The Study On Relationship Between The Expression Of Vascular Endothelial Growth Factor And Invasion And Metastasis In Ovarian Carcinoma

The Study On Relationship Between The Expression Of Vascular Endothelial Growth Factor And Invasion And Metastasis In Ovarian CarcinomaBackground: Ovarian cancer is the most lethal of gynecological malignancies, and the seventh most common cancer in women worldwide, after breast, cervix, colon/rectum, stomach, corpus uteri, and lung cancers. Each year, an estimated 26,000 women in the United States and 5,000 women in the UK are diagnosed with ovarian cancer. During any given year, approximately 14,500 cases in the United States and 4,200 cases in the UK die from this disease. In the United States, ovarian cancer is the fourth leading cause of solid tumor cancer deaths among women. In the UK, it is the fifth commonest cause of cancer death in women. Approximately 1 woman in 70 will develop ovarian cancer, and 1 women in 100 will die from it. In China, the mortality rate of ovarian cancer was 0.67/100,000 per year during 1990's, and is the sixth commonest cause of cancer death in Chinese women. This high mortality rate is due to presentation at an advanced stage of the disease as symptoms of the disease are insidious in onset and non-specific in nature. Over 75% of women with the ovarian cancer have tumor spread beyond the pelvis at the time of diagnosis and it is reason why overall five-year survival rate is very poor; about only 25% to 30%. The common pathway of tumor progression in ovarian carcinomas is peritoneal dissemination. The progressive accumulation of ascites is also frequent with or without malignant tumor cells in the peritoneal fluid. Tumor angiogenesis is considered essential for tumor growth and the development of metastases. Vascular Endothelial Growth Factor (VEGF) is considered to play a key role in tumor angiogenesis. VEGF, a highly specific mitogen for vascular endothelial cells and a vascular permeability factor, is produced in elevated amounts by many tumors, including ovarian carcinomas. The known human receptors for VEGF, Flt-1 and KDR/flk-1 are both cell surface tyrosine kinases and are expressed on endothelial cells. Acting through these receptors, VEGF may stimulate angiogenesis and promote tumor progression. Purpose: To detect the role of VEGF in ovarian tumor growth, invasion andmetastasis, and to analyze the relationship between the expression of VEGF and histopathologic parameters and overall survive in ovarian cancer: to determine the diagnostic value of preoperative serum VEGF in patients with ovarian neoplasms; to detect the role of VEGF gene in angiogenesis, invasion and metastasis of ovarian carcinoma: to evaluated the effects of anti-VEGF antibody on the growth of SKOV3 in vitro. Methods: Tumor samples from 54 patients with ovarian carcinomas, 16 cases of benign tumor and 20 cases of normal controls were evaluated for VEGF mRNA and its subtypes expression by reverse-transcriptase polymerase chain reaction using acrylamide gel and sliver staining: meanwhile we detected VEGF and its receptors flt-1 -, KDR/flk-1 protein expression by IHC, and an antibody to von willebrand factor (F8) was also used to detect tumor microvessel count determinations; plasmid DNA of VEGF gene was introduced into ovarian cancer cell line OVCAR3 by Lipofectin. VEGF expression of derived clone cells transfected with VEGF gene was identificated by using Northern-blot and Western-blot, and the effect of VEGF gene on the growth of OVCAR3 in vitro and on the tumor invasion and angiogenesis of nude mice in vivo were also investigate by MTT and xenograft study. In addition, we determined VEGF serum levels in patients with ovarian neoplasms (105 ovarian carcinomas, 25 benign tumors) and 90 healthy women as controls by ELISA, also studied the change of serum VEGF levels in preoperative and postoperative of ten cases. Results: Firstly, the expression of VEGF . mRNA and its subtypes VEGF 121 ,VEGF 165 were significantly higher than that in benign tumor and normal control; VEGF 189 were only expressed in ovarian carcinomas. The levels of VEGF, VEGF receptors (Flt-1 and KDR/Flk-1) in ovarian carcinomas wer...