Prognostic Factors for Stage III Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

Winter, William E.; Maxwell, G. Larry; Tian, Chunqiao; Carlson, Jay W.; Ozols, Robert F.; Rose, Peter G.; Markman, Maurie; Armstrong, Deborah K.; Fm, Muggia; McGuire, William P.

doi:10.1200/jco.2006.10.2517

Cited by 788 publications

(581 citation statements)

References 38 publications

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“…1,2 Some studies have showed that the endometrioid histology is associated with a better outcome than the serous histology. [2][3][4] In contrast, other studies have shown that when patients with endometrioid and serous tumors of the ovary are matched for age, tumor grade, disease stage, and level of cytoreduction, there is no difference in either the rate of 5-year survival or the mean/median length of survival. 5 The most commonly used grading systems have been those of the International Federation of Gynecology and Obstetrics (FIGO), the World Health Organization (WHO), and the Gynecologic Oncology Group (GOG).…”

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confidence: 93%

Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

et al. 2010

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Mutations in the b-catenin gene are common in ovarian endometrioid carcinoma. Few studies have addressed the association of b-catenin expression with tumor characteristics and patient outcome, yielding controversial results. The purpose of this study was to retrospectively assess the expression of b-catenin in ovarian endometrioid carcinoma and correlate its expression with the Gynecologic Oncology Group's (GOG) grading system, clinicopathological characteristics, and patient survival. A total of 49 patients with primary ovarian endometrioid carcinoma were included in this study. A four-tier score grading system was used for the membranous staining (negative, weak, moderate, and strong) and the percentage of positive cells for the nuclear staining of b-catenin. The status of five morphometric parameters, nuclear morphology (uniform or pleomorphic), mitotic count, glandular pattern, degree of squamous differentiation, and status of papillary pattern, was assessed. We found that a low membranous expression of b-catenin and a high mitotic count (415 per 10 high-power fields) were significantly associated with poor prognosis and early recurrence of ovarian endometrioid carcinoma. In addition, cases with nuclear expression of b-catenin showed an intermediate overall survival risk and late disease recurrence. Young age at the time of diagnosis, advanced disease stage, and suboptimal debulking were among the clinical factors predicting poor survival and early disease recurrence. The presence of squamous differentiation, a papillary pattern or nuclear pleomorphism did not show any correlation with overall survival or disease-free survival. Low membranous expression of b-catenin and high mitotic count are poor prognostic indicators in patients with ovarian endometrioid carcinoma, whereas the GOG grading system showed no prognostic value. Our data suggest that there is a need to define a better grading system for ovarian endometrioid carcinoma. Molecular markers such as b-catenin and mitotic count could aid in defining this grading system.

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confidence: 93%

Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

et al. 2010

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“…Patients with stage I MuOC have a 5‐year survival rate of 91%, whereas patients with recurrent disease or those diagnosed in an advanced stage usually die of the disease. The prognosis is significantly worse for patients with advanced‐stage MuOC than for patients with other histological subtypes of advanced‐stage ovarian cancer 5. The reason for this appears to be related to the frequency of platinum resistance in patients with MuOC 6.…”

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confidence: 99%

Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

Liew

Huang

Weng

et al. 2018

Intl Journal of Cancer

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Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor survival outcome in recurrent and advanced stages. The role of type‐specific epigenomics and its clinical significance remains uncertain. We analyzed the methylomic profiles of 6 benign mucinous adenomas, 24 MuOCs, 103 serous type of epithelial ovarian cancers (SeOCs) and 337 nonepithelial ovarian cancers. MuOC and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of which exhibited low methylation in MuOC and were associated with the response to glucocorticoid, ATP hydrolysis‐coupled proton transport, proteolysis involved in the cellular protein catabolic process and ion transmembrane transport. Hierarchical clustering analysis showed that the profiles of MuOC were similar to colorectal adenocarcinoma and stomach adenocarcinoma. Genetic interaction network analysis of differentially methylated genes in MuOC showed a dominant network module is the proteasome subunit beta (PSMB) family. Combined functional module and methylation analysis identified PSMB8 as a candidate marker for MuOC. Immunohistochemical staining of PSMB8 used to validate in 94 samples of ovarian tumors (mucinous adenoma, MuOC or SeOC) and 62 samples of gastrointestinal cancer. PSMB8 was commonly expressed in MuOC and gastrointestinal cancer samples, predominantly as strong cytoplasmic and occasionally weak nuclei staining, but was not expressed in SeOC samples. Carfilzomib, a second‐generation proteasome inhibitor, suppressed MuOC cell growth in vitro. This study unveiled a mucinous‐type‐specific methylation profile and suggests the potential use of a proteasome inhibitor to treat MuOC.

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“…1,2 Factors that are believed to impact survival include patient age, performance status, preoperative CA125, volume of ascites, stage, grade, extent of cytoreductive surgery, chemotherapeutic agents, route of delivery, duration of treatment, histological subtype, host immune response, and specific genetic alterations, including BRCA mutations. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] There remains, however, limited ability to accurately prognosticate in patients with advanced stage high-grade serous carcinoma based on features of the primary tumor at the time of diagnosis.…”

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confidence: 99%

BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma

et al. 2012

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We characterized BRCA1 and BRCA2 status (mutation/methylation) in a consecutive series of cases of ovarian carcinoma in order to identify differences in clinicopathological features, molecular characteristics, and outcome between the pelvic high-grade serous cancers with (i) germline or somatic mutations in BRCA1 or BRCA2, (ii) methylation of BRCA1, and (iii) normal BRCA1 or BRCA2. In all, 131 women were identified prospectively, who were undergoing surgical staging and agreed to germline testing for BRCA1 and BRCA2 mutations. Histopathology, germline and somatic BRCA1 or BRCA2 mutations, BRCA1 methylation, and BRCA1 and BRCA2 mRNA expression levels distinguished four subgroups. In all, 103 cases were high-grade serous carcinoma and of these 31 (30%) had germline or somatic BRCA1 or BRCA2 mutations (20% BRCA1 and 10% BRCA2) (group 1), 21 (20%) had methylation of BRCA1 (group 2), and in 51 (50%) there was no BRCA loss (group 3). Group 4 consisted of 28 cases of non-high-grade serous, none of which had BRCA loss. BRCA1 and BRCA2 mRNA expression levels correlated with designated group (P ¼ 0.0008). Among high-grade serous carcinomas, there were no differences between groups 1-3 with respect to stage, ascites, CA125 level, platinum sensitivity, cytoreduction rate, neoadjuvant chemotherapy, or survival. Tumors with BRCA1 or BRCA2 mutations had increased immune infiltrates (CD20 and TIA-1) compared with high-grade serous without mutations (P ¼ 0.034, 0.027). TP53 expression differed between groups (Po0.0001), with abnormal TP53 expression in 49/50 tumors from groups 1 and 2. Wild-type TP53 expression was associated with worse outcome in high-grade serous (Po0.001). BRCA loss (mutation/methylation) is a common event in the pelvic high-grade serous (50%). TP53 abnormalities and increased immune cell infiltrates are significantly more common in high-grade serous with germline and somatic mutations in BRCA1 or BRCA2, compared with tumors lacking BRCA abnormalities.

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Prognostic Factors for Stage III Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

Abstract: Age, PS, tumor histology, and residual tumor volume were independent predictors of prognosis in patients with stage III EOC. These data can be used to identify patients with poor prognosis and to design future tailored randomized clinical trials.

Cited by 788 publications

References 38 publications

Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma

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