Frequent nuclear accumulation of beta-catenin in pituitary adenoma

BACKGROUND. 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, I n the current study, the authors observed expression of the CTNNB1 protein in primary pituitary adenomas to investigate the role of CTNNB1 in the deve lopment of pituitary adenomas. METHODS. A total of 37 pituitary adenomas were analyzed. Expression of CTNN B1 and the cell proliferation marker Ki-67 were observed immunohistochemica lly. In addition, the authors performed direct sequencing to detect somatic mutations of exon 3 of the CTNNB1 gene. RESULTS. Twenty-one of 37 pituitar y adenomas (57%) demonstrated abnormal nuclear accumulation of CTNNB1. It i s interesting to note that tumors with an accumulation of CTNNB1 in the nuc leus showed a statistical tendency toward an association with increased imm unoreactivity of Ki-67 (P <; 0.05) whereas no significant correlation was d etected between the status of CTNNB1 and other clinicopathologic features. Missense mutations in exon 3 of die CTNNB1 gene also were detected in the c ases with abnormal nuclear accumulation of the CTNNB1 protein. CONCLUSIONS. 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 ade noma in the pituitary gland.