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Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer
Affiliations: 1 Walter Reed Army Medical Center, Washington, DC; 2 Laboratory of Biosystems and Cancer, National Cancer Institute, Bethesda, Maryland; and 3 Department of Obstetrics and Gynecology/Division of Gynecologic Oncology, Duke University, Durham, North Carolina Clinical Cancer Research Vol. 11, 4056-4066, June 1, 2005 Requests for reprints: G. Larry Maxwell, Division of Gynecologic Oncology, Walter Reed Army Medical Center, 6900 Georgia Avenue, Washington, DC 20307. Phone: 202-782-8512; Fax: 202-782-9278; E-mail: George Maxwell Abstract Previous studies using cDNA microarray have indicated that distinct gene expression profiles characterize endometrioid and papillary serous carcinomas of the endometrium. Molecular studies have observed that mixed mullerian tumors, characterized by both carcinomatous and sarcomatous components, share features that are characteristic of endometrial carcinomas. The objective of this analysis was to more precisely define gene expression patterns that distinguish endometrioid and papillary serous histologies of endometrial carcinoma and mixed mullerian tumors of the uterus. One hundred nineteen pathologically confirmed uterine cancer samples were studied (66 endometrioid, 24 papillary serous, and 29 mixed mullerian tumors). Gene expressions were analyzed using the Affymetrix Human Genome Arrays U133A and U133B Genechip set. Unsupervised analysis revealed distinct global gene expression patterns of endometrioid, papillary serous, mixed mullerian tumors, and normal tissues as grossly separated clusters. Two-sample t tests comparing endometrioid and papillary serous, endometrioid and mixed mullerian tumor, and papillary serous and mixed mullerian tumor pairs identified 1,055, 5,212, and 1,208 differentially expressed genes at P < 0.001, respectively. These data revealed that distinct patterns of gene expression characterize various histologic types of uterine cancer. Gene expression profiles for select genes were confirmed using quantitative PCR. An understanding of the molecular heterogeneity of various histologic types of endometrial cancer has the potential to lead to better individualization of treatment in the future. Complete cross-referenced lists of differentially expressed genes E EASE MMT EASE PS EASE Posted Class Comparison E vs MMT Posted Class Comparison E vs PS Posted Class Comparison MMT vs PS Posted Cross Referenced Gene Lists |