Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency.

Autor: Makino K; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Ishii T; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Takeda H; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Saito Y; Laboratory of Bioengineering, Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto, Japan., Fujiwara Y; Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan., Fujimoto M; Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Ito T; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Wakama S; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Kumagai K; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Munekage F; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Horie H; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Tomofuji K; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Oshima Y; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Uebayashi EY; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Kawai T; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Department of Surgery, Medical Research Institute Kitano Hospital, Osaka, Japan., Ogiso S; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Fukumitsu K; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Takai A; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Seno H; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Hatano E; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2024 May; Vol. 263 (1), pp. 32-46. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1002/path.6257
Abstrakt: Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.
(© 2024 The Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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