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


CONCLUSIONS
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.
Song
Zheng-Jun
ZJ
Department of Gastroenterology,First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061, ShaanXi Province,China. gongp828@sohu.com
Gong
Ping
P
Wu
Yu-E
YE
D000328:Adult; D000368:Aged; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II