Purpose: p53 and bcl-2 are important determinants of apoptosis. Inactivation of p53 by mutation often results in high expression of bcl-2 that is known to block apoptotic pathways and may thus lead to chemo- or radioresistance. However, bcl-2 may also be activated by p53-independent mechanisms which are not fully understood. This study was initiated to evaluate the coexpression of p53 and bcl-2 in advanced human epithelial ovarian (EOC) and endometrium carcinomas (ENC).Methods: A total of 24 samples derived from patients advanced EOC (n = 18) or ENC (n = 6) were studied by immunohistochemistry. Antigen recovery in paraffin-embedded sections was performed using standard techniques. P53 and bcl-2 were detected by primary monoclonal mouse anti-human antibodies in conjunction with red APAAP stain. Antigen-expression of 3 100 tumor cells per sample was evaluated by light-microscopy.Results: In only 3 of 18 EOC (17%) and 1 of 6 ENC (17%) 10-90% of tumor cells were positively stained for p53. In contrast, 10-90% bcl-2-expressing tumor cells were found in 17 of 18 EOC (94%) and 5 of 6 ENC (83%). Samples with high expression of p53 (i. e. > 50%) were also highly positive for bcl-2, whereas all bcl-2 negative specimens were found to carry wild-type p53.Conclusion: In a substantial proportion of advanced EOC and ENC, bcl-2 appears to be activated by p53- independent pathways.