Prognostic significance of p53 and p21(waf1/cip1) immunoreactivity in epithelial cancers of the ovary.

Objectives: Theprognostic value of p53 expression in epithelial ovarian cancer remains unresolved. We hypothesized that prognosis may relate more to expression of p21(waf1/cip1), the major downstream effector of p53, which can also be induced through p53-independent mechanisms. We therefore studied the relationship of p53 and p21(waf1/cip1) expression in epithelial ovarian cancers to clinicopathological variables and prognosis.

Methods: Fixed, embedded tumors from 85 patients with untreated, primary epithelial ovarian cancer were immunostained with antibodies to p53 and p21(waf1/cip1). Expression was correlated with clinicopathological features and prognosis. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test for p53, p21(waf1/cip1), and all combinations of expression of the two markers.

Results: Sixty-two percent of tumors expressed p53, and 42% expressed p21(waf1/cip1). There was no correlation between p53 and p21(waf1/cip1) expression. Advanced stage, grade, age >/=50, and p53 expression were associated with worse disease-free survival. Patients whose tumors were p53(+)/waf1(-), however, had a particularly strong association with poorer disease-free survival when compared with other combinations of p53 and p21(waf1/cip1) expression (P = 0.003). Neither p53, nor p21(waf1/cip1), nor combinations of expression were independently related to survival when histology, age, stage, and differentiation were considered.

Conclusions: p53 expression in the absence of p21(waf1/cip1) expression is a better marker of poor prognosis than either p53 or p21(waf1/cip1) expression status alone in univariate analysis. Absence of independent prognostic significance may be related to the paucity of early stage cases in the current study.