HIF-1α、VEGF在食管鳞癌组织中的表达及与放疗疗效的关系

The Expression of HIF-1α and VEGF in Esophageal Squamous Cancer and the Relationship with the Curative Effect of Radiotherapy

目的:探讨食管鳞状细胞癌患者缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)表达相关性及与放疗疗效的关系。方法:采用免疫组织化学SP法检测50例食管鳞状细胞癌组织标本中HIF-1α、VEGF蛋白的表达,结合临床病理特征和随访资料进行分析。结果:HIF-1α主要表达于细胞核;VEGF主要表达于细胞质,阳性表达率分别为68.0%和74.0%,两者存在显著正相关性。HIF-1α表达与临床分期、放疗近期疗效和预后有关,与病理类型、病变长度无明显关系。HIF-1α阳性组,VEGF表达强度及放疗后局部未控率均高于HIF-1α阴性组;HIF-1α阳性和阴性表达组1、2、3年生存率分别为38.2%、6.0%、0.0%和81.3%、54.2%、7.9%;HIF-1α表达阳性和阴性组食管癌患者放疗后近期完全缓解率、中位生存时间及95%的可信区间分别为18.8%、10个月(7.9,12.1)和81.3%、25个月(15.6,34.4)。结论:食管鳞状细胞癌组织中存在HIF-1α蛋白表达,HIF-1α蛋白阳性表达是食管鳞癌患者预后不良的标志,其高表达与食管鳞癌放射抗拒性有密切关系。

Objective： To analyze the expression of hypoxia inducible factor 1α （HIF-1α） and vascular endothelial growth factor （VEGF） in esophageal squamous cell cancer （ESCC） and to examine the relationship between this expression and the curative effect of radiotherapy. Methods： The expression of HIF-1α and VEGF in 50 samples of ESCC was examined using SP immunohistochemical staining and was analyzed according to the clinicopathologic features and follow-up data. Results： The positive expression rate of HIF-1α and VEGF in ESCC was 68.0% and 74.0%, respectively. The positive rate of HIF-1α was positively correlated with the presence of VEGF protein （r=0.391, P=0.005）. The positive expression of HIF-1α was closely related to clinical stage, prognosis and short-term effects of radiotherapy （P〈0.05）, but was not correlated with the pathologic type of the tumor or the size of the primary tumor （P〉0.05）. The 1-, 2- and 3-year survival rate of the patients with positive expression of HIF-1α was 38.2%, 6.0%, 0.0%, respectively, while the 1-, 2- and 3-year survival rate of the patients with no detectable expression of HIF-1α was 81.3%, 54.2%, 7.9%, respectively. The survival rate of the patients with positive expression was obviously lower compared to that of the patients with negative expression, and the difference was statistically significant （P〈0.05）. In patients with tumors positive for HIF-1α, the rate of favorable response to radiotherapy was 18.8%, and these patients had a median survival time of 10 months; in patients with tumors negative for HIF-1α, the rate of favorable response to radiotherapy was 81.3%, and these patients had a median survival time of 25 months. Conclusions： Overexpression of HIF-1α is found in ESCC. The expression of HIF-1α may serve as an important parameter for evaluating the response to radiotherapy and establishing a prognosis for patients with ESCC. It may play an important role by upregulating transcription of the VEGF gene.