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

• Published in: Head & neck Vol. 42; no. 11; pp. 3188 - 3196
• Main Authors: Holmes, Brittany J., Eyben, Rie, Attardi, Laura D., Kong, Christina S., Le, Quynh‐Thu, Nathan, Cherie‐Ann O.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-11-2020; Wiley Subscription Services, Inc
• Subjects: Apoptosis; Desmosomes; Genes, Tumor Suppressor; Head & neck cancer; head and neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - surgery; Humans; Immunohistochemistry; local recurrence; Margins of Excision; Membrane Proteins - genetics; Mucosa; Neoplasm Recurrence, Local - genetics; p53 Protein; Peripheral myelin protein 22; PERP; Pilot Projects; Prospective Studies; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - surgery; surgical margin; Tumor Suppressor Protein p53 - genetics; local recurrence; head and neck cancer; PERP; surgical margin; squamous cell carcinoma
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.26358

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.