Semba S, Han S Y, Ikeda H, Horii A
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Cancer. 2001 Jan 1;91(1):42-8. doi: 10.1002/1097-0142(20010101)91:1<42::aid-cncr6>3.0.co;2-7.
Beta-catenin (CTNNB1) is known to be a member of the cadherin-catenin superfamily and to function in cell-cell adhesion. However, it also has been reported that CTNNB1 plays an important role in carcinogenesis. In the current study, the authors observed expression of the CTNNB1 protein in primary pituitary adenomas to investigate the role of CTNNB1 in the development of pituitary adenomas.
A total of 37 pituitary adenomas were analyzed. Expression of CTNNB1 and the cell proliferation marker Ki-67 were observed immunohistochemically. In addition, the authors performed direct sequencing to detect somatic mutations of exon 3 of the CTNNB1 gene.
Twenty-one of 37 pituitary adenomas (57%) demonstrated abnormal nuclear accumulation of CTNNB1. It is interesting to note that tumors with an accumulation of CTNNB1 in the nucleus showed a statistical tendency toward an association with increased immunoreactivity of Ki-67 (P < 0.05) whereas no significant correlation was detected between the status of CTNNB1 and other clinicopathologic features. Missense mutations in exon 3 of the CTNNB1 gene also were detected in the cases with abnormal nuclear accumulation of the CTNNB1 protein.
The results of the current study suggest that up-regulation of the Wnt signaling pathway, including accumulation of mutant CTNNB1 in the nuclei, plays an important role in the tumorigenesis and development of adenoma in the pituitary gland.
β-连环蛋白（CTNNB1）是钙黏蛋白-连环蛋白超家族的成员，在细胞间黏附中发挥作用。然而，也有报道称CTNNB1在肿瘤发生中起重要作用。在本研究中，作者观察了CTNNB1蛋白在原发性垂体腺瘤中的表达，以探讨CTNNB1在垂体腺瘤发生发展中的作用。
共分析了37例垂体腺瘤。采用免疫组织化学方法观察CTNNB1和细胞增殖标志物Ki-67的表达。此外，作者进行直接测序以检测CTNNB1基因外显子3的体细胞突变。
37例垂体腺瘤中有21例（57%）显示CTNNB1异常核积聚。有趣的是，细胞核中CTNNB1积聚的肿瘤显示出与Ki-67免疫反应性增加相关的统计学趋势（P < 0.05），而CTNNB1状态与其他临床病理特征之间未检测到显著相关性。在CTNNB1蛋白异常核积聚的病例中也检测到CTNNB1基因外显子3的错义突变。
本研究结果表明，Wnt信号通路的上调，包括突变型CTNNB1在细胞核中的积聚，在垂体腺瘤的肿瘤发生和发展中起重要作用。
