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

Head Neck. 2020 Nov;42(11):3188-3196. doi: 10.1002/hed.26358. Epub 2020 Jul 7.

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.

Keywords: PERP; head and neck cancer; local recurrence; squamous cell carcinoma; surgical margin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genes, Tumor Suppressor
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / surgery
  • Humans
  • Margins of Excision
  • Membrane Proteins / genetics
  • Neoplasm Recurrence, Local / genetics
  • Pilot Projects
  • Prospective Studies
  • Squamous Cell Carcinoma of Head and Neck / surgery
  • Tumor Suppressor Protein p53* / genetics

Substances

  • Membrane Proteins
  • PERP protein, human
  • Tumor Suppressor Protein p53