Expression of P53 and Prognosis in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Lahin Amlani,Katie Zarins,Matthew Spector,Ariane Nguyen,Joshua Smith,Daffyd Thomas,Jonathan Mchugh,Jeremy Taylor,Gregory Wolf T,Emily Bellile,Chad Brenner,Laura Rozek

doi:10.23937/2378-3419/1410122

Abstract

Mutation of TP53 is the most common genetic abnormality in head and neck squamous cell carcinoma (HNSCC) and results in an accumulation and expression of p53 protein in tumor cells. Disruptive TP53 mutations are consistently associated with poor prognosis but correlations of p53 expression with mutation or prognosis have been variable and the usefulness of p53 as a target for immunotherapy is unknown. Favorable prognosis is associated with the accumulation of T lymphocytes (TILs) in the tumor microenvironment and an immune response to p53 has been suggested by demonstration of antibodies to p53 and p53-restricted cytotoxic cells in patients with HNSCC.

Highlights

Mutation of TP53 is the most common genetic abnormality in head and neck squamous cell carcinoma (HNSCC) and results in an accumulation and expression of p53 protein in tumor cells
Higher p53 protein expression was associated with worse overall survival (OS) in univariable (HR = 1.05; 95% C.I. = 1.02, 1.09; p = 0.002) but not in multivariable analysis and did not correlate with increased tumor infiltrating lymphocytes (TILs) infiltration
Further analysis by specific tumor site was unremarkable for an association between p53 expression and TILs or prognosis

Summary

Introduction

Mutation of TP53 is the most common genetic abnormality in head and neck squamous cell carcinoma (HNSCC) and results in an accumulation and expression of p53 protein in tumor cells. Mutations of the gene most commonly involve a missense mutation involving the p53 DNA-binding domain that leads to a change in the binding properties or conformation of the protein that inactivates its function and frequently results in prolonged protein half-life and accumulation in the cytoplasm, allowing detection by immunohistochemistry in tumor cells [10]. These gene products have been thought to be excellent targets for immunotherapy [11]. Overexpression of p53 is an unreliable indicator of TP53 mutation because of other loss of function, dominant-negative or gain of function alterations, degradation of p53 by HPV-16 and other causes of post transcriptional modifications [12]

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