Originally published as JCO Early Release 10.1200/JCO.2009.23.1431 on September 28 2009

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Genetic Abnormalities of the EGFR Pathway in African American Patients With Non–Small-Cell Lung Cancer

From the Departments of Medicine, Pathology, and Biostatistics, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH; Department of Pharmacology, Yale University School of Medicine, New Haven, CT; Departments of Medicine and Pathology, University of Colorado Cancer Center, Aurora, CO; and Instituto Clinico Humanitas Istituto di Ricerca e Cura a Carattere Scientifico, Rozzano, Italy.

Corresponding author: Balazs Halmos, MD, Division of Hematology/Oncology, Columbia University, New York, NY 10032; e-mail: bh2376{at}columbia.edu.

Purpose Previous studies in non–small-cell lung cancer (NSCLC) have demonstrated a wide variation in responsiveness to epidermal growth factor receptor (EGFR) –targeting agents and in genetic aberrancies of the EGFR pathway according to ethnic background, most notably a higher frequency of activating EGFR mutations among East-Asian patients. We investigated the frequency of EGFR pathway aberrancies among African American patients with NSCLC, for whom limited information presently exists.

Patients and Methods EGFR fluorescent in situ hybridization (FISH) was performed on archived tissues from 53 African American patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21 and KRAS exon 2. Results were compared by multivariate analysis to an historical control cohort of 102 white patients with NSCLC.

Results African Americans were significantly less likely to harbor activating mutations of EGFR than white patients (2% v 17%; P = .022). Only one EGFR mutation was identified, a novel S768N substitution. EGFR FISH assay was more frequently positive for African Americans than for white patients (51% v 32%; P = .018). KRAS mutational frequency did not differ between the groups (23% v 21%; P = .409).

Conclusion African American patients with NSCLC are significantly less likely than white counterparts to harbor activating mutations of EGFR, which suggests that EGFR tyrosine kinase inhibitors (TKIs) are unlikely to yield major remissions in this population. Our findings add to a growing body of evidence that points to genetic heterogeneity of the EGFR pathway in NSCLC among different ethnic groups and that underscores the need for consideration of these differences in the design of future trials of agents that target the EGFR pathway.

Supported by a Young Clinical Scientist Award from the Flight Attendant Medical Research Institute (B.H.) and by Grant No. RSG-08-303-01-TBE from the American Cancer Society (B.H.).

Presented in part at the Chicago Multidisciplinary Symposium in Thoracic Oncology, November 13-15, 2008, Chicago, IL.

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

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