths. I will then supplement these data with Sm-Nd and Lu-Hf geochronology for these high-grade Cedros rocks to evaluate their subduction/exhumation history, and develop a tectonic model for these southernmost Franciscan-type rocks. Ultimately, I will compare my results to Franciscan rocks in northern California to better understand the Mesozoic subduction margin of western North America.

  11. Role of Combined Circumareolar Skin Excision and Liposuction in Management of High grade Gynaecomastia

    PubMed Central

    Sarkar, Arindam; Bain, Jayanta; Bhattacharya, Debtanu; Sawarappa, Raghavendra; Munian, Kinkar; Dutta, Gouranga; Naiyer, Ghulam Jeelani; Ahmad, Shamshad

    2014-01-01

    Introduction: High-grade gynaecomastia (Simon IIb and III) has tissue excess (skin excess, enlarged areola, and displaced nipple), which is best managed surgically; however, results of conventional breast reduction surgeries and liposuction is not very good. Aim of our study was to describe a combined technique to manage these problems to produce a good result. Material and Method: This was a 2-year study among 12 patients of high grade gynaecomastia. Clinical and laboratory findings were normal. Pre-operatively in standing position, diameter of breast and areola, position of nipple, and amount of skin excess were marked. Under general anaesthesia, tumescent infiltration, circumareolar de-epithelisation of skin excess, and liposuction was completed. Redundant portion of the breast was sharply dissected and pulled out. Areola was fixed over pectoralis fascia at mid humerus level, just medial to the mid-clavicular line. Outer borders of the de-epithelised area were apposed by the purse-string effect of a subdermal suture, and further apposed by few half buried horizontal mattress sutures. Drains for 24 hour and compressive dressings for 6 weeks were used. Result: Mean age of presentation was 25.8 year; emotional discomfort was the chief complaint. Among 12 patients, 10 patients had bilateral gynaecomastia and 8 patients had enlarged and displaced nipple-areola complex. Average hospital stay was 2.41 days and recoveries were usually uneventful. Conclusion: The problem of tissue excess and tissue displacement in high grade gynaecomastia can be well managed by this combined circumareolar skin reduction and liposuction technique to achieve a scar-less flat male chest. PMID:25136214

  12. Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas

    PubMed Central

    2013-01-01

    Background High-grade soft tissue sarcomas are a heterogeneous, complex group of aggressive malignant tumors showing mesenchymal differentiation. Recently, soft tissue sarcomas have increasingly been classified on the basis of underlying genetic alterations; however, the role of aberrant DNA methylation in these tumors is not well understood and, consequently, the usefulness of methylation-based classification is unclear. Results We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines. The primary samples were partitioned into seven stable clusters. A classification algorithm identified 216 CpG sites, mapping to 246 genes, showing different degrees of DNA methylation between these seven groups. The differences between the clusters were best represented by a set of eight CpG sites located in the genes SPEG, NNAT, FBLN2, PYROXD2, ZNF217, COL14A1, DMRT2 and CDKN2A. By integrating DNA methylation and mRNA expression data, we identified 27 genes showing negative and three genes showing positive correlation. Compared with non-neoplastic fat, NNAT showed DNA hypomethylation and inverse gene expression in myxoid liposarcomas, and DNA hypermethylation and inverse gene expression in dedifferentiated and pleomorphic liposarcomas. Recovery of NNAT in a hypermethylated myxoid liposarcoma cell line decreased cell migration and viability. Conclusions Our analysis represents the first comprehensive integration of DNA methylation and transcriptional data in primary high-grade soft tissue sarcomas. We propose novel biomarkers and genes relevant for pathogenesis, including NNAT as a potential tumor suppressor in myxoid liposarcomas. PMID:24345474

  13. High-grade metamorphism of ironstones in the Mesoarchaean of southwest Swaziland

    NASA Astrophysics Data System (ADS)

