title: Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles.
abstract: Molecular classification of tumors based on their gene expression profiles promises to significantly refine diagnosis and management of cancer patients. 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 adenocarcinomas of the lung, colon, and ovary. Using high-density oligonucleotide arrays with 7129 gene probe sets, comprehensive gene expression profiles of 57 lung, 51 colon, and 46 ovary adenocarcinomas were generated and subjected to 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-specific manner and identified genes expressed in a putative tissue-specific manner 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 their respective organ-specific cohorts. Investigation of these outlier tumors by immunohistochemical profiling revealed the ovarian tumor was consistent with a metastatic adenocarcinoma of colonic origin and the colonic tumor was a pleomorphic mesenchymal tumor, probably a leiomyosarcoma, rather than an epithelial tumor. Our results demonstrate the ability of gene expression profiles to classify tumors and suggest that determination of organ-specific gene expression profiles will play a significant role in a wide variety of clinical settings, including molecular diagnosis and classification.
authors.affiliation: Department of Pathology, The University of Michigan, Ann Arbor, Michigan 48109-0054, USA. giordano@med.umich.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Giordano
authors.forename: K A
authors.initials: KA
authors.lastname: Shedden
authors.forename: D R
authors.initials: DR
authors.lastname: Schwartz
authors.forename: R
authors.initials: R
authors.lastname: Kuick
authors.forename: J M
authors.initials: JM
authors.lastname: Taylor
authors.forename: N
authors.initials: N
authors.lastname: Lee
authors.forename: D E
authors.initials: DE
authors.lastname: Misek
authors.forename: J K
authors.initials: JK
authors.lastname: Greenson
authors.forename: S L
authors.initials: SL
authors.lastname: Kardia
authors.forename: D G
authors.initials: DG
authors.lastname: Beer
authors.forename: G
authors.initials: G
authors.lastname: Rennert
authors.forename: K R
authors.initials: KR
authors.lastname: Cho
authors.forename: S B
authors.initials: SB
authors.lastname: Gruber
authors.forename: E R
authors.initials: ER
authors.lastname: Fearon
authors.forename: S
authors.initials: S
authors.lastname: Hanash
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D003110:Colonic Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor