p53 protein in endometrial cancer is related to proliferative activity and prognosis but not to expression of p21 protein

Expression of the tumor suppressor gene product p53 and the cyclin-dependent kinase inhibitor p21, which is transcriptionally activated by p53, was investigated and compared with patient survival in a retrospective longitudinal study of 202 cases of endometrial carcinoma. The median duration of follow-up was 4.3 years. P53 was observed immunohistochemically in 63 (31%) of the tumors and was found by univariate analysis to be related to reduced adjusted survival (p = 0.00028) and disease-free survival (p = 0.04). However, p53 expression was not found by multivariate analysis to be an independent prognostic factor when compared with FIGO stage, histologic grade, and proliferative activity, as determined by immunoreactivity for topoisomerase II alpha with the antibody Ki-S1. Overexpression of p53 was related to histologic grade (p < 0.00001), proliferative activity (p = 0.0071), and inversely to progesterone receptor content (p = 0.042). Immunohistochemical identification of p21 was investigated in 95 cases and found to be positive in 19 (39%) of 49 tumors with p53 overexpression and in 13 (28%) of 45 tumors without p53 overexpression (p = 0.28). Expression of p21 is therefore not related to p53 expression, nor was it found to be related to proliferative activity. Strong expression of p21 was observed in tumors negative for progesterone receptors (p = 0.0028). P53 in endometrial carcinoma is not associated with induction of the cell cycle inhibitor p21, but is associated with an enhanced proliferative activity. The findings of multivariate analysis suggest that the prognostic significance of p53 is related mainly to cell proliferation.