Xu Bing, Sano Toshiaki, Yoshimoto Katsuhiko, Yamada Shozo
Department of Pathology, University of Tokushima School of Medicine, Tokyo, Japan.
Endocr Pathol. 2002 Winter;13(4):341-51. doi: 10.1385/ep:13:4:341.
The cadherin-catenin complex regulates cellular adhesion and motility, and genetic alterations in these molecules play a critical role in multistage tumorigenesis. In this study, the expression of three major type I classic cadherins E-, N-, and P-cadherin and their undercoat proteins alpha-, beta-, and gamma-catenin, and pp120 was investigated in 127 pituitary adenomas and 10 normal adenohypophyseal glands using an immunohistochemical technique with highly specific monoclonal antibodies. In normal pituitary glands, E-cadherin, catenins, and pp120 were strongly expressed on almost all hormone-producing cell-cell boundaries, N-cadherin was weakly immunoreactive on a few cell-cell boundaries, and P-cadherin was negative. In pituitary adenomas, a correlation was not identified among expression of E-cadherin, catenins, or pp120 with patient age, sex, hormone level, tumor size, and/or invasiveness, respectively. Expression of E-cadherin, catenins, and pp120 was significantly reduced in 24 growth hormone (GH) cell adenomas with prominent fibrous bodies compared with the other subtypes of pituitary adenomas and normal pituitary glands (p < 0.0001, respectively). Methylation-specific polymerase chain reaction analysis revealed that the E-cadherin gene promoter region was methylated in 6 of 16 (37.5%) GH cell adenomas with prominent fibrous bodies examined, 2 of which displayed total methylation, but not in 10 GH cell adenomas without fibrous bodies. No mutation of exon 3 of the beta-catenin gene was found in 16 GH cell adenomas with prominent fibrous bodies or in 10 other subtypes of pituitary adenomas that showed unremarkable intracellular presence of beta-catenin protein. In conclusion, the decreased expression of the E-cadherin catenin complex and methylation of the E-cadherin gene promoter region only in GH cell adenomas with prominent fibrous bodies may be an event associated with the formation of fibrous bodies.
钙黏蛋白 - 连环蛋白复合体调控细胞黏附和运动，这些分子的基因改变在多阶段肿瘤发生中起关键作用。在本研究中，使用具有高度特异性的单克隆抗体的免疫组织化学技术，对127例垂体腺瘤和10个正常腺垂体中三种主要的I型经典钙黏蛋白E - 钙黏蛋白、N - 钙黏蛋白和P - 钙黏蛋白及其底层蛋白α - 连环蛋白、β - 连环蛋白、γ - 连环蛋白和pp120的表达进行了研究。在正常垂体中，E - 钙黏蛋白、连环蛋白和pp120在几乎所有产生激素的细胞 - 细胞边界上强烈表达，N - 钙黏蛋白在少数细胞 - 细胞边界上弱免疫反应，而P - 钙黏蛋白为阴性。在垂体腺瘤中，E - 钙黏蛋白、连环蛋白或pp120的表达与患者年龄、性别、激素水平、肿瘤大小和/或侵袭性之间未发现相关性。与其他垂体腺瘤亚型和正常垂体相比，24例具有明显纤维小体的生长激素（GH）细胞腺瘤中E - 钙黏蛋白、连环蛋白和pp120的表达显著降低（分别为p < 0.0001）。甲基化特异性聚合酶链反应分析显示，在检测的16例具有明显纤维小体的GH细胞腺瘤中有6例（37.5%）E - 钙黏蛋白基因启动子区域发生甲基化，其中2例显示完全甲基化，但在10例无纤维小体的GH细胞腺瘤中未发现甲基化。在16例具有明显纤维小体的GH细胞腺瘤或10例其他垂体腺瘤亚型中，未发现β - 连环蛋白基因第3外显子的突变，这些垂体腺瘤亚型中β - 连环蛋白蛋白在细胞内的表达不明显。总之，仅在具有明显纤维小体的GH细胞腺瘤中E - 钙黏蛋白 - 连环蛋白复合体表达降低以及E - 钙黏蛋白基因启动子区域甲基化可能是与纤维小体形成相关的事件。
