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Departments of 1 Thoracic/Head and Neck Medical Oncology, 2 Biostatistics and Applied Mathematics, 3 Thoracic Surgery, and 4 Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas and 5 Hamon Center for Therapeutic Oncology Research, Departments of 6 Internal Medicine, 7 Pharmacology, and 8 Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
Requests for reprints: Ignacio I. Wistuba, Department of Pathology, Unit 85, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009. Phone: 713-563-9184; Fax: 713-563-1848; E-mail: iiwistuba{at}mdanderson.org.
To determine whether EGFR tyrosine kinase domain mutations are early events in the pathogenesis of lung adenocarcinomas, we tested for the presence of EGFR mutations in histologically normal bronchial and bronchiolar epithelia from lung adenocarcinomas bearing the common EGFR mutations. DNA was extracted from microdissected tissue obtained from 21 tumors with known EGFR mutations, 16 tumors without mutation, and 90 sites of normal bronchial and bronchiolar epithelium from the same surgical specimens. With the use of PCR and direct DNA sequencing, EGFR mutations identical to the tumors were detected in the normal respiratory epithelium in 9 of 21 (43%) patients with EGFR mutant adenocarcinomas but none in patients without mutation in the tumors. The finding of mutations being more frequent in normal epithelium within tumor (43%) than in adjacent sites (24%) suggests a localized field effect phenomenon. Our findings indicate that mutation of the tyrosine kinase domain of EGFR is an early event in the pathogenesis of lung adenocarcinomas, and suggest EGFR mutations as an early detection marker and chemoprevention target.
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