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Abstract
BackgroundWhile numerous studies have characterized primary ovarian tumors, little information is available regarding expression patterns of metastatic sites of this cancer. To define sets of genes that distinguish primary and metastatic ovarian tumors, we used cDNA microarrays to characterize global gene expression patterns in 38 effusions (28 peritoneal, 10 pleural) and 8 corresponding primary ovarian tumors, and searched for associations between expression patterns and clinical parameters.ResultsWe observed multidimensional variation in expression patterns among the cancers. Coordinate variation in expression of genes from two chromosomal regions, 8q and 19q, was seen in subsets of the cancers indicating possible amplifications in these regions. A set of 112 unique genes of known function was differentially expressed between primary tumors and effusions using supervised analysis. Relatively few differences were seen between effusions isolated from the pleural and peritoneal cavities or between effusions from patients diagnosed with stage III and stage IV cancers. A set of 84 unique genes was identified that distinguished high from lower grade ovarian cancers. The results were corroborated using immunocytochemistry, mRNA in situ hybridization, and immunoblotting.ConclusionThe extensive variation in expression patterns observed underscores the molecular heterogeneity of ovarian cancer, but suggests a similar molecular profile for ovarian carcinoma cells in serosal cavities.
Highlights
While numerous studies have characterized primary ovarian tumors, little information is available regarding expression patterns of metastatic sites of this cancer
The clustering analyses divided the ovarian cancer specimens into two major groups, with 4 of the 8 primary tumors clustering together but apart from their paired effusions
Some of the cancers were notable for the elevated expression of a cluster of genes residing on chromosome segment 8q21-24 and the coordinate variation in expression of these genes suggests that there may be an amplification of this region of chromosome 8 in some of the ovarian cancers
Summary
While numerous studies have characterized primary ovarian tumors, little information is available regarding expression patterns of metastatic sites of this cancer. A number of metastasis-associated molecules have been reported to be differentially expressed between primary ovarian tumors and tumor cells in effusions [3,4,5,6,7,8,9,10,11,12], but little is known regarding the mechanism of metastases. Molecular characterization of ovarian carcinoma using DNA microarrays has so far focused on primary tumors [13,14,15,16,17,18,19,20,21,22]. The paucity of data regarding the biological characteristics of ovarian carcinoma cells in effusions at both the phenotypic and genotypic level limits our understanding of tumor progression in this disease. Molecular analysis of malignant effusions might contribute to better predictions of survival and treatment response
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