Prognostic evaluation of tumour type and other histopathological characteristics in advanced epithelial ovarian cancer, treated with surgery and paclitaxel/carboplatin chemotherapy: Cell type is the most useful prognostic factor
ABSTRACT Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied.
Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas.
Median overall survival (OS) was 49 months for type I versus 45 for type II (p=0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p=0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information.
The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel.
- SourceAvailable from: Marianne Jetske Rutten
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- "The same controversies regarding prognosis are seen between studies analysing HLA-G expression in ovarian cancer. These controversies could be due to the fact that heterogeneous groups of patients were analysed  . As HLA-G is frequently expressed in high grade ovarian tumours and almost never in low grade tumours, the role of this molecule could be different within these tumour types . "
ABSTRACT: Aberrant expression of human leukocyte antigens (HLA) class I has prognostic importance in various cancers. Here, we evaluated the prognostic value of classical (A/B/C) and nonclassical (G/E) HLA expression in 169 high grade epithelial ovarian cancer samples and linked that to clinicopathological characteristics and survival. Expression of HLA-A, -B/C, or -E was not correlated with survival. Survival was prolonged when tumours expressed HLA-G (P = 0.008) and HLA-G was an independent predictor for better survival (P = 0.011). In addition, HLA-G expression was associated with longer progression-free survival (P = 0.036) and response to chemotherapy (P = 0.014). Accordingly, high expression of HLA-G mRNA was associated with prolonged disease-free survival (P = 0.037) in 65 corresponding samples. Elevated serum-soluble HLA-G levels as measured by enzyme-linked immunosorbent assay in 50 matched patients were not correlated to HLA-G protein expression or gene expression nor with survival. During treatment, sHLA-G levels declined (P = 0.038). In conclusion, expression of HLA-G is an independent prognostic factor for improved survival in high grade epithelial ovarian cancer and a predictor for platinum sensitivity.Research Journal of Immunology 05/2014; 2014:274584. DOI:10.1155/2014/274584
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ABSTRACT: Ovarian cancer is the leading cause of death from gynecological cancers. Primary treatment of advanced ovarian cancer (FIGO stages III and IV) until recently consisted of cytoreductive surgery and paclitaxel/carboplatin chemotherapy. The results of two randomized studies, showing prolongation of progression-free survival (PFS) by the addition of the anti-VEGF monoclonal antibody, bevacizumab, led to the approval of this agent for first-line treatment of this disease and indicate that angiogenesis is a promising therapeutic target. Angiogenesis is essential for oncogenesis but also the viability and expansion of ovarian cancer. Specifically, VEGF is involved in the formation of ascites and has a direct effect on ascites tumor cells as well as an immunosuppressive function. Apart from VEGF, PDGF, FGF and angiopoietins present a therapeutic interest. We are reviewing the results of published clinical studies using anti-angiogenic factors in advanced ovarian cancer.Critical reviews in oncology/hematology 05/2012; 84(3). DOI:10.1016/j.critrevonc.2012.04.002 · 4.05 Impact Factor
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ABSTRACT: Introduction: Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histologic subtype remains undetermined. Although these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. Methods: To explore the spectrum of genomic alterations common to mucinous tumors we carried out high-resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n = 20) and borderline tumors (n = 22). RESULTS: Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. CONCLUSIONS: This study is the largest and highest resolution analysis of mucinous benign and borderline tumors carried out to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways. Clin Cancer Res; 18(19); 5267-77. ©2012 AACR.Clinical Cancer Research 08/2012; 18(19):5267-5277. DOI:10.1158/1078-0432.CCR-12-1103 · 8.19 Impact Factor