The Expression Of VEGF-C And Its Receptor VEGFR-3 In Stomach Cancer And Its Relationship With Tumor Infiltration,Metastasis And Prognosis

Objective: To evaluate the expression of VEGF-C and its receptor VEGFR-3 in stomach cancer and its relationship with tumor infiltration, metastasis and prognosisMethods: The specimens were taken from 80 patients with, primary gastric cancer in An Hui Medical Afflicated Hospital from January 1995 to June 1998. All cases were follow-up for five years. Among them, the ration of sex man and woman was 61:19; the age varied from 28 to 77 years old and the median age was 59 ; 29 cases had lymph node metastasis and 51 without ; 61 cases infiltrated into muscle and serosa and 19 cases infiltrated into mucosa and submucosa ; 31 cases were the middle and well differtiated adenocarcinoma and 49 cases were low- and undiffertiated; 36 cases were infiltrated and ulcerated growth and 44 cases were not; 38 cases tumor diameter were beyond 3cm and 42 below; 27 cases were located cardiac and upper part, 25 and 28 were located middle and low part. The radical operations were taken to all cases and R2 lymphadenectomy were mainly used. Additional, 20 specimens biopsied from superficial gastritis were used as control. Using SP immunohistochemistry, we studied the expression of VEGF-C and its receptor VEGFR-3 in stomach cancer and its relationship with tumor infiltration metastasis and prognosis . SPSS 11.5 was used to analyze the results.Results: 1. the expression of VEGF-C in gastric carcinoma was significantly higher than that in control (63.75% vs 30.0%, P<0.01), Immunohistological staining with VEGF-C specific polyclonal antibody showed cytoplasmic and membranous stainingin the cancer cells.2. The positive expression of VEGFR-3 is chiefly located in cytomembrane and cytoplasm of cancer cells and vessel endothelial cells. The VEGFR-3 positive vessels were mainly seen in tumor periphery, especially in the frontier of cancer cell penetration. Those vessels have large lumen, thin wall and irregular shape; furthermore, some cancer cells are involved in VEGFR-3 positive vessels.3. By spearman correlation analysis, we found that in cancer cells, VEGF-C expression correlated with VEGFR-3 expression(r=0.421, P<0.05). By T test, we found that the number of VEGFR-3 positive vessels in VEGF-C positive group was higher than that in VEGF-C negative group (18.09+7.66 vs 13.62+6.93, P<0.05);4. The positive expression of VEGF-C in cases that penetrate into muscle and serosa is significantly higher than that into mucosa and submucosa group (72.13% vs 36.84%, P<0.05); the positive expression of VEGF-C in lymph node metastasis group is higher than that in no lymph node metastasis group (89.29% vs 50.0%, P<0.05); The expression of VEGFR-3 in cancer cell is associated with tumor size, infiltration depth and lymph node metastasis. The number of VEGFR-3 positive vessel is associated with tumor size, infiltration depth and lymph node metastasis.5. By logistic regression analysis, we found that tumor growth pattern. VEGF-C expression and the number of VEGFR-3 vessel are independent factors that influence lymph node metastasis.6. By Kaplan-Meier survival analysis and Cox regression model analysis, VEGF-C expression and infiltration depth are found to be independent factors for patients' prognosis.Conclusion: 1. VEGF-C is expressed in stomach cancer and its overexpressioncorrelates with gastric cancer infiltration and lymph node metastasis.2 .VEGFR-3 is expressed in stomach cancer and its overexpression correlates withtumor size infiltration and lymph node metastasis. VEGFR-3 is also expressed in vascular endothelial cell. The number of VEGFR-3 possive vessel is correlated with tumor size infiltration and lymph node metastasis.3. It is likely that VEGF-C can act with VEGFR-3 via para- and self-secreted pattern. Via self-secreted pattern ,VEGF-C might improve tumor cell invasive ability ; via para-secreted, VEGF-C might induce lymphatic cell proliferation and lymphangiogenesis.4. The tumor growth pattern VEGF-C and VEGFR-3 possive vessel are found to be independent factors for local lymph node metasta...