组织芯片技术研究食管胃黏膜病变中Ki-67的表达及其与细胞增殖和凋亡的关系

背景：近20年来食管和食管胃连接处（EGJ）腺癌发生率呈上升趋势,Barrett食管（BE）被认为是其发生的重要危险因素。目的：应用组织芯片技术研究Ki-67在各类食管胃黏膜病变中的表达及其与细胞增殖和凋亡的关系。方法：制作140例各类食管胃黏膜组织的组织芯片,结合免疫组化方法检测Ki-67和增殖细胞核抗原（PCNA）表达。以原位末端标记技术（TUNEL法）检测BE、食管腺癌和贲门癌的细胞凋亡情况。结果：BE、食管腺癌和贲门癌组Ki-67阳性率分别为40.9%、69.6%和61.9%,均显著高于正常贲门组织（0.0%,P〈0.01）和贲门肠化生（IM）组（11.5%,P〈0.05）。BE、贲门IM、胃窦IM、食管腺癌和贲门癌组PCNA阳性率均显著高于正常贲门组织（45.5%、42.3%、39.3%、52.2%和42.9%对10.0%,P〈0.05）。BE、食管腺癌和贲门癌中Ki-67表达弱阳性和阳性者细胞凋亡指数均较表达阴性者显著降低（P〈0.05）,而PCNA仅表达阳性者凋亡指数较表达阴性者显著降低（P〈0.05）。结论：BE和EGJ处肿瘤的发生与Ki-67表达异常有关,Ki-67较PCNA更能反映EGJ处细胞凋亡状态。

Investigation of Ki-67 Expression in Esophagogastric Mucosal Lesions and its Relationship with Cell Proliferation and Apoptosis by Tissue Microarray

Background： The incidence of esophageal and esophagogastric junction （EGJ） adenocarcinomas is increasing over the last two decades. Barrett＇s esophagus （BE） is thought to be a premalignant condition of esophageal adenocarcinoma and most of adenocarcinomas at EGJ. Aims： To investigate the expression of Ki-67 in esophagogastric mucosal lesions and its relationship with cell proliferation and apoptosis by tissue microarray. Methods： Using tissue microarray technique, specimens of 140 various esophagogastric mucosal tissues were examined for Ki-67 and proliferating cell nuclear antigen （PCNA） expressions by immunohistochemical method. Cell apoptosis in BE as well as in esophageal and cardiac adenocarcinoma was determined by in situ end-labeling technique （TUNEL method）. Results： The positivity rate of Ki-67 in BE, esophageal adenocarcinoma and cardiac adenocarcinoma was 40.9%, 69.6% and 61.9%, respectively, which was significantly higher than that in normal cardiac tissue （0.0%, P〈0.01） and cardiac intestinal metaplasia （IM） tissue （11.5%, P〈0.05）. The positivity rate of PCNA in BE, cardiac IM, antral IM, esophageal adenocarcinoma and cardiac adenocarcinoma was 45.5%, 42.3%, 39.3%, 52.2% and 42.9%, respectively, which was significantly higher than that in normal cardiac tissue （10.0%, P〈0.05）. In BE, esophageal adenocarcinoma and cardiac adenocarcinoma, the cell apoptotic index in Ki-67 weakly positive and positive tissues was significantly lower than that in Ki-67 negative tissue （P〈0.05）; while the apoptotic index only in PCNA positive tissue was significantly lower than that in PCNA negative tissue （P〈0.05）. Conclusions： Abberant Ki-67 expression is involved in the development of BE and adenocarcinoma in EGJ. As compared with PCNA, Ki-67 is a more preferable marker reflecting apoptotic status in EGJ.