The Clinical Importance of Ki-67, p16, p14, and p57 Expression in Patients With Advanced Ovarian Carcinoma

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Abstract
Summary: The present study addressed the impact of p14, p16, p57, and Ki-67 in a large cohort of uniformly treated patients with stage III ovarian cancer in relation to other clinicopathologic variables and prognosis. We immunohistochemically studied 171 primary tumors from previously untreated patients with advanced ovarian carcinomas for expression of Ki-67, p16, p14, and p57. High protein levels of Ki-67 (>10% positive nuclei) were found in 144 cases (84%), p16 (>50% positive nuclei) in 53 cases (31%), p57 (>10% positive nuclei) in 41 cases (24%), and p14 (any positive nuclei) in 19 cases (11%). A correlation between high Ki-67 expression and presence of residual disease after primary surgery (P = 0.019), ascites (P = 0.006), higher International Federation of Gynecology and Obstetrics substage (P < 0.001), poor differentiation (P < 0.001), and higher Silverberg histopathologic grade (P < 0.0001) was seen. High expression of p16 correlated to poor differentiation (P = 0.033) and higher Silverberg histopathologic grade (P = 0.018). In univariate analysis, high expression of Ki-67 (P = 0.0001) and p16 (P = 0.005) was associated with poor survival. However, in multivariate analysis, only high expression of Ki-67 was significantly associated with shorter survival (P = 0.025). No correlations were seen between expression of p14 and p57 and clinicopathologic parameters. None of the factors studied was able to predict response to chemotherapy. Our results showed that Ki-67 represents an independent prognostic predictor in stage III ovarian cancer. We did not find p16, p14, and p57 to be useful as prognostic markers.