BNIP3 HIF-1α在食管鳞癌中的表达及其临床病理意义＊

Expression and clinical significance of BNIP3 and HIF-1α in esophageal squamous cell carcinoma

目的:初步探讨BCL-2/腺病毒E1B 19 kDa相关蛋白3(BCL2/adenovirus E1B19 kd-interacting protein3,BNIP3)和乏氧诱导因子-1α(HIF-1α)在食管鳞癌(ESCC)中表达及其与临床病理之间的关系和意义。方法:采用免疫组织化学S-P方法分别测定食管鳞癌组织和切端正常食管黏膜组织芯片的BNIP3、HIF-1α的表达水平。运用统计学方法对比分析BNIP3和HIF-1α在食管鳞癌组织和切端正常黏膜组织中的表达以及BNIP3和HIF-1α与肿瘤原发病灶部位、肿瘤浸润深度(T分期)、TNM分期、淋巴结转移(含淋巴侵犯)、肿瘤组织分化程度(分级)等临床病理特征之间的关系。结果:BNIP3表达在细胞质中,HIF-1α表达在细胞核和细胞质中。食管鳞癌组织中BNIP3蛋白表达阳性率37.5%(27/72),明显低于正常切端组织的60%(18/30)(P=0.037);HIF-1α蛋白表达阳性率52.7%(38/72),明显高于正常切端组织的13.3%(4/30)(P<0.001)。BNIP3蛋白表达与食管癌的肿瘤浸润深度、TNM分期、淋巴结转移相关(P=0.035、P=0.048、P=0.033)。HIF-1α蛋白表达亦与肿瘤浸润深度、TNM分期、淋巴结转移相关(P=0.023、P=0.004、P=0.002)。并且,BNIP3表达与HIF-α表达呈负相关(r=-0.274,P=0.020)。结论:在食管鳞癌中,BNIP3与HIF-1α的表达密切相关,且均与肿瘤的浸润深度、TNM分期、淋巴结转移密切相关。因此,联合检测BNIP3和HIF-1α,有助于食管鳞癌的辅助诊断、病期评价及预后判断。

Objective：This study aimed to preliminarily investigate the expression and clinical significance of BCL2/adenovirus E1B 19 kd-interacting protein 3 （BNIP3） and hypoxia inducible factor-1α（HIF-1α） in esophageal squamous cell carcinoma （ESCC）. Methods：The expressions of BNIP3 and HIF-1αwere detected by immunohistochemical staining with tissue microarray in 72 cases of ESCC and 30 cases of normal esophageal mucosa tissue. BNIP3 and HIF-1αexpressions were compared in ESCC and normal esophageal mucosa tissue using statistical methods. The relationship between BNIP3 and HIF-1α, as well as clinical pathological features including the original site of tumor, tumor infiltration depth （T stage）, TNM staging, lymph node metastasis （including lymphatic invasion） and tumor differentiation （grade）, were statistically analyzed. Results：BNIP3 protein expression was localized in the cytoplasm of cells. HIF-1αprotein expression was localized in the nucleus and cytoplasm of cells. The positive ratio of BNIP3 protein in esophageal squamous cell carcinoma tissue was 37.5%（27/72）, which was significantly lower than that in normal esophageal mucosa tissue which was 60%（18/30） （P=0.037）. The positive ratio of HIF-1αprotein in ESCC was 52.7%（38/72）, which was significantly higher than that in normal esophageal mucosa tissue at 13.3%（4/30） （P=0.000）. The expression of BNIP3 protein was correlated with the depth of tumor invasion, TNM stage, and lymph node metastasis （P=0.035, P=0.048, P=0.033）. The expression of HIF-1αprotein was also correlated with depth of tumor invasion, TNM stage, and lymph node metastasis （P=0.023, P=0.004, P=0.002）. The expression of BNIP3 protein was positively correlated with HIF-1α（r=-0.274, P=0.020）. Conclusion：The expression of BNIP3 is correlated with HIF-1αexpression, depth of tumor invasion, TNM stage, and lymph node metastasis in ESCC. Therefore, the combined detection of BNIP3 and HIF-1αmay contribute to the auxiliary diagnosis, prediction of prognosis, and monitoring of postoperative recurrence in ESCC.