    Horváth, Péter; Reinhardt, Jürgen; Hofmann, Axel

    2014-08-01

    A sequence of high-grade rocks collectively referred to as Mkhondo Valley Metamorphic Suite is exposed around the Nhlangano Gneiss Dome in southwest Swaziland and also less extensively further north. Meta-ironstones are part of this sequence and have been studied specifically with two main objectives in mind, firstly, to test the hypothesis of the high-grade metamorphic sequence correlating with lower-grade Pongola-age rocks nearby, and secondly, to assess the potential of these meta-ironstones for retrieving P-T conditions of metamorphism. The studied ironstones contain substantial Al due to terrigenous clastic input and also include Mn-rich varieties. Three compositional groups of meta-ironstones can be distinguished: garnet-orthopyroxene-bearing ones, garnet-bearing, orthopyroxene-free ones, and a garnet-poor to garnet-free type. A comparison of bulk rock compositions between these high-grade meta-ironstones and low-grade Mn-poor to Mn-rich ironstones from the Mozaan Group supports a stratigraphic correlation. Pseudosection modelling demonstrates that aluminous meta-ironstones provide useful P-T constraints at high peak temperatures as they do not tend to produce significant amounts of melt, if any. The presence of Al is critical for introducing garnet to amphibolite and granulite-facies assemblages, which also allows to apply conventional thermobarometers. The combination of pseudosection modelling and conventional thermobarometry yielded peak metamorphic conditions of 850-890 °C at 7 to 8 kbar. These data are compatible with the ones obtained from associated metapelitic gneisses, except that the latter indicate decompression to lower pressure granulite-facies conditions. The petrological, structural and geochronological data from southwest Swaziland confirm major orogenic activity in the eastern Kaapvaal Craton during the Neo-Archaean.

  14. Proliferative activity (ki-67 expression) and outcome in high grade osteosarcoma: a study of 27 cases.

    PubMed

    Jong, R; Davis, A M; Mendes, M G; Wunder, J S; Bell, R S; Kandel, R

    2000-01-01

    Purpose. Although pre-operative chemotherapy has improved the prognosis for individuals with osteosarcoma, approximately 40% of patients will die of their disease.The aim of this study was to quantitate proliferative activity in high grade osteosarcomas and to determine whether proliferation is a prognostic factor.Patients. The study consisted of 27 patients with high grade non-metastatic osteosarcoma at various sites for whom pre-operative biopsies and resection specimens were available for review. All patients were treated similarly and had at least 24 months' follow-up from the date of diagnosis.Methods. Proliferative activity (Ki-67 expression) was examined in the diagnostic biopsies immunohistochemically using the MIB-1 antibody. Proliferation was quantitated in two ways; (1) the number of immunopositive cells was counted manually using an ocular grid; or (2) the percentage of immunopositive nuclear area was assessed using morphometric image analysis. Proliferative index was evaluated in relation to patient outcome.Results. Proliferative activity was seen in all biopsies.The median proliferative index as determined by counting cells was 24% (mean of 27%, range of 7-61%) and by image analysis was 2% (mean 3%, range 0.32-8.4).The correlation between MIB-1 proliferation indices determined either by image analysis methodology or manual cell counting was high (Spearman's rho=0.79). Proliferative index did not appear to predict either disease-free or overall survival.Discussion. Tumor proliferation does not appear to be prognostic for high grade osteosarcomas.Whether assessment of this feature in conjunction with other tumor characteristics might be prognostic requires further study. PMID:18521434

  15. Diagnosis and Management of High-Grade Pancreatic Trauma: Report of 14 Cases.

    PubMed

    Bao, Wan-Yuan; She, Gang; Duan, Yun-Fei; Liu, Sheng-Yong; Sun, Dong-Lin; Yang, Yue; Zhu, Feng

