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Int J Clin Exp Pathol 2011;4(5):444-453

Original Article
The proliferation markers Ki-67/MIB-1, phosphohistone H3, and survivin may contribute
in the identification of aggressive ovarian carcinomas

Guro Aune, Astrid K. Stunes, Solveig Tingulstad, Øyvind Salvesen, Unni Syversen, Sverre H. Torp

Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU),
Trondheim, Norway; Department of Gynecological Oncology, Department of Laboratory Medicine, Children’s and Women’s Health, St.Olavs
Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Endocrinology, St.Olavs Hospital, Trondheim University Hospital,
Trondheim, Norway; Department of Pathology and Medical Genetics, Department of Laboratory Medicine, Children’s and Women’s Health, St.
Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Received May 24, 2011; accepted June 10, 2011; Epub June 11, 2011; published June 20, 2011

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. (IJCEP1105005)

Keywords: Ovarian carcinoma, ovary, survival, Ki-67/MIB-1, PHH3, survivin, proliferation, diagnosis

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Address all correspondence to:
Guro Aune, MD
Faculty of Medicine
Department of Cancer Research and Molecular Medicine
PB 8905
N-7491 Trondheim, Norway
Tel: +47-72825272
Fax: +47-72571463
E-mail:
guro.aune@ntnu.no