title: The proliferation markers Ki-67/MIB-1, phosphohistone H3, and survivin may contribute in the identification of aggressive ovarian carcinomas.
abstract: The identification of new proliferation markers could have clinical implications in ovarian carcinoma by stratifying patients for treatment and follow-up. The aim of this study was to evaluate the diagnostic and prognostic value of the proliferation markers Ki-67/MIB-1, phosphorylated histone H3 (PHH3), and survivin in epithelial ovarian tumors. Ninety women with a pelvic mass who underwent surgery at the Department of Gynecological Oncology were included: 68 ovarian carcinomas, 11 borderline tumors, and 11 ovarian cystadenomas. We performed mitotic count and immunohistochemical analyses of Ki-67/MIB-1, PHH3, and survivin, related to clinicopathological parameters. Uni- and multivariate analyses of five-year overall survival were performed. We found statistically significant correlations between mitotic count, Ki-67/MIB-1, PHH3, and survivin. The expression of all proliferation markers was significantly higher in the carcinomas than in the borderline and benign tumors (p<0.05). There was, however an overlap of indices between the different malignancy groups. Women with advanced stage cancers (FIGO stage III and IV) had significantly higher tumor expression of all markers compared to patients with early stage cancers (FIGO stage I and II). Women with advanced disease and complete chemotherapy response had higher Ki67/MIB-1 expression than women without complete chemotherapy response. All markers had an impact on survival in the univariate analyses. In the multivariate analysis, however, only age and stage of disease reached statistical significance as prognostic factors. In conclusion, the proliferation markers Ki-67/MIB-1, PHH3, and survivin are positively correlated with each other and with tumor grade, and may contribute in the identification of aggressive ovarian carcinomas.
authors: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science andTechnology (NTNU), Trondheim, Norway. guro.aune@ntnu.no
authors: Guro
authors: G
authors: Aune
authors: Astrid K
authors: AK
authors: Stunes
authors: Solveig
authors: S
authors: Tingulstad
authors: Oyvind
authors: O
authors: Salvesen
authors: Unni
authors: U
authors: Syversen
authors: Sverre H
authors: SH
authors: Torp
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000473:pathology* / Q000628:therapy; D049109:Cell Proliferation; D015853:Cysteine Proteinase Inhibitors / Q000032:analysis*; D005260:Female; D006657:Histones / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000628:therapy; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D006657:Histones; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D000077022:Survivin