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Distribution and Clinical Significance of Heparan Sulfate Proteoglycans in Ovarian Cancer

¹ Cancer Research UK and University of Manchester Department of Medical Oncology, Paterson Institute for Cancer Research, Manchester, England;
² Department of Histopathology, Christie Hospital NHS Trust, Manchester, England;
³ Department of Medicine, University of Leuven, Leuven, Belgium.;
⁴ Cancer Research UK Department of Experimental Pharmacology, Paterson Institute for Cancer Research, Manchester, England;
⁵ Department of Medical Statistics, Christie Hospital NHS Trust, Manchester, England;
⁶ Department of Obstetrics and Gynaecology, Hope Hospital, Salford, Manchester, England;
⁷ Department of Gynaecological Oncology, St. Mary’s Hospital, Oxford Road, Manchester, England

Purpose: Heparan sulfate proteoglycans have been implicated in cancer cell growth, invasion, metastasis, and angiogenesis. This study was designed to compare their expression in normal ovary and ovarian tumors and then to examine their prognostic significance in ovarian cancer.

Experimental Design: The expression of syndecan-1, -2, -3, and -4, glypican-1, and perlecan was assessed by immunohistochemistry in 147 biopsies that included normal ovary and benign, borderline, and malignant ovarian tumors. Clinical data, including tumor stage, performance status, treatment, and survival, were collected. Univariate and multivariate analyses were performed to evaluate prognostic significance.

Results: The expression patterns of syndecan-1 and perlecan were altered in ovarian tumors compared with normal ovary. Syndecan-1 was not detected in normal ovary but was present in the epithelial and stromal cells of benign and borderline tumors and in ovarian adenocarcinomas. Perlecan expression was decreased in basement membranes that were disrupted by cancer cells but maintained in the basement membranes of blood vessels. Syndecan-2, -3, and -4, and glypican-1 were expressed in normal ovary and benign and malignant ovarian tumors. Stromal expression of syndecan-1 and glypican-1 were poor prognostic factors for survival in univariate analysis.

Conclusion: We report for the first time distinct patterns of expression of cell surface and extracellular matrix heparan sulfate proteoglycans in normal ovary compared with ovarian tumors. These data reinforce the role of the tumor stroma in ovarian adenocarcinoma and suggest that stromal induction of syndecan-1 contributes to the pathogenesis of this malignancy.

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