Analysis of Loss of Heterozygosity in Small Adenocarcinomas of the Lung

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Abstract
Background: Despite the many studies of genetic alterations in advanced lung carcinomas, few reports have analyzed early stage adenocarcinoma 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 two groups; one showing replacing growth of the pulmonary alveolar structure [A, localized bronchioloalveolar carcinoma (LBAC); B, LBAC with alveolar collapse; C, LBAC with active fibroblastic proliferation] and the other showing non-replacing growth (D, poorly differentiated adenocarcinoma). Ninety-four small pulmonary adenocarcinomas, including 40 of type A and B, 30 of type C and 24 of type D, were examined for loss of heterozygosity (LOH) using microsatellite markers. Results: The frequencies of LOH were 19.8% in types A and B, 26.8% in type C and 32.7% in type D tumors. There were no significant differences in the frequency of LOH on chromosomes 2p, 3p, 9p and 17q among tumor types. However, on 17p, the frequency of LOH was significantly lower for types A and B than for type C or D. Three out of six type C 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 early adenocarcinomas and the frequency of LOHs on chromosome 17p increased during malignant progression of the tumor. Heterogeneous genetic alterations were demonstrated even in small pulmonary adenocarcinomas.