Mutation and altered expression of beta-catenin during gallbladder carcinogenesis.
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.
Chang
Hee Jin
HJ
Department of Pathology, Seoul National University College of Medicine, Korea.
Jee
Chang Do
CD
Kim
Woo Ho
WH
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
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