Apoptosis and apoptosis-related proteins in the epithelium of human ovarian tumors: immunohistochemical and morphometric studies

Background: The origin of malignant ovarian tumors is the subject of consid erable controversy, which may be resolved by elucidation of molecular mecha nisms of tumorigenesis. Therefore we have undertaken the study of apoptosis in these tumors. Methods: Apoptosis and the expression of its related proteins, Fas, Fas lig and (FasL), bcl-2 and p53, in epithelial cells of human ovarian tumors of d ifferent histological grades, were determined immunohistochemically and mor phometrically. Results: Apoptosis-related proteins were absent from ovarian epithelia of p atients afflicted with non-cancerous diseases. In ovarian tumors, the distr ibution of individual proteins varied, and depended on the grade and type o f tumor. Fas and Fast were highly expressed in all tumors, while epithelial cells expressing bcl-2 were abundant in benign tumors, but their numbers s ignificantly dwindled with the progression of malignancy. Cells expressing p53 were found in borderline tumors, and their numbers increased with malig nancy, inverse of bcl-2 expression. Apoptotic tumor cells were scarce in bo rderline tumors and abundant in carcinomas. Grouping apoptosis was found in approximately 60% of the carcinomas. Conclusions: The initial development of ovarian tumors is accompanied by hi gh epithelial expression of Fas, Fast and bcl-2 proteins, while apoptosis a nd p53 proteins are detected only at later stages of tumorigenesis.