    2015-12-01

    The aim of this study was to review the diagnosis and operative management of cases of high-grade pancreatic trauma. A retrospective analysis was performed on 14 patients treated for high-grade pancreatic trauma at our institution between December 2008 and November 2013. The patients were treated for injuries resulting from blunt abdominal trauma. The main clinical data of the patients was analyzed, including time to diagnosis, initial serum amylase level, ultrasonography and abdominal computed tomography (CT) findings, pancreatic injury severity as scored according to the American Association for the Surgery of Trauma Organ Injury Scale, injury to other organs, operative treatment method, postoperative complications, and patient outcome. All 14 patients were diagnosed with severe (≥ grade III) pancreatic trauma. Diagnosis was confirmed in all seven hemodynamically stable patients that underwent CT and in 9/13 patients receiving ultrasound examination. All patients underwent surgical operations, including emergency pancreaticoduodenectomy (n = 8), splenectomy with distal pancreatectomy (n = 3), spleen-preserving distal pancreatectomy (n = 1), medial pancreatectomy with Roux-en-Y pancreaticojejunostomy (n = 1), and peripancreatic debridement and drainage (n = 1). Diagnosis was delayed beyond 24 h in two patients, both of whom underwent reoperative peripancreatic debridement and drainage, with one death. The complications included pancreatic fistula (n = 8), peripancreatic abscess (n = 2), hepatic artery hemorrhage (n = 1), gastrointestinal bleeding (n = 1), and intra-abdominal abscess (n = 1). CT is the most reliable method for diagnosing high-grade pancreatic trauma. Aggressive surgical therapy including pancreaticoduodenectomy is acceptable in hemodynamically stable patients. PMID:27011541

  16. Evaluation of the hybrid capture 2 assay for detecting anal high-grade dysplasia.

    PubMed

    Goldstone, Stephen E; Lowe, Brian; Rothmann, Thomas; Nazarenko, Irina

    2012-10-01

    Hybrid Capture 2 (HC2) Human Papillomavirus (HPV) DNA Test® is FDA approved and is a proven aid in detecting HPV infections of the cervix and as an aid in diagnosing, with cytology, cervical disease. A prospective feasibility study was conducted to determine if HC2 testing has utility when screening for high-grade anal dysplasia (AIN2+). We enrolled 298 patients (45% HIV+) who had AIN2+ screening with cytology, histology and HC2 testing for two specimens: a swab into liquid-based cytology medium and either a swab or a brush collection in specimen transport medium (STM). High-resolution anoscopy was performed on all patients with biopsy of AIN2+ suspicious lesions. Cytology was benign (42%), atypical squamous cells of undetermined significance (30%), low-grade squamous intraepithelial lesion (18%), high-grade squamous intraepithelial lesion (1%), ASCUS possibly high-grade dysplasia (1.7%) and nondiagnostic (7%) and 36% had AIN2+ histology. Sensitivity and specificity for predicting AIN2+ histology for any abnormal cytology were 77 and 52%, whereas HC2 sensitivity and specificity were 91 and 40% (p = 0.005 for sensitivity), respectively. There was no significant difference in HC2 sensitivity or specificity between brush and swab or STM and residual cells from cytology. AIN2+ was found in 20% of patients with benign cytology. Only nine AIN2+ specimens were HC2-. This prospective study indicates that HC2 may be useful when screening for anal dysplasia; however, a larger study is recommended. PMID:22234750

  17. Serous carcinoma of endometrium in combination with neuroendocrine small-cell: A case report and literature review.

    PubMed

    Brudie, Lorna A; Khan, Faizan; Radi, Michael J; Ahmad, Sarfraz

    2016-08-01

    Endometrial serous carcinomas are very clinically aggressive, which constitutes 40% of all deaths and recurrences associated with endometrial cancer. Small-cell carcinoma of the endometrium is relatively rare but aggressive, and often presents a component of endometrioid carcinoma, and is not generally associated with serous carcinoma. Herein, we report a case of 74-year-old African-American female, who presented with intermittent post-menopausal bleeding for > 1-month. She underwent robotic-assisted laparoscopic hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node mapping, and pelvic-and-aortic lymphadenectomy. Final pathology was consistent with serous carcinoma of the endometrium in combination with neuroendocrine small-cell carcinoma. This extremely rare combination of tumors presents a challenge for treatment. The mainstay of treatment seems to be surgery followed by chemotherapy ± radiation therapy. To our knowledge, it represents an under-reported area of gynecological medicine. PMID:27508271

