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. In the current study, the authors observed expression of the CTNNB1 protein in primary pituitary adenomas to investigate the role of CTNNB1 in the development of pituitary adenomas.


METHODS
A total of 37 pituitary adenomas were analyzed. Expression of CTNNB1 and the cell proliferation marker Ki-67 were observed immunohistochemically. In addition, the authors performed direct sequencing to detect somatic mutations of exon 3 of the CTNNB1 gene.


RESULTS
Twenty-one of 37 pituitary adenomas (57%) demonstrated abnormal nuclear accumulation of CTNNB1. It is interesting to note that tumors with an accumulation of CTNNB1 in the nucleus showed a statistical tendency toward an association with increased immunoreactivity of Ki-67 (P < 0.05) whereas no significant correlation was detected between the status of CTNNB1 and other clinicopathologic features. Missense mutations in exon 3 of the CTNNB1 gene also were detected in the cases 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 adenoma in the pituitary gland.
Semba
S
S
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Han
S Y
SY
Ikeda
H
H
Horii
A
A
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis; D002467:Cell Nucleus / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010911:Pituitary Neoplasms / Q000235:genetics / Q000473:pathology*; D015534:Trans-Activators; D051176:beta Catenin
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051176:beta Catenin