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Vascular Endothelial Growth Factor-C Expression and Invasive Phenotype in Ovarian Carcinomas

Authors' Affiliations: ¹ Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan and ² Department of Obstetrics and Gynecology, China Medical College, Taichung, Taiwan, Republic of China

Requests for reprints: Masatsugu Ueda, Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan. Phone: 81-72-683-1221; Fax: 81-72-681-3723; E-mail: gyn017{at}poh.osaka-med.ac.jp

Purpose: To investigate the biological correlation between vascular endothelial growth factor (VEGF)-C expression and invasive phenotype in ovarian carcinomas.

Experimental Design: Gene and protein expression levels of VEGF-C in 10 ovarian carcinoma cell lines were correlated with invasive activity of the cells. The correlation between immunohistochemical expression of VEGF-C and tumor aggressiveness in 73 ovarian carcinomas was also examined with respect to clinicopathologic features and patient outcome.

Results: VEGF-C gene and protein expression differed remarkably among the cell lines, and there was a statistical correlation among VEGF-C expression, in vitro invasive activity, and matrix metalloproteinase-2 (MMP-2) gene expression and its activity. Anti-VEGF-C and anti-MMP-2 antibodies inhibited the invasive activity of tumor cells. VEGF-C expression in clinical tissue samples was well correlated with clinical stages, retroperitoneal lymph node metastasis, MMP-2 expression, angiogenesis, lymphangiogenesis, and low apoptotic index (AI). The patients whose tumors had strong VEGF-C expression and low AI underwent a poorer prognosis than did those with weak VEGF-C expression and high AI.

Conclusion: VEGF-C expression is closely related to invasive phenotype and affects the patient's survival in ovarian carcinomas.

Key Words: VEGF-C • MMP • Angiogenesis • Apoptosis • Ovarian carcinoma

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