Pilot study of loss of the p53/p63 target gene PERP at the surgical margin as a potential predictor of local relapse in head and neck squamous cell carcinoma

Abstract Background PERP (p53 apoptosis effector related to PMP22) localizes to desmosomes and suppresses squamous cell carcinoma development. Loss of PERP leads to worse local control in head and neck squamous cell carcinoma (HNSCC), likely by destabilizing desmosomes. We evaluated PERP loss at HNSCC surgical margins as a predictor of local relapse. Methods Combining discovery (n = 17) and validation (n = 31) cohorts, we examined membranous PERP protein expression by immunohistochemistry in surgical mucosal margins with competing risk analysis of the relationship between local relapse and PERP expression. Results Of the 44 analyzable patients, the 2‐year cumulative incidence of local relapse was 44.4% for the PERP‐negative group and 16.4% for the PERP‐positive group ( P = .01). A trend toward worse progression‐free survival ( P = .09) and overall survival ( P = .06) was observed with loss of PERP. Conclusions PERP loss at surgical margins is associated with higher risk of local recurrence in HNSCC, warranting further evaluation in a larger prospective study.