Relationship between the expression of iNOS,VEGF,tumor angiogenesis and gastric cancer

Abstract

Aim: To investigate the relationship between the expression of inducible nitric oxide synthase(iNOS),vascular endothelial growth factor(VEGF),the microvascular density (MVD) and the pathological features and clinical staging of gastric cancer.

Methods: Immunohistochemical staining was used for detecting the expression of iNOS and VEGF in 46 resected specimens of gastric carcinoma; the monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and MVD was detected by counting of CD34-positive vascular endothelial cells.

Results: Of 46 resected specimens of gastric carcinoma,the rates of expressions of iNOS and VEGF were 58.70% and 76.09%, respectively,and MVD averaged 55.59+/-19.39.Judged by the standard TNM criteria, the rate of expression of iNOS in stage IV (84.46%) was higher than those in stage I,II, III(Fish exact probabilities test, P=0.019,0.023 and 0.033,respectively);the rates of expression of VEGF in stage III,IV (76.0%,92.31%,respectively) were higher than those in stage I,II (Fish exact probabilities test, P=0.031,0.017,0.022 and 0.019). MVDs in stage III,IV(64.72+/-14.96,67.09+/-18.29,respectively) were higher than those in stage I,II(t=2.378,4.015,2.503 and 2.450, P<0.05,P<0.001,P<0.001, P<0.05,respectively). In 37 gastric carcinoma specimens with lymph node metastasis, MVD(68.69+/-18.07) and the rates of expression of iNOS and VEGF(70.27%,83.78%,respectively) were higher than those in the specimens with absence of metastasis (t=2.205, chi(2)=6.3587, chi(2)=6.2584, P<0.01, P<0.05, P<0.05, respectively). MVD and the expressions of iNOS and VEGF were not correlated to the location,size or grade of tumor,nor with the depth of invasion of tumor; MVDs in the positive iNOS and VEGF specimens(59.88+/-18.02,58.39+/-17.73, respectively) were higher than those in the negative iNOS and VEGF specimens (chi(2)=6.3587 and 6.1574, P<0.05, P<0.05,respectively);thus the expressions of iNOS and VEGF was correlated to MVD,but the expression of iNOS was not correlated to that of VEGF. In addition,of the 46 surviving patients, the 5-year survival rate of patients with positive iNOS or VEGF tumors was significantly less than that of patients with negative iNOS-or VEGF tumors(chi(2)=4.3842 and 5.4073, P<0.05, P<0.05, respectively).

Conclusion: The expressions of iNOS and VEGF are closely related to tumor angiogenesis,and are involved in the advancement and the lymph node metastasis; thus MVD and the expressions of iNOS and VEGF may serve indexes for evaluating staging of gastric carcinoma and forecasting its risk of metastasis, which will help establish a comprehensive therapeutical measure of post-operative patients and provide a new approach to tumor therapy.