Expression and significance of hypoxia inducible factor -1 and vascular endothelial growth factor in gastrointestinal stromal tumor

Objective To investigate the expression and significance of hypoxia inducible factor 1α(HIF 1α), endothelin 1 (ET1) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST). Methods Eighty six samples of GIST specimens were collected from Xiangya Hospital (50 cases) and  Shaoyang Chinese Medicine Hospital (36 cases) from January 2003 to December 2006. The expressions of HIF 1α,  ET 1 and VEGF in the GIST were detected by immunohistochemical staininng. The relationship between HIF 1α, ET 1 and VEGF was analyzed by using the Spearman rank correlation. The survival rates were calculated by using the Kaplan－Ｍeier method, and the survival was analyzed using the Log－rank test. The count data were analyzed using the chisquare test.  Results  The expression of HIF 1α was negative in 23 cases, positive in 30 cases,  strongly positive in 33 cases, and the overall positive rate was 73.3%(63/86); the expression of ET1 was negative in 29 cases, positive in 28 cases and strongly positive in 29 cases, and the overall positive rate was  66.3%(57/86).the expression of VEGF was negative in 24 cases, positive in 26 cases, strongly positive in 36 cases, and the overall positive rate was 72.1%(62/86). There was a positive corelation between the expressions of HIF 1α, ET1 and VEGF (r=0.594, 0.655, 0.347, P<0.05). The positive expressions of HIF 1α, ET1 and VEGF were correlated with National Institute of Health (NIH) risk stratification, infiltration and metastasis, tumor diameter and number of nuclear division of GIST ( χ² =15.565, 10.841, 12.574, 21.125; 8.171, 10.002, 10.354, 17.317; 14.710, 16.230, 11.116, 18.886, P<0.05), but not with the gender, age and the initial occurring position of the tumor (χ²=0.059, 0.071, 5.070; 0.468, 0.074, 1.665; 0.231, 0.370, 3.712, P>0.05). The positive expression rates of HIF1α, ET1 and VEGF increased as the increase of the malignant level of GIST, tumor infiltration and metastasis and the tumor diameter. The follow up rate was 91.9%(79/86), and the 3 and 5　year survival rates were 82% and 69%, respectively. The median survival rate was 40.2 months (range, 2~66 months). The 5year survival rates of patients with positive expressions of HIF1α, ET1 and VEGF were 42%, 45% and 42%, respectively, and the 5　year survival rates of patients with negative expressions of HIF1α, ET1 and VEGF were 64%, 65% and 63%, respectively. The 5year survival rates of patients with positive expressions of HIF1α, ET1 and VEGF were significantly lower than those with negative expressions of HIF 1α, ET1 and VEGF（χ² =6.325, 6.124, 6.287, P<0.05). Conclusion　 There is a positive correlation between the expressions of HIF 1α, ET1 and VEGF. HIF 1α, ET1 and VEGF could be served as important predictors for the prognosis of patients with GIST.