Clinical Significance of p53 and p16(ink4a) Status in a Contemporary North American Penile Carcinoma Cohort

BACKGROUND - Because of the low incidence of penile carcinoma (PC), the value of p16(ink4a), p53, and human papilloma virus (HPV) infection status in clinical practice remains unclear. Herein, we report our experience with potential clinical utility of these markers in men with PC treated at our institution.

PATIENTS AND METHODS - Tissue microarrays of 57 cases of invasive penile squamous cell carcinomas were immunohistochemically stained for p16 and p53. HPV in situ hybridization (ISH) for high-risk subtypes was also performed. Association between marker status, nodal disease, overall (OS) and cancer-specific survival (CSS) were assessed.

RESULTS - p16 and HPV ISH were positive in 23 (40%) and 24 (42%) of the cohort, respectively. The proportion of warty, basaloid, or mixed warty basaloid tumor subtypes were significantly greater in the p16-positive patients (48% vs. 3%; P < . 01). p53 expression was negative in 31 (54%) cases. Only in p16-negative patients, positive p53 status was associated with pN+ disease (odds ratio, 4. 4 [95% confidence interval (CI), 1. 04-18. 6]). In Kaplan-Meier analysis, the unadjusted estimated OS was insignificantly longer in p16-positive patients (median OS, 75 vs. 27 months; P = . 27) and median CSS was not reached (P = . 16). In a multivariable Cox proportional hazard model, when controlling for pathological nodal status and adjuvant chemotherapy, p16 status was a significant predictor for improved CSS (hazard ratio, 0. 36 [95% CI, 0. 13-0. 99]). The worst CSS was seen in pN+ patients with double negative p16 and p53 expression (8 vs. 34 months; P = . 01).

CONCLUSIONS - In this current cohort, p53 and p16 status showed clinical utility in predicting nodal disease as well as survival.

Clinical genitourinary cancer. 2015 Dec 23 [Epub ahead of print]

Kamran Zargar-Shoshtari, Philippe E Spiess, Anders E Berglund, Pranav Sharma, Julio M Powsang, Anna Giuliano, Anthony M Magliocco, Jasreman Dhillon

Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. , Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.  Department of Biomedical Informatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. , Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. , Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. , Center for Infection Research in Cancer, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. , Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. , Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

PubMed

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