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


METHODS
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.


CONCLUSIONS
VEGF-C expression is closely related to invasive phenotype and affects the patient's survival in ovarian carcinomas.
Ueda
Masatsugu
M
Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan. gyn017@poh.osaka-med.ac.jp
Hung
Yao-Ching
YC
Terai
Yoshito
Y
Kanda
Koji
K
Kanemura
Masanori
M
Futakuchi
Hikari
H
Yamaguchi
Hiroyuki
H
Akise
Daisuke
D
Yasuda
Masayuki
M
Ueki
Minoru
M
D000906:Antibodies / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D018952:Antigens, CD34; D042582:Vascular Endothelial Growth Factor C; D020778:Matrix Metalloproteinase 2