Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles

Molecular classification of tumors based on their gene expression profiles promises to significantly refine diagnosis and management of cancer patient s. The establishment of organ-specific gene expression patterns represents a crucial first step in the clinical application of the molecular approach. Here, we report on the gene expression profiles of 154 primary adenocarcin omas of the lung, colon, and ovary. Using high-density oligonucleotide arra ys with 7129 gene probe sets, comprehensive gene expression profiles of 57 lung, 51 colon, and 46 ovary adenocarcinomas were generated and subjected t o principle component analysis and to a cross-validated prediction analysis using nearest neighbor classification. These statistical analyses resulted in the classification of 152 of 154 of the adenocarcinomas in an organ-spe cific manner and identified genes expressed in a putative tissue-specific m anner for each tumor type. Furthermore, two tumors were identified, one in the colon group and another in the ovarian group, that did not conform to t heir respective organ-specific cohorts. Investigation of these outlier tumo rs by immunohistochemical profiling revealed the ovarian tumor was consiste nt with a metastatic adenocarcinoma of colonic origin and the colonic tumor was a pleomorphic mesenchymal. tumor, probably a leiomyosarcoma, rather th an an epithelial tumor. our results demonstrate the ability of gene express ion profiles to classify tumors and suggest that determination of organ-spe cific gene expression profiles will play a significant role in a wide varie ty of clinical settings, including molecular diagnosis and classification.