Abstract | OBJECTIVE: The purpose of this study was to identify genes that are highly differentially expressed in metastatic serous papillary ovarian tumors (MET) when compared with primary ovarian serous carcinomas ( OSPC). STUDY DESIGN: An oligonucleotide microarray with probe sets complementary to >14,500 human genes was used to determine whether patterns of gene expression may differentiate OSPC from MET in 31 snap-frozen serous papillary ovarian carcinomas (ie, 14 primary OSPC and 17 omental metastasis [MET]). RESULTS: Hierarchic cluster analysis of gene expression in OSPC and MET identified 156 genes that exhibited > 2-fold differences (P < .05) and that distinguished OSPC from MET. A number of invasion and metastasis predictive genes (including plasminogen activator; matrix metalloproteinase; matrix structural constituent genes encoding products with collagen, heparin, and hyaluronic acid binding activity; genes encoding receptors for insulin-like growth factors; vascular endothelial growth factor; endothelin type A; fibroblast growth factor; thrombospondin 1 and 2; type A and B integrins, and chemokines [ stromal cell-derived factor 1 (CXCL12)]) were found among the 120 genes that were highly differentially overexpressed in MET, when compared with OSPC. Down-regulated genes in MET compared with OSPC included hepsin and testisin. Overexpression of CXCL12, matrix metalloproteinase, plasminogen activator, type A and B integrins, and hepsin genes was validated by quantitative real-time polymerase chain reaction in all samples. Finally, overexpression of CXCL12 in MET, when compared with OSPC, was validated at the protein level by immunohistochemistry. CONCLUSION: Gene expression profiling may differentiate metastatic ovarian cancer from primary OSPC. The identification of metastasis-associated genes may provide a foundation for the development of new type-specific diagnostic strategies and treatment for metastatic ovarian cancer.
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Authors | Eliana Bignotti, Renata A Tassi, Stefano Calza, Antonella Ravaggi, Elisabetta Bandiera, Elisa Rossi, Carla Donzelli, Brunella Pasinetti, Sergio Pecorelli, Alessandro D Santin |
Journal | American journal of obstetrics and gynecology
(Am J Obstet Gynecol)
Vol. 196
Issue 3
Pg. 245.e1-11
(Mar 2007)
ISSN: 1097-6868 [Electronic] United States |
PMID | 17346539
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Cystadenocarcinoma, Serous
(genetics, secondary)
- Female
- Gene Expression Profiling
- Humans
- Middle Aged
- Neoplasm Metastasis
(genetics)
- Ovarian Neoplasms
(genetics, pathology)
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