Microsatellite alteration in histologically normal lung tissue of patientswith non-small cell lung cancer

Microsatellite alteration (MSA) has been observed in a fraction of non-smal l cell lung cancer (NSCLC). Most prior studies regarding MSA in lung cancer have usually used adjacent non-malignant lung tissues as a source of const itutional DNA. However, these normal tissues might have genetic alterations because the entire field of bronchial tree is exposed to the same carcinog enic insult. The aim of this study was to search if MSA is present in the h istologically normal lung tissue of patients with NSCLC. Tumor and correspo nding normal lung tissue specimens were obtained from 70 patients with NSCL C. Normal lung tissue specimens were obtained from either the opposite end of resected surgical samples or as distant from the tumor as possible. They were examined histopathologically and confirmed as normal by H-E stain. Pa tients' peripheral lymphocytes were used as the source for the normal DNA. Sixteen markers on 3p and 9p (nine and seven markers, respectively) were us ed. MSA was detected in seven of 20 (35%) histologically normal lung tissue specimens at a frequency similar to that observed in tumor tissue (eight o f 30, 40%). Five cases showed MSA in both normal lung tissue and the corres ponding tumor. In these five cases, MSA in normal lung tissue was detected at the same microsatellite markers which MSA was detected in the correspond ing tumor. The number and size of novel bands in normal lung tissue was ide ntical to that in tumor tissue except in one case. In which case, the same pattern of MSA was found in both normal lung tissue and corresponding tumor tissue at two markers. However, at one marker, while one identical novel b and was detected in normal lung tissue and corresponding tumor tissue, anot her novel band was found only in tumor tissue. In two of 12 patients whose tumor was negative for the presence of MSA, MSA was detected in normal lung tissue. These results indicate that genetic alterations an widely distribu ted in the lung tissue of patients with lung cancer and provide considerabl e support for the field cancerization theory, Screening for MSA in resected normal lung tissue might be a new method to identity patients at high risk for developing second primary lung cancers. (C) 2000 Elsevier Science Irel and Ltd. All rights reserved.