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Updated: Jun 18, 2025
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Published on: January 17, 2025
Pathologic and Molecular Features of Perihilar Cholangiocarcinoma Based on U-P Point Division
Ying Xiao1, Qijia Zhang1, Canhong Xiang1
1From the Departments of Pathology (Xiao, Yang, Li, Yin), Liver ICU (Zhang), and Hepatopancreatobiliary Surgery (Xiang), Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Context.—:
The Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines propose a classification scheme that differs from the Union for International Cancer Control (UICC) system, in which the anatomic U-P point is the boundary between intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma (PCC).
Objective.—:
To investigate whether this classification system improves clinicopathologic and genomic differentiation.
Design.—:
Fifty-eight PCC cases defined by the UICC system were collected and classified into intrahepatic PCC (IPCC) and extrahepatic PCC (EPCC) categories using U-P point division. They were analyzed by next-generation sequencing using a panel that targeted 425 cancer-related genes.
Results.—:
The IPCC group exhibited a significantly larger tumor size compared with the EPCC group (4.67 ± 2.44 cm versus 2.50 ± 0.91 cm, P = .002). The mutation frequency of the KRAS proto-oncogene, GTPase (KRAS) Q61 was also significantly higher in the IPCC group than in the EPCC group (16.7% versus 0.0%, P = .03). There were no statistically significant differences in other pathologic features or genomic characteristics, including tumor mutation burden and microsatellite instability. Significant differences in gene mutation rates, such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA; 0.0% versus 15.8%, P = .01) and tumor protein p53 (TP53; 34.5% versus 63.2%, P = .04), were observed between PCC and adjacent biliary tract cancers.
Conclusions.—:
This study offers valuable insight into the clinicopathologic and genomic features of PCC. It is proposed that the U-P point division may have limited potential to refine the characterization of PCC regarding these features, and that the UICC classification system can readily demonstrate the molecular specificity of PCC.
