Molecular genetic characteristics of epithelial neoplasia of extrahepatic bile ducts

Objective. To determine the molecular genetic characteristics of the epithelial neoplasia of extrahepatic bile ducts (EHD) depending on the degree of epithelial dysplasia in order to identify mutations that facilitate their differential diagnosis. Material and methods. The study included 44 EHD biopsies containing epithelial neoplasms and cholangiocarcinoma. All samples underwent massive parallel sequencing of DNA isolated from 10-μm-thick histological sections. Mutations of categories I-III of clinical significance were considered. Statistical analysis of the obtained data utilized a two-tailed Pearson χ2 test with Holm’s correction for multiple comparisons (p<0.045). Results. The most frequent mutations in epithelial neoplasia of the EHD were identified: MYC, KRAS, PIK3CA, CDKN2A, ERBB2, KIT 6, TP53 6, FBXW7, POLE and TERT. The highest proportion of mutations was in biliary intraepithelial neoplasia and cholangiocarcinoma. Among epithelial neoplasia and cholangiocarcinoma, mutations in KRAS, POLE and TERT differed significantly. KRAS (p<0.045) — BilIN LG and BilIN HG, IPNB HG and cholangiocarcinoma; POLE (p<0.045) — BilIN LG and cholangiocarcinoma; TERT (p<0.045) — BilIN LG and cholangiocarcinoma. Specificity and sensitivity indicators for KRAS were 28 and 50%; POLE — 35 and 100%; TERT — 100 and 100%. Conclusion. Mutations have been identified that should be considered in the differential diagnosis of the degree of epithelial dysplasia and the types of epithelial neoplasia of the extrahepatic bile ducts.