Prognostic value of proliferative activity of ovarian carcinoma as revealed by PCNA and AgNOR analyses.

Abstract

Proliferative activity of a malignant tumor is known to reflect its biologic aggressiveness. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation, and silver-stained nucleolar organizer regions (AgNORs) have been shown to correlate with ploidy and proliferative activity of cells depending on the method of assessment; the mean number of AgNORs per nucleus reflects ploidy, whereas the mean percentage of nuclei with five or more AgNORs per nucleus indicates proliferative activity. In ovarian carcinoma, the prognostic value of these markers has not been well defined. We studied PCNA expression and the AgNOR count in 43 ovarian carcinomas (25 serous, 13 mucinous, and 5 clear cell types) to assess their potential prognostic significance compared with the stage of disease and histopathologic features of the tumors. Eight benign (four serous and four mucinous) and six normal ovarian tissues were also evaluated. A standard colloidal silver staining and an immunohistochemical method were used. The mean percentage of PCNA positivity (PCNA index), the mean number of AgNORs per nucleus (mAgNOR), and the mean percentage of nuclei with more than five AgNORs per nucleus (pAgNOR) for each lesion were determined. In univariable analysis, PCNA indexes and mAgNOR and pAgNOR values were significantly higher in benign ovarian tumors compared with normal ovarian tissues and in adenocarcinomas compared with benign ovarian tumors. In multivariable analysis, PCNA indexes were significantly associated with histologic grade (P=.003), whereas associations of mAgNOR and pAgNOR values were highly significant with both histologic grade and disease stage (P=.0001). Histologic grade, but not subtype, was also associated with disease stage at a significant level (P=.008). Our findings indicate that differences in biologic behavior of ovarian carcinomas may, in part, be defined by differences in their ploidy and proliferative activity, and that whereas PCNA expression is of limited value, assessment of AgNORs holds promise in providing valuable prognostic information on the biologic behavior of the tumors.