Expressions And Clinical Significance Of Hypoxia Inducible Factor-1α And Vascular Endothelial Growth Factor In Gastric Cancer

【Objective】The aim of this study was to investigate the expression of HIF-1 , VEGF and MVDin gastric carcinoma and study their correlation with clinical pathological features suchas cancer invasion and metastasis.And provide valuable markers for invasion,metatasisand prognosis of gastric cancer.【Methods】The expression of HIF-1 and VEGF was investigated by immunohistochemistry in74 specimens of gastric carcinoma. Immunohistochemical staining for the CD34endothelial antigen, which was identified by SP immunohistochemical method, wasperformed to highlight the new growth microvessels and the microvessel density oftumor was calculated.【Results】1.The expression of HIF-1 in gastric carcinomaHIF-1 protein expression was brown granular, and mainly localized in cytoplasmand minor staining was also detected in nucleus of tumor cells.The distribution ofHIF-1 positive cells was heterogeneous and strong expression was frequentlyobserved at the invading edge of tumor margins and the periphery of necrotic regions.The positive rate of HIF-1 staining was 50.95%.2. Relationship between expression of HIF-1 the clinicopathologic parameters ingastric carcinoma.The positive expression of HIF-1 was significantly related to the depth of tumorinfiltration, lymph node metastasis,TNM staging and histological differentiation(rs=0.306, 0.399, 0.315, 0.268), but no significant correlation was found between thepositive rate of HIF-1 staining and the age and gender of patients, size, tumor locationand Borrmann's classification. (P>0.05).3. Relationship between expression of HIF-1 the clinicopathologic parameters ingastric carcinoma. The 1, 3, 5-year survival rate after operation was significantly lower in patientswith HIF-1 positively staining than that of patients with HIF-1 negative (52.27%,36.36%, vs 76.6%, 60%, 46.67%, respectively ,P<0.05, log-rank test).Multivariate Coxproportional hazards model analysis identified HIF-1 expression as an independentprognostic indicator of survival(P=0.004, relative risk=0.516).4. Relationship between expression of HIF-1 and VEGF in gastric carcinoma VEGF protein expression was brown granular, and mainly localized in cytoplasmand minor staining was also detected in membrane of tumor cells .The distribution ofVEGF positive cells was also heterogeneous.The positive rate of VEGF staining was64.86%. The positive rate of VEGF staining increased significantly with thestrengthened staining of HIF-1 expression(P<0.01).Spearman rank correlation testshowed a positive correlation between HIF-1 expression and the positive rate of VEGFstaining (rs=0.591, P <0.01).4.1Relationship between expression of HIF-1 and MVD in gastric carcinoma MVD in HIF-1 positive group was 53.70±9.989, which was higher than that ofHIF-1 negative group 36.24±6.25(P<0.05).Spearman rank correlation test showed apositive correlation between HIF-1 expression and MVD( rs=0.754, P<0.01).4.2Relationship between expression of VEGF and MVD in gastric carcinoma MVD in VEGF positive group was 50.62±10.42, which was higher than that ofVEGF negative group 41.88±14.41( P<0.01).4.3 Relationship between coexpression of VEGF and HIF-1 , MVD in gastriccarcinoma MVD in group of both positive expression of HIF-1 and VEGF was 53.50±9.04,in group of single positive expression of HIF-1 or VEGF was 45.15±12.84, in groupof both negative expression of HIF-1 and VEGF was 35.93±6.98.There wassignificant difference between the three groups (P<0.01).【Conclusions】1. HIF-1 protein was overexpressed in gastric carcinoma, and its overexpression was significantly associated with depth of invasion, lymph node metastasis, TNM staging and histological differentiation and served as an independent marker for prognosis of gastric carcinoma.2. VEGF protein expression was positively associated with HIF-1 expression. Overexpression of HIF-1 and VEGF protein might play synergetic roles in the process of carcinogenesis of gastric carcinoma.3. MVD was positively associated with coexpression of HIF-1a and VEGF .HIF-1a /VEGF pathway-mediated angiogenesis may plays an important role in invasion and metastasis of gastric carcinoma.