Ki67 Antigen Immunostaining (MIB 1 Monoclonal Antibody) in Serous Ovarian Tumors: Index of Proliferative Activity with Prognostic Significance

Abstract

The purpose of this study was to evaluate the biological significance of Ki67 antigen expression in serous ovarian tumors, through the analysis of MIB 1 monoclonal antibody reactivity in cystoadenomas, borderline tumors, and invasive cystoadenocarcinomas; the correlation between this index of cell proliferation and clinicopathologic parameters (FIGO stage and grade, and disease-free survival) was also investigated in invasive cystoadenocarcinomas. Fifty-four patients with serous ovarian tumors, treated at the Institute of Gynecologic and Obstetrics, Ancona University, Italy, were used as study population; 10 women had serous cystoadenoma, 16 women had serous borderline tumor, and 28 women had invasive cystoadenocarcinoma. The expression of primary tumor proliferation related to Ki67 antigen was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. Compared to cystoadenomas and borderline tumors, the tissular Ki67 antigen immunostaining was significantly higher in cystoadenocarcinomas, with the highest values in architectural grade 2 and 3 neoplasms ( P < 0.001). Within the cystoadenocarcinomas, a relationship was observed between the measured proliferation index and disease FIGO stage, but it was not significant ( P = 0.92). However, patients who recurred and/or had disease progression presented a primitive neoplasm with significantly higher expression of Ki67 antigen than that of patients with disease-free survival ( P = 0.01). A significant relationship was observed between the Ki67 index and disease-free survival, independent of histologic grade and stage, evaluated by Cox hazards analysis ( P = 0.02). The proliferation index detected by Ki67 antigen immunostaining may represent an indicator of aggressiveness in serous ovarian tumors and an additionally useful prognostic factor in cystoadenocarcinomas, probably independent of and apparently more significant than the tumor architectural grade and the disease FIGO stage.