鳞癌中缺氧诱导因子-1α、血管生成因子在食管鳞癌中的表达及临床病理意义  

Expression of hypoxia-inducible factor-1α and vessel endothelial growth factor in esophageal squamous cell carcinoma and clinico-pathological significance thereof

作　　者：于振涛[1] 赵华锋[1] 尚晓滨[1] 赵锡江[1] 

机构地区：[1]天津医科大学附属肿瘤医院食管肿瘤科,300060

出　　处：《中华医学杂志》2008年第35期2465-2469,共5页National Medical Journal of China

基　　金：天津市自然科学基金资助项目（05YFJMJC14600）

摘　　要：目的探讨食管鳞癌中缺氧诱导因子（HIF-1α）和血管生成因子（VEGF）的表达及其与临床病理之间的关系。方法采用荧光定量RT—PCR和免疫组化分别测定食管鳞癌组织和切端正常组织HIF-1α、VEGF表达水平。对比分析HIF-1α、VEGF在食管鳞癌组织和正常切端中的表达以及HIF-1α和VEGF与肿瘤侵犯深度、淋巴结转移（含淋巴侵犯）、肿瘤组织分化程度之间的关系。结果HIF-1αmRNA在食管鳞癌组织中的相对表达量为5．88±1．12，在食管切端正常组织中的相对表达量为4．76±1．26，前者明显高于后者（P=0．014）；VEGF mRNA在食管鳞癌组织中相对表达量为12．79±2．51，在食管切端切正常组织中的相对表达量为10．92±2．23，前者明显高于后者（P=0．010）；食管鳞癌组织中HIF-1α蛋白质阳性率50％（21／42），明显高于正常切端组织的14％（6／42）；VEGF蛋白质阳性率76％（32／42），明显高于正常切端组织的33％（14／42）。HI-1α mRNA、VEGF mRNA表达趋向于与淋巴结转移相关（分别P=0．073、P=0．063）。HIF-1α蛋白质表达在胞核和（或）胞质中，HIF-1α蛋白表达与淋巴结转移及淋巴侵犯、肿瘤组织分化相关（分别P=0．013、P=0．028）。但没有发现HIF-1αmRNA与VEGF蛋白之间有显著相关性。结论肿瘤组织中HIF-1α除蛋白质水平受缺氧调节外，还可能存在转录及转录后水平调节；通过对HIF-1α与临床病理关系的研究表明HIF-1α亦与淋巴结转移和肿瘤组织分化程度密切相关。因此，HIF-1α与VEGF有可能作为反映食管癌诊断及进展的生物学指标，成为抗血管生成治疗的靶点。Objective To investigate the expression of hypoxia-inducible factor （HIF）-1αtand vessel endothelial growth factor （VEGF） and their relations with the clinicopathological features of esophageal squamous cancer. Methods Esophageal squamous cancer tissues and normal end squamous epithelium tissues were collected from 42 patients during operation. Real-time quantitative PCR was used to detect the mRNA expression of HIF-1α and VEGF and immunohistochemistry was used to detect the protein expression of HIF-1α and VEGF. The relations between the expression of HIF-1α, VEGF and depth of tumor invasion, histological grade, lymphatic invasion, and lymph node metastasis were evaluated. Results The HIF-1α mRNA expression level was 5.88 ± 1.12 in the esophageal squamous cancer tissue, higher, but not significantly, than that in normal end squamous epithelium tissue 4. 76 ±1.26 （ P = 0. 014 ）. The VEGF mRNA expression level in the esophageal squamous cancer tissue was 12. 79 ±2. 51, higher, but not significantly, than that in the normal end squamous epithelium tissue （ 10. 92 ±2. 23,P = 0. 010）. The HIF-1α and VEGF protein positive rates in esophageal squamous cancer tissue were 50% （21/42）and 76% （32/ 42） respectively, significantly higher than those in the normal esophageal tissue [ 14% （6/42）and 33% （14/42） respectively,P = 0. 001, P = 0. 000 ]. The expression of HIF-1α mRNA and VEGF mRNA in the esophageal squamous cancer were correlated with lymph node metastasis （including lymphatic invasion ） （P =0. 063 and P = 0. 073 respectively）. HIF-1α immunoreactivity was localized in the nucleus and/or cytoplasm of the cancer cells. The expression of HIF-1α protein was correlated with lymph node metastasis and histological grade （P = 0. 013 and P = 0. 028 respectively）. No correlation was found between HIF-1α mRNA and VEGF protein. Conclusion HIF-1α may be regulated at transcription and post-transcription levels in addition to protein level. It also plays an important role in

关 键 词：癌 鳞状细胞 食管肿瘤 血管生成因子 缺氧诱导因子-1Α 

分 类 号：R686[医药卫生—骨科学]