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Clinical Research 15: Clinical Research 5: Genitourinary Malignancy

Abstract #4507

Global gene expression profiling of mucinous ovarian tumors and cystadenomas identifies genes of clinicopathologic importance

NCI, NIH, Bethesda, MD, Brigham and Women’s Hospital, Boston, MA, Harvard School of Public Health, Boston, MA

The poor prognosis of patients with mucinous ovarian cancer remains a challenge to gynecologic oncologists, as these patients often present with aggressive chemo-resistant disease. In order to understand the molecular mechanisms contributing to the clinicopathological characteristics of mucinous ovarian carcinoma, we carried out gene expression profiling of 19 microdissected tumors (10 LMP and 9 adenocarcinoma), as well as 6 microdissected mucinous cystadenomas, using Affymetrix U133 Plus 2.0 oligonucleotide microarrays. Hierarchical clustering and binary tree prediction analysis were used to determine the relationships among normal ovarian surface epithelium, mucinous specimens, and a series of previously profiled microdissected serous tumors. PathwayAssist software was used to identify putative signaling pathways involved in the development of mucinous ovarian tumors (both LMP and adenocarcinomas). A comparison of the gene profiles between mucinous tumors and normal ovarian epithelium identified 2916 and 1765 differentially expressed in genes (p-value <0.001 with a 95% probability of identifying less than 10% false discoveries) in LMP and grade 1 and 2 adenocarcinomas, respectively. Hierarchical clustering revealed a close association between the mucinous tumors and serous adenocarcinomas, with the mucinous LMP tumors grouping independently of the serous LMP specimens. Binary tree analysis confirmed the clustering relationships for the mucinous tumors as compared to their serous counterparts. Furthermore, mucinous cystadenoma expression profiles were similar to mucinous LMP and adenocarcinomas specimens. PathwayAssist analysis identified co-regulated genes involved in drug resistance in both mucinous LMP tumors and adenocarcinomas. In addition, genes involved in cytoskeletal regulation were specifically up regulated in the mucinous adenocarcinomas. Our findings resolve the relationships among mucinous and serous tumors, and identify clinicopathologic features defining mucinous ovarian tumors