The Relationship Of Vascular Growth Factor And Micro Vascular Density With Prognosis Of Colorectal Carcinoma

Objective: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) in colorectal cancer, and their relationship with clinicopathological and prognosis significance in colorectal cancer.Method: From 1995.12 to 1999.10, the General Surgery of Juxian Traditional Chinese Medical (TCM) Hospital in Shandong Province participated in the nationwide cooperative study, which concentrated in protesting liver metastasis by means of colorectal carcinoma portal vein catheterizational 5-FU chemotherapy. Eighty cases of colorectal carcinoma patients were surgically treated. Using PV-9000 immunohistochemical method, the expression of VEGF and MVD were examined in 80 cases of carcinoma, 25 cases of paratumor tissue, and 25 cases of normal colorectal tissue.Results: No positive immunoreactive staining was obtained in normal colorectal tissue and blank and control samples VEGF staining, which is even brown yellow granules, can be seen in cytoplasmanal membrane of tumor cells, with positive expression in little paratumor epithelium and its nevghborring vascular endothelial cells. VEGF positive tumor cells distributed unevenly, with invasion area of tumorcells stained deeper. Among 80 cases of colorectal cancer, 53 were positive for VEGF immunohistochemical staining (66.25 %). Among 25 cases of paracolorectal mucal tissue, 4 were positive for VEGF immunohistochemical staining (16%), There was a significant difference in the positive expression of VEGF between colorectal cancer tissue and paracolorectal mucal tissue(P<0.01). The expression of VEGFin colorectal cancer tissue was significantly higher than normal colorectal tissue and paracolorectal cancer tissue(P<0.05) ,but there was no difference between normal and paracolorectal cancer tissue(P > 0.05). The microvascular density(MVD) ranged from 6 to 39, averaged 19.23±1.11, with a median of 27. MVD had no relationship with colorectal cancer histotype and the degree of differentiation(P>0.05), but had close relationship with invasion depth(P<0.05). And the deepen the invasion was, the higher the MVD was. The expression rate of MVD in Dukes C stage was higher than A+B stage. MVD was significantly higher in patients with lymph node metastasis than patients without lymph node metastasis (29.88±5.64 vs 13.85±7.38, P<0.05). MVD was significantly higher in patients with positive VEGF expression than patients with negative VEGF expression (21.82±6.24 vs 9.57±3.68, P<0.05). There was a significant positive correlation between VEGF expression and MVD (r=0.767,P < 0.01).Five year survival rate of colorectal cancer decrease gradually with the strength of the VEGF expression, survival rate in negative VEGF expression was higher than positive VEGF expression, in comparison with weak, middle and strong positive expression, respectively , had statistive significance (P<0.01). The survival time shortened with the increase of MVD in colorectal carcinoma patients, and there was a significant negative correlation between MVD and the survival time of colorectal carcinoma (r=-0.790, P < 0.01).By Cox proportion hazards regression model analysis, VEGF.MVD and Dukes stage were main risk factors. Among these, the MVD had the closest correlation with 5 year survival rate of colorectal cancer patients, and it was the most important risk factor (P=0.000), the relative risk coeffient was 1.158. Among 53 cases of positive VEGF expression, 28 cases accepted portal vein catheterizational 5-FU chemotherapy after operation, 15 cases did not. 5-FU portal vein catheterizational chemotherapy can improve 5 year survival rate incases with positive VEGF expression (72.35% vs 21.27%).Conclusion: VEGF or MVD ,as detectable marker, can help the diagnosis of colorectal carcinoma and be an objective index for prognosis. The angiogenesis of tumor can be inhibited by interfering the expression and action process of VEGF, or destroying its receptors, the growth and metastasis of colorectal carcinoma were inhibited, which were essential for improving the prognosis of the tumor. For cases with positive VEGF expression, 5-FU resulted in good improvement in 5 year survival rate.