Jpn J Clin OncoI1998;28(4)240-244 I Original Articles I Analysis of Loss of Heterozygosity in Small Adenocarcinomas of

Background: Despite the manystudies of genetic alterations in advanced lungcarcinomas, few reports haveanalyzed earlystageadenocarcinoma of the lung. Methods: We focused on small pulmonary adenocarcinomas, classified according to recently proposed histological criteria (Noguchi M., et al. Cancer 1995;75:2844-52) which divided adenocarcinomas 2 cm or less in diameter into twogroups; one showing replacing growth of the pulmonary alveolar structure [A, localized bronchioloalveolar carcinoma (LBAC); B, LBACwith alveolar collapse; C, LBAC with active fibroblastic proliferation] and the other showing non-replacing growth (0, poorly differentiated adenocarcinoma). Ninety-four small pulmonary adenocarcinomas, including 40 of typeA and B, 30 of type C and 24 of type D, were examined for loss of heterozygosity (LOH) using microsatellite markers. Results: Thefrequencies of LOH were 19.8 % intypes A andB,26.8 % intypeC and32.7 % intype D tumors. There were nosignificant differences in the frequency of LOH on chromosomes 2p,3p, 9p and17qamong tumortypes. However, on 17p, thefrequency of LOH wassignificantly lowerfor types A andB than for typeC or D.Three out of sixtypeC tumors which were positive for LOH at several loci showed different LOH patterns in two areas (central and peripheral regions). Conclusions: Allelic losses were detected in very earlyadenocarcinomas and the frequency of LOHs onchromosome 17pincreased during malignant progression of the tumor. Heterogeneous genetic alterations weredemonstrated even in small pulmonary adenocarcinomas. Key words: adenocarcinoma-lung- early cancer- genetic alteration