Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas.

Chung CH, Ely K, McGavran L, Varella-Garcia M, Parker J, Parker N, Jarrett C, Carter J, Murphy BA, Netterville J, Burkey BB, Sinard R, Cmelak A, Levy S, Yarbrough WG, Slebos RJ, Hirsch FR
J Clin Oncol. 2006 24 (25): 4170-6

PMID: 16943533 · DOI:10.1200/JCO.2006.07.2587

PURPOSE - 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.

PATIENTS AND METHODS - 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.

RESULTS - 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.

CONCLUSION - 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.

MeSH Terms (25)

Aneuploidy Carcinoma, Squamous Cell Disease-Free Survival DNA Mutational Analysis ErbB Receptors Female Gene Amplification Gene Deletion Gene Dosage Gene Expression Regulation, Neoplastic Head and Neck Neoplasms Humans Immunohistochemistry In Situ Hybridization, Fluorescence Male Middle Aged Multivariate Analysis Neoplasm Staging Oligonucleotide Array Sequence Analysis Predictive Value of Tests Prognosis Proportional Hazards Models Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Survival Analysis

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