食管鳞癌组织CXCR4与EMT相关因子表达及其相关性

目的研究食管鳞癌组织中细胞趋化因子受体4（CXC chemokine receptor 4,CXCR4）与上皮间质转化（epithelial-mesenchymal transition,EMT）相关因子表达情况及相关性,探讨CXCR4介导食管鳞癌转移的相关机制。方法选取2009-01-01-2011-12-31天津医科大学肿瘤医院食管肿瘤科114例经病理确诊的食管鳞癌患者手术切除存档蜡块。应用免疫组织化学法检测含114例的原发食管鳞癌组织芯片中CXCR4及EMT相关因子的表达,分析各指标与临床病理特征的相关性及CXCR4与EMT相关因子的相关性。结果食管鳞癌中CXCR4的胞质阳性表达率为62.3%（71/114）,与淋巴结转移（P=0.009）和肿瘤浸润深度（P=0.008）有关。β-catenin细胞质异常表达率为65.8%（75/114）,与肿瘤直径（P=0.045）、淋巴结转移（P=0.001）和TNM分期（P=0.005）有关。β-catenin胞膜异常表达率为64.9%（74/114）,与肿瘤部位有关（P=0.033）。Vimentin阳性表达率为31.6%（36/114）,与肿瘤淋巴结转移（P=0.013）、淋巴结转移个数（P=0.029）和TNM分期（P=0.024）有关。Logistic回归多因素分析示,CXCR4表达与淋巴结转移（P=0.030）、肿瘤浸润深度（P=0.005）、β-catenin胞质表达（P=0.011）和Vimentin的表达（P=0.022）有关。Spearman分析显示,CXCR4与β-catenin胞质表达（r=0.278,P=0.003）和Vimentin（r=0.256,P=0.006）具有相关性。结论食管鳞癌淋巴结转移过程中存在CXCR4高表达及EMT现象,且CXCL12/CXCR4生物轴介导淋巴结转移过程可能与涉及调节EMT发生有关。

Expression and relationship of CXCR4 and EMT-related factors in esophageal squamous cell carcinoma

OBJECTIVE To study the expression and relationship of CXCR4 and EMT-related factors,and investigate the regulatory mechanism of CXCR4-mediated metastasis in esophageal squamous cell carcinoma（ESCC）. METHODS The expres- sions of CXCR4 and EMT-related factors were detected by immunohistochemical staining with tissue microarray in 114 cases of primary ESCC from Tianjin Medical University, 2009-01-01 to 2011-12-31. The relationship between the expression of CXCR4 and EMT-related factors and clinical and pathological parameters were analyzed using statistical methods. The correlation between CXCR4 and EMT-related factors was analyzed with Spearman correlation analysis. RESULTS The positive expression rate of CXCR4 in the cytoplasm was 62.30% （71/114）, and it was significantly associated with tumor depth （P=0. 008） and regional lymph node metastasis （P=0. 009）. The positive rate of β-catenin in the cytoplasm was 65.8%（75/114）, and its expression was correlated with tumor size（P=0. 045）, lymph node metastasis（P=0. 001） and TNM stage（P= 0. 005）. The aberrant membranous β-catenin expression rate was 64.9 % （74/114）, and it was correlated with primary location only （P=0. 033）. The positive rate of Vimentin was 31.60% （36/114）. A correlation was also found among Vimentin,number of positive lymph nodes（P=0. 029）, lymph node metastasis（P=0. 013） and TNM stage （P=0. 024）. The Logistic regression analysis showed that expression of CXCR4 was positively correlated with lymph node metastasis （P = 0. 030）, tumor depth （P = 0. 005）, β-catenin （P = 0, 011） in the cytoplasm and Vimentin. The Spearman analysis showed that expression of CXCR4 was positively correlated with β-catenin（r= 0. 278, P=0. 003） in the cytoplasm and Vimentin（r=0. 256,P=0. 006）. CONCLUSIONS The phenomenon of EMT and high expression of CXCR4 exist in the lymph node metastasis of ESCC. This process, which was regulated by CXCL12/CXCR4 biological axis, may relate to the occurrence of EMT