bcl-2 Expression, p53 Accumulation, and Apoptosis in Ovarian Carcinomas

Abstract

Because little is known about the importance of apoptosis and its regulation in epithelial ovarian cancer, the authors looked for bcl-2 expression and p53 accumulation by immunohistochemistry in 148 ovarian carcinomas of different histologic types and stages. The number of apoptotic cells was assessed in situ by enzymatic detection of DNA fragmentation. Strong bcl-2 expression correlated with low histologic grade (P = .004) and was most often seen in endometrioid carcinomas (P = .001), whereas p53 accumulation was predominantly found in serous and undifferentiated carcinomas (P <.001) and high grade tumors (P <.001). p53 accumulation was associated with advanced tumor stage (P <.001) and the presence of residual disease after surgery (P <.001). Apoptosis increased with histologic grade (P = .012); apoptotic cells were sparse or absent in tumors of low malignant potential and mucinous carcinomas, but found in all other carcinoma types (P = .001). Apoptosis, bcl-2 expression, and p53 protein accumulation were not correlated with each other. The analysis of the postoperative course of 110 patients showed that survival depended on histologic tumor type (P = .0037), histologic grade (P = .0143), FIGO (International Federation of Gynecology and Obstetrics) stage (P = .0001), and the absence or presence of postoperative residual tumor mass (P = .0001). p53 accumulation was also associated with adverse prognosis (P = .0001). However, bcl-2 immunohistochemistry identified a subgroup of patients with p53 and bcl-2 positive carcinomas who had a statistically significantly better outcome than patients with p53 positive and bcl-2 negative tumors (P = .0443). Regarding FIGO stage and p53 alone in a Cox model, p53 proved to contribute additional prognostic information both in FIGO stages I/II as well as in FIGO stages III/IV. Thus, our observations point to different molecular alterations possibly underlying phenotypic diversity of ovarian carcinomas and provide clues for a better understanding of tumor progression in these neoplasms. Apoptosis plays a role in ovarian carcinomas, but seemingly is regulated in a different way than in nonneoplastic tissues.