Tobioka Hirotoshi, Isomura Hiroshi, Kokai Yasuo, Tokunaga Yuichi, Yamaguchi Jun, Sawada Norimasa
Department of Pathology, Sapporo Medical University School of Medicine, Japan.
Hum Pathol. 2004 Feb;35(2):159-64. doi: 10.1016/j.humpath.2003.09.013.
The tight junctions of the glandular epithelium are crucial for the maintenance of cell polarity, separating the plasma membrane into apical and basolateral domains. Thus abnormalities of the tight junctions may result in the structural disturbances of glandular epithelial neoplasia. In this study we introduced an anti-occludin monoclonal antibody for semiquantitative assay of the occludin expression in tissue sections of human normal and neoplastic endometrial epithelia using the Adobe Photoshop and NIH Image programs. Normal endometrial glands and samples of endometrial hyperplasia and endometrioid carcinoma grade 1 fully expressed occludin at the apical cell border. In endometrioid carcinomas grades 2 and 3, however, occludin disappeared in solid areas of the carcinomatous tissues. Occludin was also found at the apical borders of the cancer cells that formed glandular structures. Occludin expression decreased progressively in parallel with the increase in carcinoma grade, and the decreased occludin expression correlated with myometrial invasion and lymph node metastasis. These results suggest that the loss of tight junctions has a close relationship with structural atypia in the progression of human endometrial carcinomas and their malignant potential.
腺上皮的紧密连接对于维持细胞极性至关重要,它将质膜分隔为顶端和基底外侧结构域。因此,紧密连接异常可能导致腺上皮肿瘤形成结构紊乱。在本研究中,我们引入一种抗闭合蛋白单克隆抗体,使用Adobe Photoshop和NIH Image程序对人正常及肿瘤性子宫内膜上皮组织切片中的闭合蛋白表达进行半定量分析。正常子宫内膜腺体以及子宫内膜增生和1级子宫内膜样癌样本在顶端细胞边界处均充分表达闭合蛋白。然而,在2级和3级子宫内膜样癌中,癌组织实性区域的闭合蛋白消失。在形成腺结构的癌细胞顶端边界也发现了闭合蛋白。闭合蛋白表达随癌分级增加而逐渐降低,且闭合蛋白表达降低与肌层浸润和淋巴结转移相关。这些结果表明,紧密连接的丧失与人类子宫内膜癌进展中的结构异型性及其恶性潜能密切相关。