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Patterns of Gene Expression in Different Histotypes of Epithelial Ovarian Cancer Correlate with Those in Normal Fallopian Tube, Endometrium, and Colon

Authors' Affiliations: Departments of ¹ Experimental Therapeutics, ² Biostatistics and Applied Mathematics, ³ Gynecological Oncology, ⁴ Molecular Therapeutics, and ⁵ Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas; ⁶ Mayo Clinic Cancer Center, Rochester, Minnesota; ⁷ New York University School of Medicine, New York, New York; and ⁸ Duke University Medical Center, Durham, North Carolina

Requests for reprints: Rebecca T. Marquez, Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Box 354, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-3790; Fax: 713-742-7864; E-mail: rtmarquez{at}mdanderson.org.

Purpose: Epithelial ovarian cancers are thought to arise from flattened epithelial cells that cover the ovarian surface or that line inclusion cysts. During malignant transformation, different histotypes arise that resemble epithelial cells from normal fallopian tube, endometrium, and intestine. This study compares gene expression in serous, endometrioid, clear cell, and mucinous ovarian cancers with that in the normal tissues that they resemble.

Experimental Design: Expression of 63,000 probe sets was measured in 50 ovarian cancers, in 5 pools of normal ovarian epithelial brushings, and in mucosal scrapings from 4 normal fallopian tube, 5 endometrium, and 4 colon specimens. Using rank-sum analysis, genes whose expressions best differentiated the ovarian cancer histotypes and normal ovarian epithelium were used to determine whether a correlation based on gene expression existed between ovarian cancer histotypes and the normal tissues they resemble.

Results: When compared with normal ovarian epithelial brushings, alterations in serous tumors correlated with those in normal fallopian tube (P = 0.0042) but not in other normal tissues. Similarly, mucinous cancers correlated with those in normal colonic mucosa (P = 0.0003), and both endometrioid and clear cell histotypes correlated with changes in normal endometrium (P = 0.0172 and 0.0002, respectively). Mucinous cancers displayed the greatest number of alterations in gene expression when compared with normal ovarian epithelial cells.

Conclusion: Studies at a molecular level show distinct expression profiles of different histologies of ovarian cancer and support the long-held belief that histotypes of ovarian cancers come to resemble normal fallopian tube, endometrial, and colonic epithelium. Several potential molecular markers for mucinous ovarian cancers have been identified.

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