  18. Isolated third nerve palsy: A rare presentation of high grade glioma.

    PubMed

    Singh, Deepak Kumar; Singh, Neha; Singh, Ragini

    2016-01-01

    High grade gliomas account for almost one-third of primary central nervous system neoplasm, mainly in adults with a mean age of 41 years. They usually present with symptoms of raised intracranial pressure such as headache, vomiting, and seizures. We report a case of 55-year-old male presenting with right side complete third nerve palsy. Magnetic resonance imaging revealed an intraaxial tumor of the right medial temporal lobe. The tumor was removed grossly, and the histological diagnosis was anaplastic astrocytoma (WHO grade 3). We discuss clinical presentation of this case along with pertinent literature. PMID:27057228

  19. Isolated third nerve palsy: A rare presentation of high grade glioma

    PubMed Central

    Singh, Deepak Kumar; Singh, Neha; Singh, Ragini

    2016-01-01

    High grade gliomas account for almost one-third of primary central nervous system neoplasm, mainly in adults with a mean age of 41 years. They usually present with symptoms of raised intracranial pressure such as headache, vomiting, and seizures. We report a case of 55-year-old male presenting with right side complete third nerve palsy. Magnetic resonance imaging revealed an intraaxial tumor of the right medial temporal lobe. The tumor was removed grossly, and the histological diagnosis was anaplastic astrocytoma (WHO grade 3). We discuss clinical presentation of this case along with pertinent literature. PMID:27057228

  20. Comprehensive Assessment and Classification of High-Grade B-cell Lymphomas.

    PubMed

    Behdad, Amir; Bailey, Nathanael G

    2016-03-01

    High-grade B-cell lymphomas (HGBCLs) are a heterogeneous group of neoplasms that include subsets of diffuse large B-cell lymphoma, Burkitt lymphoma, and lymphomas with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Morphologically indistinguishable HGBCLs may demonstrate variable clinical courses and responses to therapy. The morphologic evaluation and classification of these neoplasms must be followed by further genetic and immunophenotypic work-up. These additional diagnostic modalities lead to a comprehensive stratification of HGBCL that determines the prognosis and optimal therapy. This article reviews the well-established and emerging biomarkers that are most relevant to the clinical management of HGBCL. PMID:26940267

  1. Prostate cancer with a pseudocapsule at MR imaging: a marker of high grade and stage disease?

    PubMed

    Bonde, Apurva A; Korngold, Elena K; Foster, Bryan R; Westphalen, Antonio C; Pettersson, David R; Troxell, Megan L; Simko, Jeffry P; Coakley, Fergus V

    2016-01-01

    Clinicopathological correlates of prostate cancer associated with a pseudocapsule at T2-weighted magnetic resonance (MR) imaging are presented in a retrospective series of 15 patients. Of 15 tumors, 14 involved the peripheral zone. Extracapsular extension was seen in 14 cases. Tumor Gleason score was 8 or above in 12 of 15 cases, and ductal type adenocarcinoma was identified in 4 cases. Step section histopathological correlation (n=5) demonstrated that the pseudocapsule corresponded with dense compressive or reactive peritumoral fibrosis. A pseudocapsule around prostate cancer at T2-weighted MR imaging is a rare finding that appears to be associated with high grade and stage disease. PMID:27133669

  2. Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type.

    PubMed

    Karnezis, Anthony N; Wang, Yemin; Ramos, Pilar; Hendricks, William Pd; Oliva, Esther; D'Angelo, Emanuela; Prat, Jaime; Nucci, Marisa R; Nielsen, Torsten O; Chow, Christine; Leung, Samuel; Kommoss, Friedrich; Kommoss, Stefan; Silva, Annacarolina; Ronnett, Brigitte M; Rabban, Joseph T; Bowtell, David D; Weissman, Bernard E; Trent, Jeffrey M; Gilks, C Blake; Huntsman, David G

