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Expression Profiling of Mucinous Tumors of the Ovary Identifies Genes of Clinicopathologic Importance

Authors' Affiliations: ¹ Cell and Cancer Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland; ² Laboratory of Gynecological Oncology and ³ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School; and ⁴ Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts

Requests for reprints: Michael J. Birrer, Cell and Cancer Biology Branch, National Cancer Institute, NIH, Room 1130, Building 37, 9000 Rockville Pike, Bethesda, MD 20892. Phone: 301-402-9586; Fax: 301-480-4756; E-mail: birrerm{at}mail.nih.gov.

Purpose: To elucidate the molecular mechanisms contributing to the unique clinicopathologic characteristics of mucinous ovarian carcinoma, global gene expression profiling of mucinous ovarian tumors was carried out.

Experimental Design: Gene expression profiling was completed for 25 microdissected mucinous tumors [6 cystadenomas, 10 low malignant potential (LMP) tumors, and 9 adenocarcinomas] using Affymetrix U133 Plus 2.0 oligonucleotide microarrays. Hierarchical clustering and binary tree prediction analysis were used to determine the relationships among mucinous specimens and a series of previously profiled microdissected serous tumors and normal ovarian surface epithelium. PathwayAssist software was used to identify putative signaling pathways involved in the development of mucinous LMP tumors and adenocarcinomas.

Results: Comparison of the gene profiles between mucinous tumors and normal ovarian epithelial cells identified 1,599, 2,916, and 1,765 differentially expressed in genes in the cystadenomas, LMP tumors, and adenocarcinomas, respectively. Hierarchical clustering showed that mucinous and serous LMP tumors are distinct. In addition, there was a close association of mucinous LMP tumors and adenocarcinomas with serous adenocarcinomas. Binary tree prediction revealed increased heterogeneity among mucinous tumors compared with their serous counterparts. Furthermore, the cystadenomas coexpressed a subset of genes that were differentially regulated in LMP and adenocarcinoma specimens compared with normal ovarian surface epithelium. PathwayAssist highlighted pathways with expression of genes involved in drug resistance in both LMP and adenocarcinoma samples. In addition, genes involved in cytoskeletal regulation were specifically up-regulated in the mucinous adenocarcinomas.

Conclusions: These data provide a useful basis for understanding the molecular events leading to the development and progression of mucinous ovarian cancer.

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