Loss of chromosome arms 3p and 9p and inactivation of P16 (INK4a) in normal epithelium of patients with primary lung cancer

The accumulation of genetic alterations in the respiratory epithelium may g ive rise to cancer and often is accompanied by a series of histologic alter ations over a period of several years. Recent studies have identified some molecular alterations in histologically normal-appearing epithelium among p atients with lung cancer. To extend these observations, we investigated clo nal genetic alterations by using fluorescence in situ hybridization (FISH) analysis and immunohistochemistry in 69 biopsy samples of histologically no rmal-appearing bronchial epithelium from 22 patients with or without lung c ancer. Thirty-seven biopsy specimens from 13 patients were examined for los s of 3p14, and 48 biopsy specimens from 18 patients were examined for loss at 9p21 by FISH. P16(INK4a) expression was analyzed in 54 biopsy samples fr om 19 patients. In at least one biopsy specimen from five of the 13 patient s with primary lung cancer, FISH or immunohistochemistry detected loss of t he 3p14 or 9p21 region. In contrast, no alterations were detected for the s ame regions in the nine patients without primary lung cancer. Our results s upport the concept that the normal epithelial surface of large bronchi of p atients with lung cancer has molecular changes suggestive of the outgrowth of numerous clonal foci. (C) 2001 Wiley-Liss, Inc.