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Published on: May 20, 2014
Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer
P J Paley1, B A Goff, A M Gown
1The Division of Gynecologic Oncology, University of Washington, Seattle, Washington 98195, USA.
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.
Insights
Secreted protein, acidic and rich in cysteine (SPARC) and vascular endothelial growth factor (VEGF) show heightened immunoreactivity in ovarian carcinoma. SPARC is found in the stroma, while VEGF is within tumor cells, suggesting altered interactions in cancer.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Secreted protein, acidic and rich in cysteine (SPARC) is a matricellular protein involved in cell adhesion, growth, tissue remodeling, and angiogenesis.
- Vascular endothelial growth factor (VEGF) is a key regulator of tumor neovascularization.
- SPARC modulates VEGF activity in normal endothelium, but its role in ovarian cancer is not well understood.
Purpose of the Study:
- To investigate the expression and distribution of SPARC and VEGF in normal ovaries and ovarian carcinomas.
- To explore potential alterations in the SPARC-VEGF interaction during ovarian neoplastic transformation.
Main Methods:
- Immunostaining was performed on 62 archival specimens, including 14 normal ovaries and 48 ovarian carcinomas.
- Expression levels and cellular localization of SPARC and VEGF were assessed.
Main Results:
- SPARC was detected in the stroma of 63% of ovarian carcinomas, compared to 29% of normal ovaries (P = 0.02).
- VEGF was observed in 42% of ovarian carcinomas, primarily within tumor cells, with significantly higher immunoreactivity than in normal ovarian epithelium (42% vs 7%, P = 0.02).
- SPARC in normal ovaries was localized to the stroma, associated with follicles or the corpus luteum, and primarily in premenopausal patients.
Conclusions:
- Both SPARC and VEGF immunoreactivity are increased in ovarian carcinoma.
- SPARC is predominantly stromal in neoplastic ovaries, while VEGF is localized to tumor cells.
- The distinct distribution suggests a potential aberration in the SPARC-VEGF interaction in ovarian cancer compared to normal endothelium.
