缺氧诱导因子1α和血管内皮素1及血管内皮生长因子在胃肠道间质瘤中的表达及意义

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

    摘要
  • 摘要:

     目的　探讨缺氧诱导因子 1α(HIF 1α)、血管内皮素 1(ET 1)和血管内皮生长因子(VEGF) 在胃肠道间质瘤(GIST)中的表达关系及其对患者预后判断的价值。方法　收集2003年1月至2006年12月中南大学湘雅医院(50例)、湖南省邵阳市中医院(36例)行手术治疗的86例GIST患者肿瘤标本，采用免疫组织化学染色方法检测标本中HIF 1α、ET1和VEGF的表达。计数资料采用χ2 检验，应用Spearman等级相关分析处理HIF 1α、ET1和VEGF之间的相关性。Kaplan－Meier法计算患者生存率，生存分析比较采用Log－rank检验。结果 86例患者中，HIF 1α阴性23例、阳性30例、强阳性33例，阳性表达率为73.3%(63/86)；ET1阴性29例、阳性28例、强阳性29例，阳性表达率为66.3%(57/86)；VEGF阴性24例、阳性26例、强阳性36例，阳性表达率为72.1%(62/86)。HIF 1α、ET 1和VEGF的表达两两均呈正相关( r=0.594，0.655，0.347，P<0.05)；上述3种检测指标与GIST的美国国立卫生研究院(NIH)危险度分级、浸润转移、肿瘤直径和核分裂象有关(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)；而与患者的性别、年龄、肿瘤原发部位无关(χ2=0.059、0.071、5.070，0.468、0.074、1.665，0.231、0.370、3.712， P>0.05)；进一步分析发现：上述3种检测指标阳性表达率随GIST NIH危险度分级的升高、出现浸润转移和肿瘤直径的增大而增加。86例患者随访率为91.9%(79/86)，3、5 年生存率分别为82%和69%。中位随访时间为40.2个月(2～66个月)。HIF1α、ET1和VEGF阳性患者的5年生存率分别为42%、45%和42%，显著低于阴性患者的64%、65%和63%(χ2=6.325，6.124，6.287， P<0.05)。结论　HIF1α、ET1和VEGF在GIST中的表达两两呈正相关，这3种检测指标提示肿瘤的恶性程度及患者预后。

     

    Abstract:

    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.

     

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