Nuclear accumulation of beta-catenin in human endocrine tumors: Association with Ki-67 (MIB-1) proliferative activity

beta -Catenin is closely associated with carcinoma invasion/metastasis and poor survival. Recent studies have demonstrated that abnormal expression of beta -catenin, especially its nuclear accumulation, also plays an importan t role in wingless/Wnt signaling pathway In this study, we evaluated immuno histochemically the nuclear localization of beta -catenin in a total of 93 human-endocrine-related tumors including 1 medullary carcinoma (thyroid gla nd), 12 parathyroid tumors, 22 carcinoid tumors (digestive tract and liver) , 7 islet cell tumors, 26 adrenocortical tumors, 13 neuroblastoma (adrenal gland), and 12 pheochromocytoma (adrenal gland), and also studied genetic a lterations of the beta -catenin gene. Nuclear accumulation of beta -catenin was frequently detected in 8 of 22 (36%) carcinoid tumors and 2 of 7 (29%) islet cell tumors. No genetic alteration in exon 3 of the beta -catenin ge ne encoding serine/threonine rich domain, which was phosphorylated by GSK-3 beta, was detected in any groups of the endocrine tumors. However, nuclear accumulation of beta -catenin in carcinoid tumors was significantly correl ated with the proliferative marker Ki-67 (MIB-1) labeling index (p < 0.001) . Our findings suggest that nuclear transfer and accumulation of the <beta> -catenin may contribute in the tumorigenesis of carcinoid tumor as an oncop rotein.