Histologic and Molecular Pathogenesis of Gallbladder Cancer
10.15279/kpba.2018.23.1.1
- Author:
Kyoung Bun LEE
1
Author Information
1. Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. kblee@snuh.org
- Publication Type:Review
- Keywords:
Gallbladder neoplasms;
Adenocarcinoma;
Precancerous conditions;
Mutation;
Carcinogenesis
- MeSH:
Adenocarcinoma;
Adenoma;
Bile Pigments;
Carcinogenesis;
Carcinoma in Situ;
Cholecystitis;
Diagnosis;
DNA, Mitochondrial;
Epithelial Cells;
Epithelium;
Gallbladder Neoplasms;
Gallbladder;
Hyperplasia;
Loss of Heterozygosity;
Mucins;
Mucous Membrane;
Precancerous Conditions;
Risk Factors
- From:Korean Journal of Pancreas and Biliary Tract
2018;23(1):1-6
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Adenocarcinoma is the major histology of gallbladder cancer. There are three subtypes of adenocarcinoma of the gallbladder: biliary, intestinal, and gastric foveolar subtypes. Also, there are three premalignant lesions of gallbladder adenocarcinoma: adenoma, biliary intraepithelial neoplasia (BilIN), and intracystic papillary neoplasm (ICPN). Premalignant lesion is hyperplasia of dysplastic epithelial cells with no evidence of stromal invasion. BilIN is invisible in gross inspection but can be microscopically identified around invasive tumor or chronic cholecystitis. ICPN is grossly identified as exophytic polypoid mass or diffuse friable thickening of mucosa and composed of mucinous epithelial cells with papillary and tubular arrangement. Dysplasia of BilIN and ICPN is classified by using a three-tiered system and high grade dysplasia is the same group with carcinoma in situ. Adenoma and ICPN have some ambiguities in definition and re-establishment of diagnostic criteria is needed for reproducibility of diagnosis. KRAS, TP53, and CDKN2A are the representative altered molecules in gallbladder cancer. Molecular alteration during dysplasia-carcinoma sequence is too heterogenous depending to the risk factors and type of premalignant lesion to explain the whole process by single process. Over-expression of COX2, mutation of TP53, impairment of mitochondrial DNA were reported in early hyperplastic or metaplastic epithelium. Loss of heterozygosity (LOH) of 3p, 8p chromosomes and amplification of HER2 were reported in low grade dysplasia and LOH of 9p, 18q, 22q, 17p chromosomes and mutation of CDK2A were reported in high grade dysplasia/carcinoma in situ.
