p16INK4a is a Marker of Good Prognosis for Primary Invasive Penile Squamous Cell Carcinoma: A Multi-Institutional Study

PurposeWe assessed the prognostic role of p16INK4a expression in penile cancer with respect to cancer specific survival.Materials and MethodsBased on a multi-institutional collaboration wax embedded tissues from 92 surgically treated patients, including 27 with total and 65 with partial penectomy, were retrospectively evaluated. After a central histopathological review by 1 pathologist a tissue microarray was constructed for p16INK4a immunostaining. Two independent pathologists evaluated p16INK4a expression, which was correlated with cancer specific survival. The κ statistic was used to assess interobserver variability. Univariate and multivariate Cox proportional hazards analysis was applied to assess the independent effects of prognostic factors on cancer specific survival during a median postoperative followup of 32 months (IQR 6–66).ResultsThe κ statistic revealed excellent interobserver agreement (κ 0.934, p <0.001). Two and 5-year cancer specific survival rates for the entire study cohort were 86% and 74%, respectively. The 2 and 5-year rates for patients without and with p16INK4a expression differed significantly (73% and 57% vs 95% and 85%, respectively, p = 0.011). Univariate analysis revealed p16INK4a expression as a significant prognostic factor with respect to cancer specific survival (p = 0.018). Multivariate analysis identified koilocytosis (HR 0.24, 95% CI 0.07–0.83, p = 0.024), p16INK4a expression (HR 0.44, 95% CI 0.23–0.84, p = 0.013), and histological stage (HR 3.54, 95% CI 1.88–6.67, p <0.001) and grade (HR 2.47, 95% CI 1.00–6.09, p = 0.049) as independent prognostic factors for cancer specific survival.ConclusionsResults show that p16INK4a seems to be a prognostic parameter for primary invasive penile cancer with excellent interobserver reproducibility. At pathology laboratories without antibodies against p16INK4a conventional histological determination of koilocytosis by the pathologist also appears to provide important prognostic information for cancer specific survival.