Distribution and Clinical Significance of Heparan Sulfate Proteoglycans in Ovarian Cancer

Abstract

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.

Immunohistochemical characteristics of cystic odontogenic lesions: a comparative study

“…CD138 is normally expressed in the epithelial cells and some mesenchymal cells such as plasma cells and immature B lymphocytes. However, it has been demonstrated that CD138 is expressed by the stromal cells in the some neoplastic and non-neoplastic odontogenic lesions (ameloblastoma, KCOT and DC), and ovarian cancers, as well as plasma cells (24,33). It has also been stated that the expression of CD138 is associated with poor prognosis (24, 33).…”

“…However, it has been demonstrated that CD138 is expressed by the stromal cells in the some neoplastic and non-neoplastic odontogenic lesions (ameloblastoma, KCOT and DC), and ovarian cancers, as well as plasma cells (24,33). It has also been stated that the expression of CD138 is associated with poor prognosis (24,33). CD138 (syndecan 1) shifting from epithelium to stroma was reported in invasive non-odontogenic solid tumors including breast, prostate, lung, and colon cancers (21).…”

Superficial spreading squamous cell carcinoma of the uterine cervix involving the endometrium: Report of two cases with emphasis on the likely molecular mechanism

“…A correlation between CD138 expression and carcinogenesis has been investigated in various organs. Increased expression of CD138 has been reported in endometrial and ovarian carcinomas (6,7). By contrast, decreased expression of CD138 has been reported to correlate with tumor invasion and progression of cervical cancer (8-10).…”

Toward an Integrative Analysis of the Tumor Microenvironment in Ovarian Epithelial Carcinoma

“…HB-EGF contains a heparan sulfate binding motif that enables its binding to heparan sulfate proteoglycans (HSPG) in the coelomic epithelium. An analysis of HSPG expression in normal OSE compared to that derived from tumors evinced normal patterns for all cell surface PGs except syndecan-1 (SDC1), which was highly expressed in tumor cells but absent from normal epithelium [80]. In addition, only SDC1 and glypican-1 were associated with poor prognoses in univariate analysis.…”