Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas

TLDR

EGFR gene copy‑number gain is linked to poor prognosis in lung cancer, but its prognostic relevance in head and neck squamous cell carcinoma has not been previously reported. The study aimed to characterize EGFR status—including copy number, mutations, RNA, and protein expression—in 86 HNSCC tumors to inform the potential use of EGFR inhibitors. Researchers performed FISH to assess EGFR copy number, PCR and sequencing for activating mutations, and DNA microarray and immunohistochemistry to evaluate RNA and protein expression. Forty‑three of 75 evaluable tumors (58%) exhibited EGFR high polysomy or amplification, which was not associated with demographic or expression differences but correlated with significantly worse progression‑free and overall survival and higher ECop expression, demonstrating that EGFR copy‑number gain is a frequent poor‑prognosis marker in HNSCC.

Abstract

High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC.EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points.Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors.High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.