Mutation and altered expression of beta-catenin during gallbladder carcinogenesis.

Department of Pathology, Seoul National University College of Medicine, Korea.
American Journal of Surgical Pathology (Impact Factor: 4.59). 06/2002; 26(6):758-66. DOI: 10.1097/00000478-200206000-00009
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the differences between images of large adenoma of the gallbladder and the protruding type carcinoma of the gallbladder. A retrospective study was performed on 130 patients who underwent cholecystectomy or biopsy for gallbladder polypoid lesions larger than 10 mm; among them, 20 patients were malignant and 110 patients were benign. Patients' details including ultrasonography (US), computed tomography (CT) and magnetic resonance (MR) findings were analyzed. All patients whose lesions were >15 mm by US, had CT or MR scans to further determine the nature of the lesion; two patients who were suspected to have a malignant lesion due to their large tumor size were benign by histological examination. Distinct differences were found between large adenoma and protruding type of gallbladder carcinoma. There were distinct differences between adenomas and the protruding type gallbladder cancers, and there was a pathological basis for the differences. Benign tumors had a more homogeneous texture, had spaces between the tumor and the gallbladder wall and a relatively normal configuration of the gallbladder wall. Based on these findings, certain lesions could be definitively diagnosed as benign adenomas and could help in treatment strategy.
    Oncology letters 05/2013; 5(5):1629-1632. DOI:10.3892/ol.2013.1248 · 0.99 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic neoplasms, including ductal adenocarcinoma, intraductal papillary mucinous neoplasm, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and ampullary carcinoma, are associated with different genetic abnormalities. Liver neoplasms, including hepatic adenomas, hepatocellular carcinomas, and cholangiocarcinomas, are associated with identifiable risk factors and genetic changes. Gall bladder adenomas and adenocarcinomas arise from distinct molecular pathways. The molecular abnormalities seen in these tumors are not used routinely in the molecular diagnostic laboratory.
    Clinics in laboratory medicine 12/2013; 33(4):875-880. DOI:10.1016/j.cll.2013.08.002 · 1.17 Impact Factor
  • Source
    Revista medica de Chile 01/2004; 132(8). DOI:10.4067/S0034-98872004000800007 · 0.37 Impact Factor