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Nuclear Translocation of ß-Catenin Protein but Absence of ß-Catenin and APC Mutation in Gastrointestinal Carcinoid Tumor

¹ Department of Pathology, Min-Sheng General Hospital, 168 Ching-Kuo Road, Taoyuan City, Taiwan, ROC
² Department of Gastroenterology, Buddhist Tzu Chi General Hospital Taipei Branch, 289 Jianguo Road, Xindian city, Taipei, Taiwan, ROC
³ Departments of Gastroenterology, Min-Sheng General Hospital, 168 Ching-Kuo Road, Taoyuan City, Taiwan, ROC
⁴ Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, 7, Chung-Shan South Road, Taipei, Taiwan, ROC
⁵ Department of Pathology, National Taiwan University Hospital and College of Medicine, National Taiwan University, 7, Chung-Shan South Road, Taipei, Taiwan, ROC

Correspondence: Address correspondence and reprint requests to: Ray-Hwang Yuan, MD, PhD; E-mail: yuan{at}ha.mc.ntu.edu.tw

Background: 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 ß-catenin with frequent mutations of exon 3 of ß-catenin gene in gastrointestinal carcinoid tumor has been previously described, but the role of Wnt/ß-catenin/APC pathway in the genesis of carcinoid tumor remains largely unknown.

Methods: To further characterize the role of Wnt/ß-catenin/APC pathway, we investigated 91 gastrointestinal carcinoid tumors and, for comparison, 26 extragastrointestinal carcinoid tumors by immunohistochemical detection of ß-catenin protein and direct sequencing of exon 3 of the ß-catenin gene and exon 15 of the APC gene.

Results: Cytoplasmic accumulation and/or nuclear translocation of ß-catenin were found in 27 gastrointestinal carcinoid tumors (29.7%) but not in any extragastrointestinal carcinoid tumors. Interestingly, neither ß-catenin nor APC gene mutation was detected in all of the cases with nuclear expression of ß-catenin.

Conclusions: Our results indicate that the role ß-catenin plays in the genesis of gastrointestinal and extragastrointestinal carcinoid tumors is different. Nuclear expression of ß-catenin does not occur in extragastrointestinal carcinoid tumors, and mutation of exon 3 of ß-catenin gene and exon 15 of APC gene does not contribute to the activation of Wnt/ß-catenin/APC pathway in gastrointestinal carcinoid tumors.

Key Words: Carcinoid tumors • ß-catenin mutation • APC mutation

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