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      The prognostic value of Ki67 in ovarian high-grade serous carcinoma: an 11-year cohort study of Chinese patients

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          Abstract

          Objective

          This study sought to assess the prognostic role of Ki67 in primary ovarian high-grade serous carcinoma (HGSC) and to determine whether Ki67 expression can predict responsiveness to platinum and paclitaxel chemotherapy.

          Results

          A total of 318 women were included in the analysis and the median follow-up time was 48 months (range, 3–150 months). Ki67 proliferation indices ranged from 3% to 95% with a median of 40%. Using 40% as the cut-off value for the Ki67 index, we classified 141 patients as having low Ki67 expression and 177 patients as having high Ki67 expression. Low Ki67 expression was a predictor of platinum resistance (hazard ratio (HR) 2.85, 95% CI 1.43–5.98, P < 0.001). In the Kaplan-Meier analysis, comparisons of patients with low versus high Ki67 expression demonstrated that low Ki67 expression was significantly associated with decreased progression-free survival (PFS) (22% vs. 34% for 5-year PFS, P < 0.001) and decreased overall survival (OS) (31% vs. 55%, P < 0.001). Multivariate analysis indicated that low Ki67 expression was associated with decreased PFS (HR 2.98, 95% CI 1.75–6.56, P < 0.001) and decreased OS (HR 1.74, 95% CI 1.38–5.01, P = 0.003).

          Materials and Methods

          A retrospective study of patients with stage I-IV primary ovarian HGSC was conducted from January 1, 2002, to December 31, 2012. Ki67 levels were measured via immunohistochemistry (IHC) and analyzed with respect to clinicopathological factors, and a survival analysis was performed.

          Conclusions

          HGSC appears to be a heterogeneous disease with different clinical outcomes. Low Ki67 expression (< 40%) in HGSC is significantly associated with platinum resistance and decreased survival.

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          Most cited references20

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          Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015

          The 14th St Gallen International Breast Cancer Conference (2015) reviewed new evidence on locoregional and systemic therapies for early breast cancer. This manuscript presents news and progress since the 2013 meeting, provides expert opinion on almost 200 questions posed to Consensus Panel members, and summarizes treatment-oriented classification of subgroups and treatment recommendations.
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            The new FIGO staging system for ovarian, fallopian tube, and primary peritoneal cancer.

            Recent molecular research has revolutionized the understanding of ovarian cancer. It is now non-controversial that the term ovarian cancer summarizes a heterogenous group of malignant epithelial tumors. Findings of large clinical trials investigating surgical and systemic therapeutic approaches have defined the most important prognostic parameters. Therefore, the oncology committee of FIGO, headed by the South African gynecologic oncologist Lynette Denny, took the effort to revise the FIGO classification of ovarian cancer that was implemented in 1988.
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              Precursors and pathogenesis of ovarian carcinoma.

              The ultimate goal of defining cancer specific precursors is to facilitate early detection and intervention before the development of invasive malignancy. Unlike other malignancies involving the female genital tract such as cervical or endometrial carcinomas, precursor lesions of ovarian carcinomas have not been well characterised, resulting in a failure to develop effective screening programs. Recent clinicopathological and molecular studies have provided new insight into the origin and pathogenesis of ovarian carcinomas. It has been shown that ovarian cancer is comprised of different tumour types differing not only in morphology, but also in pathogenesis, molecular alterations and clinical progression. A dualistic model of ovarian carcinogenesis has been proposed. Type I tumours which include low grade serous, low grade endometrioid, clear cell, mucinous carcinomas and Brenner tumours, are generally indolent and tend to be genetically stable, although clear cell carcinoma would probably belong to an intermediate category. They demonstrate a step-wise progression from a benign precursor such as a benign to borderline tumour or endometriosis and are characterised by genetic aberrations targeting specific cell signalling pathways. Type II tumours comprise high grade serous, high grade endometrioid, and undifferentiated carcinomas as well as malignant mixed mesodermal tumours. They are clinically aggressive and exhibit high genetic instability with frequent p53 mutations. Mounting evidence suggests that many high grade serous carcinomas originate from the epithelium of the distal fallopian tube, and that serous tubal intraepithelial carcinoma (STIC) represents the putative precursor of these neoplasms. Low grade serous carcinomas arise via transformation of benign and borderline serous tumours, thought to be derived from inclusion cysts originating from the ovarian surface or tubal epithelium. Recently it has been suggested that papillary tubal hyperplasia may be a putative precursor lesion for serous borderline tumours. Both endometrioid and clear cell carcinomas develop from endometriosis, via alterations affecting different genetic pathways. The origin of mucinous and transitional cell neoplasms is not well characterised, although new data suggest a possible origin from transitional cell nests present at the tubal-mesothelial junction. Likewise, the pathogenesis of carcinosarcomas is also not well established because of their rarity but there is accumulating evidence that the carcinomatous component determines the course of the disease and gives rise to the malignant mesenchymal component. This review discusses recent developments in the pathogenesis of ovarian carcinoma, with particular emphasis on the putative precursor lesions that give rise to the major histological subtypes. Recognition of these lesions is not only important in improving the understanding of ovarian carcinogenesis, but it will also influence our approach to prevent, detect and treat these tumours.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                8 December 2017
                23 December 2016
                : 8
                : 64
                : 107877-107885
                Affiliations
                1 Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
                2 Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
                Author notes
                Correspondence to: Mian He, mianhe64@ 123456163.com
                Article
                14112
                10.18632/oncotarget.14112
                5746111
                29296209
                1d3f2526-6662-41e7-aeb1-ac1933de04b2
                Copyright: © 2017 Chen et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 August 2016
                : 19 October 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                high-grade serous ovarian cancer,ki67,platinum-resistance,survival,prognostic biomarker

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