    2016-02-01

    Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of SCCOHTs harbour inactivating mutations in the chromatin remodelling gene SMARCA4 with concomitant loss of its encoded protein SMARCA4 (BRG1), one of two mutually exclusive ATPases of the SWI/SNF chromatin remodelling complex. To determine the specificity of SMARCA4 loss for SCCOHT, we examined the expression of SMARCA4 by immunohistochemistry in more than 3000 primary gynaecological tumours. Among ovarian tumours, it was only absent in clear cell carcinoma (15 of 360, 4%). In the uterus, it was absent in endometrial stromal sarcomas (4 of 52, 8%) and high-grade endometrioid carcinomas (2 of 338, 1%). Recent studies have shown that SMARCA2 (BRM), the other mutually exclusive ATPase of the SWI/SNF complex, is necessary for survival of tumour cells lacking SMARCA4. Therefore, we examined SMARCA2 expression and discovered that all SMARCA4-negative SCCOHTs also lacked SMARCA2 protein by IHC, including the SCCOHT cell lines BIN67 and SCCOHT1. Among ovarian tumours, the SMARCA4/SMARCA2 dual loss phenotype appears completely specific for SCCOHT. SMARCA2 loss was not due to mutation but rather from an absence of mRNA expression, which was restored by treatment with the histone deacetylase inhibitor trichostatin A. Re-expression of SMARCA4 or SMARCA2 inhibited the growth of BIN67 and SCCOHT1 cell lines. Our results indicate that SMARCA4 loss, either alone or with SMARCA2, is highly sensitive and specific for SCCOHT and that restoration of either SWI/SNF ATPase can inhibit the growth of SCCOHT cell lines. PMID:26356327

  3. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.

    PubMed

    Davis, Drew G; Siddiqui, Momin T; Oprea-Ilies, Gabriela; Stevens, Keith; Osunkoya, Adeboye O; Cohen, Cynthia; Li, Xiaoxian Bill

    2016-01-01

    GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation. PMID:26527523

  4. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    PubMed

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease. PMID:26267317

  5. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma

    PubMed Central

    Stronach, Euan A.; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H.; Browne, Alacoque; Magdy, Nesreen; Studd, James B.; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-01-01

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease. PMID:26267317

  6. Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer

    PubMed Central

    Church, David N.; Stelloo, Ellen; Nout, Remi A.; Valtcheva, Nadejda; Depreeuw, Jeroen; ter Haar, Natalja; Noske, Aurelia; Amant, Frederic; Wild, Peter J.; Lambrechts, Diether; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T. H. B. M.; Creutzberg, Carien L.; Bosse, Tjalling

    2015-01-01

    Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided. Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06). Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in EC. PMID:25505230

  7. Expression and Functional Significance of HtrA1 Loss in Endometrial Cancer

    PubMed Central

    Mullany, Sally A.; Moslemi-Kebria, Mehdi; Rattan, Ramandeep; Khurana, Ashwani; Clayton, Amy; Ota, Takayo; Mariani, Andrea; Podratz, Karl C.; Chien, Jeremy; Shridhar, Viji

    2010-01-01

    Purpose The purpose of this study was to determine if loss of serine protease HtrA1 in endometrial cancer will promote the invasive potential of EC cell lines. Experimental design Western blot analysis and immunohistochemistry methods were used to determine HtrA1 expression in EC cell lines and primary tumors, respectively. Migration, invasion assays and in vivo xenograft experiment were performed to compare the extent of metastasis between HtrA1 expressing and HtrA-1 knocked down clones. Results Western blot analysis of HtrA1 in 13 EC cell lines revealed complete loss of HtrA1 expression in all 7 papillary serous EC cell lines. Downregulation of HtrA1 in Hec1A and Hec1B cell lines resulted in a 3-4 fold increase in the invasive potential. Exogenous expression of HtrA1 in Ark 1 and Ark 2 cells resulted in 3-4 fold decrease in both invasive and migration potential of these cells. There was an increased rate of metastasis to the lungs associated with HtrA1 downregulation in Hec1B cells compared to control cells with endogenous HtrA1 expression. Enhanced expression of HtrA1 in Ark 2 cells resulted in significantly less tumor nodules metastasizing to the lungs compared to parental or protease deficient (SA mutant) Ark 2 cells. Immunohistochemical (IHC) analysis showed 57% (105/184) of primary EC tumors had low HtrA1 expression. The association of low HtrA1 expression with high-grade endometrioid tumors was statistically significant (p=0.016). Conclusions Collectively, these data indicate loss of HtrA1 may contribute to the aggressiveness and metastatic ability of endometrial tumors. PMID:21098697

  8. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to h