Su Min-Cheng, Wang Chia-Chi, Chen Chun-Chin, Hu Rey-Heng, Wang Ting-Huang, Kao Hsin-Lien, Jeng Yung-Ming, Yuan Ray-Hwang
Department of Pathology, Min-Sheng General Hospital, 168 Ching-Kuo Road, Taoyuan City, Taiwan, ROC.
Ann Surg Oncol. 2006 Dec;13(12):1604-9. doi: 10.1245/s10434-006-9072-2. Epub 2006 Sep 29.
Carcinoid tumors are a group of heterogeneous tumors with neuroendocrine differentiation and are mainly located in the gastrointestinal tract. A high frequency of cytoplasmic accumulation and/or nuclear translocation of beta-catenin with frequent mutations of exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor has been previously described, but the role of Wnt/beta-catenin/APC pathway in the genesis of carcinoid tumor remains largely unknown.
To further characterize the role of Wnt/beta-catenin/APC pathway, we investigated 91 gastrointestinal carcinoid tumors and, for comparison, 26 extragastrointestinal carcinoid tumors by immunohistochemical detection of beta-catenin protein and direct sequencing of exon 3 of the beta-catenin gene and exon 15 of the APC gene.
Cytoplasmic accumulation and/or nuclear translocation of beta-catenin were found in 27 gastrointestinal carcinoid tumors (29.7%) but not in any extragastrointestinal carcinoid tumors. Interestingly, neither beta-catenin nor APC gene mutation was detected in all of the cases with nuclear expression of beta-catenin.
Our results indicate that the role beta-catenin plays in the genesis of gastrointestinal and extragastrointestinal carcinoid tumors is different. Nuclear expression of beta-catenin does not occur in extragastrointestinal carcinoid tumors, and mutation of exon 3 of beta-catenin gene and exon 15 of APC gene does not contribute to the activation of Wnt/beta-catenin/APC pathway in gastrointestinal carcinoid tumors.
类癌是一组具有神经内分泌分化的异质性肿瘤，主要位于胃肠道。先前已有报道，胃肠道类癌中β-连环蛋白存在高频的细胞质积聚和/或核易位，且β-连环蛋白基因第3外显子频繁发生突变，但Wnt/β-连环蛋白/APC通路在类癌发生中的作用仍 largely 未知。
为进一步明确Wnt/β-连环蛋白/APC通路的作用，我们通过免疫组化检测β-连环蛋白蛋白，并对β-连环蛋白基因第3外显子和APC基因第15外显子进行直接测序，研究了91例胃肠道类癌肿瘤，作为对照，还研究了26例胃肠道外类癌肿瘤。
在27例胃肠道类癌肿瘤（29.7%）中发现β-连环蛋白的细胞质积聚和/或核易位，而在任何胃肠道外类癌肿瘤中均未发现。有趣的是，在所有β-连环蛋白核表达的病例中均未检测到β-连环蛋白和APC基因突变。
我们的结果表明，β-连环蛋白在胃肠道和胃肠道外类癌肿瘤发生中的作用不同。胃肠道外类癌肿瘤中未出现β-连环蛋白的核表达，且β-连环蛋白基因第3外显子和APC基因第15外显子的突变对胃肠道类癌肿瘤中Wnt/β-连环蛋白/APC通路的激活无作用。
