P53 and bcl-2 in Epithelial Ovarian Carcinoma: Their Value as Prognostic Indicators at a Median Follow-up of 60 Months

Abstract

Objective. p53 is the most common tumor suppressor gene involved with human malignancies. Mutations in p53 are present in approximately 50% of human malignancies. bcl-2 is a protooncogene. Expression of its protein product is related to better prognosis in several malignancies.Methods. One hundred and three patients with epithelial ovarian carcinoma were studied. Immunohistochemical staining using the pAb1801 monoclonal antibody to p53 and the anti-bcl-2 124 monoclonal antibody to bcl-2 was performed. Image analysis was used to measure percentage positive nuclear area staining of mutant p53. In addition to bcl-2 and p53, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. Univariate as well as Cox regression analysis was performed.Results. One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO stage I disease, 4 stage II, 59 stage III, and 20 stage IV. Immunohistochemical staining for mutant p53 was not significantly related to DNA index (P = 0.99) but was related to increasing FIGO stage (P < 0.001) and increasing histologic grade (P = 0.039). Using Cox regression analysis, increased mutant p53 staining was an independent predictor of survival in these patients (P = 0.0032), along with stage (P < 0.0001) and level of cytoreduction (P < 0.0001). Although by itself bcl-2 was not an independent prognostic indicator (P = 0.18), the combination of p53 and bcl-2 was independently predictive of survival (P = 0.038).Conclusion. This study confirms the authors' earlier report on the importance of p53 as a prognostic indicator of survival in ovarian carcinoma. Cox regression analysis reveals mutant p53 staining to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than the combination of bcl-2 and p53.