Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction

Changes in cell survival contribute to tumour development, influence tumour biology and its response to chemotherapy. p53 gene alterations should nega tively affect apoptosis by impaired p53-dependent apoptotic response. We lo oked for associations between spontaneous apoptosis, p53 gene mutation, p53 protein accumulation, growth fraction, bcl-2 expression and histological p arameters in 64 ovarian, four tubal and three peritoneal carcinomas. Apopto tic cells were detected with the TUNEL method. p53 gene Variants were detec ted by the single-strand conformation polymorphism and were sequenced direc tly. P53, Ki-67 and bcl-2 protein expressions were detected immunohistochem ically. A weighed multiple logistic regression model was applied. Apoptotic index (Al) ranged 0.02-0.18 (mean 0.11); proliferation index (PI) ranged 3 -90% (mean 54%). p53 gene mutations were present in 51, p53 protein accumul ation in 46, and diffuse bcl-2 expression in 29 of 71 tumours. The Al was p ositively associated with the presence of p53 gene mutation (P = 0.011). Ho wever, the PI included into the analysis did positively influence the Al (P = 0.02) and diminished the association with p53 gene mutation (P = 0.082). The Al was negatively associated with good histological differentiation (P = 0.0006), the serous tumour type (P = 0.002), and diffuse bcl-2 expressio n (P = 0.025). Strong bcl-2 expression was associated with endometrioid tum our type (P = 0.002). FIGO stage and p53 protein accumulation were the only parameters that influenced overall survival time. Thus, our results sugges t that histological tumour type and grade are major determinants of spontan eous apoptosis in ovarian carcinomas; p53 alterations do not adversely but rather positively affect spontaneous apoptosis by increasing growth fractio n. This, in turn, suggests p53-independency of spontaneous apoptosis in ova rian carcinomas. (C) 2000 Cancer Research Campaign.