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Overexpression of the Cell Adhesion Molecules DDR1, Claudin 3, and Ep-CAM in Metaplastic Ovarian Epithelium and Ovarian Cancer
Purpose: A better understanding of the molecular pathways underlying the development of epithelial ovarian cancer (EOC) is critical to identify ovarian tumor markers for use in diagnostic or therapeutic applications. The aims of this study were to integrate the results from 14 transcript profiling s...
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Published in: | Clinical cancer research 2004-07, Vol.10 (13), p.4427-4436 |
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Main Authors: | , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose: A better understanding of the molecular pathways underlying the development of epithelial ovarian cancer (EOC) is critical
to identify ovarian tumor markers for use in diagnostic or therapeutic applications. The aims of this study were to integrate
the results from 14 transcript profiling studies of EOC to identify novel biomarkers and to examine their expression in early
and late stages of the disease.
Experimental Design: A database incorporating genes identified as being highly up-regulated in each study was constructed. Candidate tumor markers
were selected from genes that overlapped between studies and by evidence of surface membrane or secreted expression. The expression
patterns of three integral membrane proteins, discoidin domain receptor 1 (DDR1), claudin 3 (CLDN3), and epithelial cell adhesion
molecule, all of which are involved in cell adhesion, were evaluated in a cohort of 158 primary EOC using immunohistochemistry.
Results: We confirmed that these genes are highly overexpressed in all histological subtypes of EOC compared with normal ovarian surface
epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC. Furthermore, we determined that these genes are also expressed
in ovarian epithelial inclusion cysts, a site of metaplastic changes within the normal ovary, in borderline tumors and in
low-grade and stage cancer. A trend toward an association between low CLDN3 expression and poor patient outcome was also observed.
Conclusions: These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development
of EOC and have potential application in the early detection of disease. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-04-0073 |