title: Mutation and altered expression of beta-catenin during gallbladder carcinogenesis.
abstract: Gallbladder carcinoma has two main morphologic developmental pathways: a dysplasia-carcinoma sequence and an adenoma-carcinoma sequence. beta-Catenin is a key regulator of the cadherin-mediated cell adhesion system, and altered expression and mutation of beta-catenin have been identified in many human malignancies. To clarify its role in gallbladder carcinogenesis, we investigated mutation and immunohistochemical expression of beta-catenin in adenomas, dysplasias, and carcinomas. We classified adenomas according to the expression of apomucins and cytokeratin and compared the mutational and expression pattern among each type. beta-Catenin mutations were identified in 58% (14 of 24) of the adenomas, and they were absent from all carcinomas (37 cases) and dysplasias (13 cases). Altered expression of beta-catenin, such as nuclear or cytoplasmic expression and loss of membranous expression, was also significantly higher in adenomas than in dysplasias or carcinomas (p <0.001). Of the adenomas, papillary adenomas and tubular adenomas of intestinal type showed infrequent beta-catenin abnormality, which was similar to the carcinomas. The cytoplasmic and nuclear expression of beta-catenin in carcinomas was correlated with less aggressive tumor behavior; in particular, cytoplasmic expression was associated with improved patient outcome (p = 0.028). Gallbladder adenoma may be a heterogeneous entity, and the majority of adenomas are not responsible for carcinoma progression.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Chang Do
authors.initials: CD
authors.lastname: Jee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053554:Keratin-20; D008969:Molecular Sequence Data; D055272:Mucin-6; D009077:Mucins / Q000378:metabolism; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D015996:Survival Rate; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; C524734:MUC6 protein, human; D055272:Mucin-6; D009077:Mucins; D015534:Trans-Activators; D051176:beta Catenin