趋化因子受体4在Barrett食管、食管腺癌和食管鳞状细胞癌中的表达及其意义

Expression of CXC chemokine receptor 4 in Barrett esophagus, esophageal adenocarcinoma and esophageal squamous cell carcinoma and its clinical significance

目的 了解趋化因子受体（CXCR4）在Barrett食管（BE）、食管腺癌和食管鳞状细胞癌中的表达,及其与病理分化程度、临床分期及淋巴结转移之间的关系.方法 应用免疫组织化学SP法对正常食管黏膜56例、BE 80例（其中伴多灶性异型增生22例）、食管腺癌25例和食管鳞状细胞癌组织48例标本中CXCR4的表达进行检测,并用仪器对表达结果进行图像分析,然后进行统计学分析.结果 （1）CXCR4在大部分BE、食管腺癌和食管鳞状细胞癌中呈阳性表达（其阳性率分别为78.8%、68.0%、83.3%）,3组间差异无统计学意义（P＞0.05）,而在正常食管黏膜组中呈阴性或弱阳性表达（阳性率为39.3%）,差异有统计学意义（P＜0.01）;（2）CXCR4在BE、食管腺癌和食管鳞状细胞癌的表达与性别、年龄、病变发生位置均无关（P＞0.05）;（3）CXCR4在BE无异型增生和BE伴多灶性异型增生组织标本中的表达差异无统计学意义（P＞0.05）;（4）CXCR4在食管腺癌高分化较中-低分化者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）;（5）CXCR4在食管鳞状细胞癌表达水平在肿瘤TNM分期的Ⅲ-Ⅳ级较Ⅰ-Ⅱ级者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）,高分化较中-低分化则明显更高（P＜0.01）.结论 CXCR4的表达上调可能是食管腺癌和鳞癌的一个普遍特征,与食管病理组织学类型无关,其表达在BE阶段就已上调,并与食管腺癌和鳞癌的分化程度,有无淋巴结转移和TNM分期有一定相关性.CXCR4的表达对BE、食管腺癌和鳞癌的诊断具有指导价值,有可能成为肿瘤治疗的一个新靶点.

Objective To investigate the expressions of CXCR4 in Barrett esophagus （BE）, esophageal adenocarcinoma （EADC） and esophageal squamous cell carcinoma （ESCC）, and its relationship with pathology, clinical staging and lymph node metastasis. Methods The expressions of CXCR4 in 56 cases of normal esophageal mucosa, 80 BE （including 22 BE with multifocal dysplasia）, 25 EADC and 48 ESCC were examined with immunohistochemical method. Results CXCR4 was expressed in most samples of BE （80. 8% ）, EADC （68. 0% ） and ESCC （78.4%） without significant difference （ P ＞ 0. 05 ）, which was significantly higher than that in normal esophageal mucosa （39. 3%, P ＜0. 01 ）. The level of CXCR4 expression in BE, EADC or ESCC were not related with gender, age, or location of the foci （ P ＞ 0. 05）. There was no significant difference in CXCR4 expression between BE without dysplasia or BE with multifocal dysplasia （ P ＞ 0. 05 ）. CXCR4 expression level in well-differentiated EADC was significantly higher than that of mild or poorly differentiated （P ＜ 0. 05 ）. CXCR4 expression level was higher in EADC with lymph node metastasis than those without （ P ＜ 0. 05 ）. CXCR4 level in ESCC with TNM staging grades Ⅲ -Ⅳ was higher than that of grades Ⅰ - Ⅱ, and this variable was also higher in cases with lymph node metastasis than those without （P ＜ 0. 05）, so was the case of well and poorly differentiated ESCC （P ＜ 0. 01 ）. Conclusion Increased expression level of CXCR4 may be a common feature of EADC and ESCC, which is irrelevant to pathological types. CXCR4 level rises at the stage of BE, which is associated with the degree of tumor differentiation, lymph node metastasis and TNM staging. CXCR4 expression is of guiding significance in the diagnosis of BE, EADC and ESCC, and is the potential drug target.