P16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas

Abstract

Objective.Aberrant expression of the cell cycle kinase inhibitors p16, p21, and p27 has been associated with poor prognosis in a variety of human malignancies. Little is known, however, about their clinical impact in vulvar carcinoma patients. Thus, we analyzed a larger series of vulvar squamous cell carcinomas and compared the results with clinical outcome. Methods.A total of 224 vulvar squamous cell carcinomas were immunohistochemically investigated for expression of p16, p21, and p27 using the biotin–streptavidin–peroxidase method and the OptiMax Plus automated cell staining system. Results.High p16 (≥5%) positive nuclear immunostaining was found in 69 (31%) cases, high p21 (any staining) protein levels was detected in 95 (42%) cases, and low p27 (≤50% positive nuclei) staining was seen in 170 (76%) cases. High expression of p16 was related to lower patient age and low expression of p53. High expression of p16 indicated a better prognosis in the multivariate analysis (RR = 0.5, 95% CI = 0.2–1.0) and less risk of developing lymph node metastasis (OR = 0.3, 95% CI = 0.2–0.7). High level of p21 was significantly associated with shorter survival in patients staged FIGO I and II (RR = 3.4, 95% CI = 1.3–9.3). We found no significant correlation between the expression of p27 and any of the clinicopathological variables. Conclusions.Our study indicates a prognostic relevance for p16 and p21 immunoreactivity. Low level of p16 protein and high level of p21 protein were associated with a shorter disease-related survival. We did not find p27 protein expression to be useful as a prognostic indicator in vulvar carcinoma patients.