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Epidermal Growth Factor Receptor Copy Number Alterations Correlate With Poor Clinical Outcome in Patients With Head and Neck Squamous Cancer

Stephane Temam, Hidetoshi Kawaguchi, Adel K. El-Naggar, Jaroslav Jelinek, Hongli Tang, Diane D. Liu, Wenhua Lang, Jean-Pierre Issa, J. Jack Lee, Li Mao

From the Molecular Biology Laboratory and Departments of Thoracic/Head and Neck Medical Oncology, Leukemia, Biostatistics, and Pathology, The University of Texas M.D. Anderson Cancer Center; and the Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX

Address reprint requests to Li Mao, MD, Department of Thoracic/Head and Neck Medical Oncology, Unit 432, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: lmao{at}mdanderson.org

Purpose Overexpression of epidermal growth factor receptor (EGFR) is common in head and neck squamous cell carcinoma (HNSCC). Recent studies showed that EGFR inhibitors are effective for patients with HNSCC. This study analyzed the genetic nature of EGFR gene in HNSCC and its clinical correlations.

Patients and Methods The EGFR gene copy numbers in 134 HNSCC tumors were determined using quantitative real-time polymerase chain reaction. The status of EGFR gene copy numbers was analyzed with clinical parameters including clinical outcome. Mutation status of EGFR exons 18, 19, and 21 was determined in the HNSCC tumors.

Results Aberrant EGFR copy numbers were found in 32 (24%) of 134 tumors, including 22 (17%) with increased copy number and 10 (7%) with decreased copy number. Patients whose tumors had EGFR copy number alterations (particularly patients with increased copy numbers) had significantly poorer overall, cancer-specific, and disease-free survivals compared with patients with normal copy numbers (P < .0001). At 5 years after initial diagnosis, 20 (91%) of the 22 patients with increased copy numbers died of disease compared with 30 (29%) of the 102 patients with normal copy number. No mutations on EGFR exons 18, 19, and 21 were detected in any of the tumors.

Conclusion A subset of HNSCC manifests EGFR copy number alterations, and this is associated with a poor clinical outcome, suggesting a biologic role of the alterations. The rare mutation or small deletion at EGFR exons 18 to 21 indicates a minimal role of these events in HNSCC.

Supported by National Cancer Institute Grants No. CA106451 and CA16672 and Department of Defense Grant No. W81XWH-05-2-0027.

S.T. and H.K. contributed equally to the work.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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