Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses

We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 tra nscript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expres sion data defined distinct subclasses of lung adenocarcinoma. Among these w ere tumors with high relative expression of neuroendocrine genes and of typ e II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene express ion. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of ext ra-pulmonary origin. These results suggest that integration of expression p rofile data with clinical parameters could aid in diagnosis of lung cancer patients.