Gene Expression Patterns of Paired Bronchioloalveolar Carcinoma and Benign Lung Tissue

A variant of adenocarcinoma, bronchioloalveolar carcinoma (BAC), has increased in incidence since 1950 and now represents 2-14% of all lung cancers. There has been concomitant diminution in the proportion of squamous cell carcinoma, the most common form of primary lung cancer. The BAC form of adenocarcinoma occurs disproportionately in women, has an earlier age of onset than conventional pulmonary carcinoma, and is not linked to smoking. The increased incidence of BAC in both smokers and non- smokers suggests that BAC may have an environmental etiology other than smoking. To explore this possibility, we compared the patterns of gene expression in paired samples of tumor and normal lung tissue from 3 patients with a pathologic diagnosis of BAC. Characterization of the gene expression patterns of the paired tissue samples was performed by oligonucleotide microarray analysis of 12,000 known genes and expressed sequence tags (ESTs). We identified 12 genes that were up-regulated ≥2-fold in all 3 tumors and 6 genes that were down-regulated in all 3 tumors to ≤0.20 times the baseline. These findings suggest that large scale transcriptional profiling of BAC tumors may disclose a pattern of altered cellular expression in response to genetic changes, diseases, and environmental insult; such transcriptional profiling may aid in diagnosis and therapy. (received 29 June 2001; accepted 23 August 2001)