食管鳞癌及癌前病变组织中紧密连接蛋白claudin3和4的表达及临床病理意义

Expression and clinicopathological significance of claudin 3 and 4 in esophageal squamous carcinoma and precancerous lesion

目的检测紧密连接蛋白claudin3、claudin4在食管鳞状细胞癌及癌前病变组织中的表达,探讨二者表达的临床病理学意义。方法应用组织芯片联合免疫组化EnVision法检测claudin3、claudin4在93例食管鳞癌、20例异型增生组织、20例食管炎和15例正常食管上皮组织中的表达水平。结果 claudin3在正常食管上皮、食管炎、异型增生及食管鳞癌中的表达率分别为6.7%(1/15)、20.0%(4/20)、30.0%(6/20)、43.0%(40/93),癌组织阳性率最高,正常食管上皮组织阳性率最低,差异有统计学意义(P<0.05),食管癌阳性率较正常食管上皮明显升高(P<0.05),异型增生及食管炎的表达较正常组织差异并无显著性(P>0.05)。claudin4在正常食管上皮、食管炎、异型增生及食管鳞癌中的表达率分别为33.3%(5/15)、35.0%(7/20)、40.0%(8/20)、45.2%(42/93),各组间差异无统计学意义(P>0.05)。claudin3和claudin4表达与患者的性别、年龄、肿瘤大小、病理分级及浸润深度无相关性(P>0.05),但有淋巴结转移者的阳性率较无淋巴结转移者低(P<0.05),且死亡组的阳性率较生存组低(P<0.05);claudin3和claudin4在食管鳞癌中表达存在显著相关性(χ2=8.520,K=0.302,P=0.004),但两种表达无统计学差异(P>0.05);生存分析发现claudin3和claudin4表达阳性组的术后生存率高于表达阴性组(P<0.05)。结论 claudin3可能参与了食管鳞癌的发生,有淋巴结转移时claudin3和claudin4的表达出现下调,claudin3和claudin4有可能成为判断食管鳞癌预后的分子标志物。

Objective To determine the expression of claudin 3 and claudin 4 in esophageal squamous carcinoma and its precancerous lesion, and investigate the clinicopathological significance of the expression. Methods Tissue microarray technology and immunohistochemical assay （Envision） were used to detect the expression of claudin 3 and 4 in 93 tissue samples of esophageal squamous carcinoma, 20 samples of dysplasia, 20 samples of esophagitis and 15 cases of normal esophageal mucosal tissues. Results Claudin 3 was expressed in only 1 case of normal esophageal mucosa （6.7%）, 4 cases of esophagitis （20.0%）, 6 cases of dysplasia （30.0%） and 40 cases of squamous carcinoma （43.0%）. The positive rate was the highest in cancer tissue, and the lowest in normal esophageal tissue, with significant difference between them （P〈0.05）. The rate was obviously higher in the cancer tissue than in normal tissue （P〈0.05）, but no difference was seen among the normal tissue, dysplasia and esophagitis tissue （P〉0.05）. Claudin 4 expression was found in 5 cases of normal esophageal mucosa （33.3%）, 7 cases of esophagitis （35.0%）, 8 cases of dysplasia （40.0%） and 42 cases of squamous carcinoma （45.2%）, without significant difference among these groups （P〉0.05）. The expression of claudin 3 and 4 was not associated with other clinicopathologic factors, such as sex, age, tumor size, pathological grade and infiltration （P〉0.05）, but obviously negatively associated with lymphatic metastasis and patient survival （P〈0.05）. The expression of claudin 3 and 4 was significantly correlated with each other （Chi-sqaure=8.520, K=0.302,P=0.004）, but had no significant difference in esophageal squamous carcinoma （P〉0.05）. Kaplan-Meier survival analysis showed that the survival rate in patients with claudin3 and 4 expression was significantly higher than those without （P〈0.05）. Conclusion Claudin 3 may participate in the occurrence of esophageal squamous carcinoma. Down-regulation of claudin 3 and 4 is associated with lymphatic metastasis in esophageal squamous carcinoma, and they might serve as potential markers for prognosis of esophageal squamous carcinoma.