紧密连接蛋白claudin-1及Z0-1在胰腺癌中的表达

Expression of Tight Junction Associated Protein claudin-1 and ZO-1 in Pancreatic Carcinoma

目的:探讨紧密连接蛋白claudin-1及ZO-1在胰腺癌中的表达及在胰腺癌侵袭转移中的意义。方法:应用免疫组织化学方法检测claudin-1和ZO-1在胰腺癌不同侵袭位点(与非肿瘤胰腺组织相交界的胰腺癌侵袭前沿区、肿瘤中央区、与周围间质相交界的胰腺癌侵袭前沿区)及淋巴结转移灶和正常胰腺组织中的表达、结果:claudin-1与ZO-1蛋白正常定位于胰腺腺泡细胞和导管上皮细胞胞膜上,而在胰腺癌组织中,claudin-1与ZO-1蛋白定位从细胞膜异位至细胞浆或表达缺失,重度异位表达率分别为66.7%和69.2%。在与非肿瘤胰腺组织相交界处的胰腺癌组织中,低-未分化胰腺癌的claudin-1重度异位表达率(91.7%)明显高于高-中分化胰腺癌(55.6%,P<0.05);与周围间质相交界处的胰腺癌侵袭前沿区claudin-1重度异位表达率(89.7%)高于与非肿瘤胰腺组织相交界处的胰腺癌侵袭前沿区(66.7%,P<0.05);淋巴结转移灶重度异位表达率最高(92.3%,P<0.05)。同样与周围间质相交界处的胰腺癌侵袭前沿区ZO-1重度异位表达率(94.9%)也高于与非肿瘤胰腺组织相交界处的胰腺癌侵袭前沿区(64.2%,P<0.05),淋巴结转移灶最高(100%,P<0.05);原发胰腺癌组织各个位点中claudin-1与ZO-1表达呈正相关关系。结论:claudin-1和ZO-1异位表达对胰腺癌的发生起促进作用;clauclin-1异位表达与胰腺癌的分化有关;claudin-1和ZO-1异位表达率增加促进胰腺癌的侵袭与转移。

Objective： To investigate the expression of tight junction associated protein claudin-1 and ZO-1 in pancreatic carcinoma and its significance in the invasion and metastasis of pancreatic carcinoma. Methods： Immunohistochemistry was used to detect the expression of claudin-1 and ZO-1 in different sites of pancreatic carcinoma, including the front-edge area of the pancreatic carcinoma on the borderline to the normal pancreatic tissue, the central area of the carcinoma, the front edge of the tumor adjacent to the peripheral mesenchymal tissue and the normal pancreatic tissue. Results： In the normal pancreatic tissue, claudin-1 and ZO-1 were located in the membrane of pancreatic gland alveolus and ductal epithelial cells, but in the pancreatic carcinoma tissue, expression of severe aberrant immunostaining was seen in 66.7% of claudin-1 and 69.2% of ZO-I. The severe ectopic expression rate of claudin-1 of the poorly and undifferentiated pancreatic carcinomas was obviously higher in the tissue of the pancreatic carcinoma adjacent to the normal pancreatic tissue （91.7%） than in the well-differentiated pancreatic carcinoma （55.6%, P〈0.05）. The severe ectopic expression rate of claudin-1 was higher in the front edge area of pancreatic carcinoma adjacent to the peripheral mesenchymal tissue （89.7%） than in the pancreatic carcinoma next to the normal pancreatic tissue （66.7%, P〈0.05）. The severe ectopic expression ranked the highest in the lymph node metastases （92.3%, P〈0.05）. Also, the severe ectopic expression rate of ZO-1 was higher in the invasive front edge of pancreatic carcinoma adjacent to the peripheral mesenchymal tissue （94.9%） than in the pancreatic carcinoma next to the normal pancreatic tissue （64.2%, P〈0.05）. The severe ectopic expression ranked the highest in the lymph node metastases （100%, P〈0.05）. There was a positive correlation between the claudin-1 and ZO-1 expressions in various sites of the pancreatic carcinomas. Conclusion： The aberrant expression of claudin-1 and ZO-1 may promote the tumorigenesis and development of pancreatic carcinoma. The aberrant claudin-1 expression is in relation to the differentiation of pancreatic carcinoma. The ectopic expressions of claudin-1 and ZO-1 may facilitate the invasion and metastasis of pancreatic carcinoma.