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Distinctive clinicopathological features and KRAS and IDH 1/2 mutation status of cholangiolocellular carcinoma
Author(s) -
Kusano Hironori,
Naito Yoshiki,
Mihara Yutaro,
Kondo Reiichiro,
Ogasawara Sachiko,
Akiba Jun,
Nakashima Osamu,
Yano Hirohisa
Publication year - 2020
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13428
Subject(s) - hepatocellular carcinoma , medicine , intrahepatic cholangiocarcinoma , kras , univariate analysis , gastroenterology , stage (stratigraphy) , metastasis , carcinoma , histology , pathology , oncology , multivariate analysis , cancer , biology , colorectal cancer , paleontology
Aim Cholangiolocellular carcinoma (CLC) is classified as a subtype of combined hepatocellular cholangiocarcinoma with stem‐cell features (CHC‐SC) in the latest World Health Organization classification. This subclassification of CHC‐SCs is controversial and the relevance of such classification is unclear. Methods We analyzed a series of CHC‐SCs and intrahepatic cholangiocarcinoma (iCCA) to clarify the clinicopathological features and mutational status of each tumor. Results Background liver disease, fibrosis stage, microvascular invasion, nodal metastasis, and IDH1/2 mutation status were associated with their histology. Compared with the intermediate cell subtype of CHC‐SC (CHCs‐SC‐int), CLCs were less frequently associated with chronic viral hepatitis, and showed lower levels of serum alpha‐fetoprotein. Compared with iCCAs, CLCs showed lower levels of serum carbohydrate antigen 19‐9 (CA19‐9) and a lower frequency of expression of S100P. Patients with iCCA showed worse overall survival than those with CLC or CHC‐SC‐int. In patients with iCCA, CLC, or CHC‐SC‐int, a histology of iCCA, microvascular invasion, and serum CA19‐9 value of >100 U/mL were significant poor prognostic factors for overall survival in univariate analysis. Multivariate analysis showed that a high serum CA19‐9 value was an independent poor prognostic factor for overall survival. Conclusions Patients with CLC are likely to have a different etiology and mutational background from those with CHC‐SC‐int. Their clinicopathological manifestations are also different from those with classic iCCA. Our results suggest that CLC might be a distinct entity among primary liver carcinomas.