Correlation between vascular endothelial growth factor-C expression and invasion phenotype in cervical carcinomas.
The correlation between vascular endothelial growth factor (VEGF)-C gene expression and in vitro invasive activity and matrix metalloproteinase (MMP)-2 or 9 gene expression and proteolytic activity in 11 cervical carcinoma cell lines, was investigated. Immunohistochemical expression of VEGF-C in 52 cervical carcinoma tissues was also correlated with tumor aggressiveness with respect to clinicopathologic features, tumor vascularity, MMP-2 expression and patient outcome. Expression of VEGF-C mRNA differed remarkably among the cell lines and there was a statistical correlation between VEGF-C gene expression and the number of invaded tumor cells (p = 0.0009) and MMP-2 gene expression and activity (p < 0.05). Anti-VEGF-C antibody inhibited the invasive and proteolytic activity of tumor cells in a concentration-dependent manner. VEGF-C or MMP-2 expression in clinical tissue samples was well correlated with depth of myometrial invasion, endometrial invasion, pelvic lymphnode metastasis and tumor vascularity (p < 0.05) and there was a close relation between VEGF-C and MMP-2 expression (p < 0.0001) in cervical carcinomas. Overall survival rates for 14 patients with strong VEGF-C staining tumors were lower than those for 38 patients with weak VEGF-C staining tumors (p = 0.0132) and VEGF-C tissue status emerged as an independent prognostic parameter (p = 0.0232). These results suggest that VEGF-C expression is closely related to invasion phenotype and affects the patient's survival in cervical carcinomas.
Ueda
Masatsugu
M
Department of Obstetrics and Gynecology, Osaka Medical College, Takasuki, Osaka, Japan. gyn017@poh.osaka-med.ac.jp
Terai
Yoshito
Y
Yamashita
Yoshiki
Y
Kumagai
Koji
K
Ueki
Ken
K
Yamaguchi
Hiroyuki
H
Akise
Daisuke
D
Hung
Yao-Ching
YC
Ueki
Minoru
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C
D017931:DNA Primers; D004273:DNA, Neoplasm; D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9