Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer.
OBJECTIVE
Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular protein that modulates cell adhesion and growth. It is thought to play a decisive role in tissue remodeling and angiogenesis. Alterations in SPARC expression have been observed in a variety of solid tumors; however, no consistent pattern of deregulation has been characterized. Vascular endothelial growth factor (VEGF) has emerged as an important regulator of tumor neovascularization. Recent work has shown that SPARC modulates the mitogenic activity of VEGF in normal endothelium. While its role in malignant transformation remains elusive, SPARC may contribute to tumor propagation and invasion. This study examines the immunoreactivity of SPARC and VEGF associated with neoplastic transformation of the ovary.


METHODS
Immunostaining for VEGF and SPARC protein was performed on 62 archival specimens.


RESULTS
Fourteen normal ovaries and 48 ovarian carcinomas were evaluated. SPARC was detected in the stroma of 63% of ovarian carcinomas. In contrast, SPARC was observed in the stroma of only 29% of normal ovaries (P = 0.02). Furthermore, SPARC was limited in normal ovaries to premenopausal patients, juxtaposed either with vesiculated follicles or within the corpus luteum. VEGF was observed in 42% of ovarian carcinomas with immunoreactivity confined to tumor cells. The level of VEGF immunoreactivity was significantly higher in ovarian carcinoma compared to normal ovary epithelium (42 vs 7%, P = 0.02).


CONCLUSIONS
Immunoreactivity of SPARC and VEGF is heightened in association with ovarian carcinoma, with a distinct distribution of SPARC in the stroma of neoplastic ovaries and VEGF within tumor cells. No obvious pattern of coincident SPARC and VEGF immunoreactivity was detected. These results indicate the possibility of an aberration in the interaction that has been described in normal endothelium between SPARC and VEGF in association with malignant transformation.
Paley
P J
PJ
The Division of Gynecologic Oncology, University of Washington, Seattle, Washington 98195, USA.
Goff
B A
BA
Gown
A M
AM
Greer
B E
BE
Sage
E H
EH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000276:immunology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015676:Osteonectin / Q000096:biosynthesis* / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013737:Testis / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D015676:Osteonectin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors