Matsubara Daisuke, Kishaba Yuka, Yoshimoto Taichiro, Sakuma Yuji, Sakatani Takashi, Tamura Tomoko, Endo Shunsuke, Sugiyama Yukihiko, Murakami Yoshinori, Niki Toshiro
Molecular Pathology Laboratory, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Integrative Pathology, Jichi Medical University, Tochigi, Japan.
Pathol Int. 2014 Nov;64(11):560-8. doi: 10.1111/pin.12214. Epub 2014 Oct 27.
We performed an immunohistochemical analysis of the expression of zinc-finger E-box binding homeobox 1 (ZEB1), a master regulator of epithelial-mesenchymal transition (EMT), and determined its relationship with E-cadherin in 157 non-small cell lung carcinomas (93 adenocarcinomas, 36 squamous cell carcinomas, 18 large cell carcinomas, and 10 pleomorphic carcinomas). Although the expression of E-cadherin was low in the subset of adenocarcinomas (10%) and squamous cell carcinomas (11%), ZEB1 expression was only observed in one case of squamous cell carcinoma and none of the adenocarcinomas. In contrast, the low expression of E-cadherin (50% and 90%, respectively) and the positive expression of ZEB1 (11% and 50%, respectively) were more frequently observed in poorly differentiated carcinomas (large cell carcinomas and pleomorphic carcinomas). Overall, the expression of ZEB1 was inversely correlated with that of E-cadherin. Furthermore, the distribution of ZEB1-positive cancer cells was more restricted than in the area in which the expression of E-cadherin was lost, and the former was detected within the latter. We concluded that the expression of ZEB1 was not necessarily associated with the low expression of E-cadherin in lung adenocarcinomas and squamous cell carcinomas. The expression of ZEB1 correlated with an undifferentiated and/or sarcomatoid morphology that may occur in the late stage of EMT.
我们对锌指E盒结合同源框1（ZEB1）的表达进行了免疫组织化学分析，ZEB1是上皮-间质转化（EMT）的主要调节因子，并确定了其与157例非小细胞肺癌（93例腺癌、36例鳞状细胞癌、18例大细胞癌和10例多形性癌）中E-钙黏蛋白的关系。尽管腺癌亚组（10%）和鳞状细胞癌亚组（11%）中E-钙黏蛋白的表达较低，但仅在1例鳞状细胞癌中观察到ZEB1表达，而腺癌中均未观察到。相反，在低分化癌（大细胞癌和多形性癌）中更频繁地观察到E-钙黏蛋白的低表达（分别为50%和90%）和ZEB1的阳性表达（分别为11%和50%）。总体而言，ZEB1的表达与E-钙黏蛋白的表达呈负相关。此外，ZEB1阳性癌细胞的分布比E-钙黏蛋白表达缺失区域更局限，且前者在后者区域内被检测到。我们得出结论，在肺腺癌和鳞状细胞癌中，ZEB1的表达不一定与E-钙黏蛋白的低表达相关。ZEB1的表达与EMT后期可能出现的未分化和/或肉瘤样形态相关。
