Chung CH et al. (2006) Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 24: 4170–4176

The EGFR gene is overexpressed in several forms of cancer. EGFR protects cancer cells from the cytotoxic effects of chemotherapy and radiotherapy, and EGFR inhibitors have a clinical benefit in a subset of patients with head and neck squamous cell carcinoma (HNSCC), increasing their response to radiotherapy and improving survival. Elucidating the EGFR pathway and identifying biomarkers for the disease will be crucial for predicting the treatment response to EGFR inhibitors and for patient selection.

Chung et al. analyzed 86 tumor samples from 82 patients with HNSCC. Fluorescence in situ hybridization (FISH), polymerase chain reaction and DNA sequence analysis, and DNA microarray analysis and immunohistochemistry, were used to determine the EGFR gene copy number, EGFR gene mutation, and EGFR RNA and protein expression, respectively. HNSCC patients with FISH-positive (EGFR high polysomy and/or gene amplification) tumors had shorter progression-free and overall survival than those with FISH-negative tumors (P <0.05 and P <0.01, respectively). No mutations in EGFR were found, but the expression of EGFR-coamplified and overexpressed protein (Ecop), which regulates the activity of nuclear factor kappa B, was increased in FISH-positive tumors. An increase in nuclear factor kappa B signaling is a marker of worse prognosis in HNSCC.

Although this study demonstrated an association between increased EGFR copy number and worse prognosis in HNSCC, the underlying molecular mechanism is unclear.