Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Cancer Research UK and University of Manchester Department of Medical Oncology, Paterson Institute for Cancer Research, Manchester, England.
E June
EJ
Davies
Fiona H
FH
Blackhall
Jonathan H
JH
Shanks
Guido
G
David
Alan T
AT
McGown
Ric
R
Swindell
Richard J
RJ
Slade
Pierre
P
Martin-Hirsch
John T
JT
Gallagher
Gordon C
GC
Jayson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011509:Proteoglycans / Q000096:biosynthesis; D053668:Syndecan-1; D053669:Syndecan-2; D053670:Syndecan-3; D053671:Syndecan-4; D053667:Syndecans; D013997:Time Factors; D016896:Treatment Outcome
D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; C508245:SDC2 protein, human; C508301:SDC3 protein, human; C508304:SDC4 protein, human; D053668:Syndecan-1; D053670:Syndecan-3; D053671:Syndecan-4; D053667:Syndecans; C071927:perlecan; D053669:Syndecan-2