Nuclear translocation of beta-catenin protein but absence of beta-catenin and APC mutation in gastrointestinal carcinoid tumor.

Abstract

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.