Correlation between morphological heterogeneity and genetic alteration within one tumor in adenocarcinomas of the lung

In some human cancers, multistep carcinogenesis has been advocated on the basis of morphological and genetic analysis. In adenocarcinoma of the lung, a carcinogenetic process from atypical adenomatous hyperplasia (AAH) to bronchiolo-alveolar carcinoma (BAC) and/or more malignant adenocarcinoma has been recently suggested. In the present study, we selected 13 lung tumors which had AAH-like or BAC-like areas at the periphery, and poorly differentiated areas at other sites, and examined their loss of heterozygosity (LOH) on chromosome 3p, 9p and 17p and point mutation of the p53 gene. A heterogeneous pattern of LOH and/or point mutation of the p53 gene was detected in five of 13 cases, and genetic alterations were frequent in the areas of poorer differentiation. These findings suggest that some adenocarcinomas of the lung occur through multistep carcinogenesis.