REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1653534
This article is part of the Research TopicIntrahepatic Cholangiocarcinoma: Emerging Insights from Pathobiology to Clinical Translation – Innovative Strategies, Challenges, and OpportunitiesView all 8 articles
Immunohistochemistry in intrahepatic cholangiocarcinoma: histological subtyping and drug selection
Provisionally accepted
- 1Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
- 2Changhai Hospital, Shanghai, China
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Introduction: Since the release of the World Health Organization (WHO) Classification of Tumours-Digestive System Tumours in 2019, the pathology of intrahepatic cholangiocarcinoma (iCCA) has entered an era of integrated diagnosis, encompassing gross classification, histological subtyping, as well as drug molecular target screening. Substantial evidence indicates that the histological subtypes of iCCA are significantly associated with the detection frequency of molecular targets relevant to the targeted therapy and immunotherapy. Through rational immunohistochemistry profiling, patients with iCCA can be precisely diagnosed and individually managed. Methods: A thorough literature search was conducted using terms pertinent to the pathological diagnosis, histological subtyping, targeted therapy, and immunotherapy of iCCA. The content related to immunohistochemistry was summarized. Results: In the first part, we summarize the immunohistochemical markers for the histological subtype of iCCA (e.g., large duct type iCCA, small duct type iCCA), with a particular emphasis on their percentage of positive cases, expression location, and association with prognosis. Subsequently, a summary of the immunohistochemical markers for targeted therapy and immunotherapy of iCCA is performed, focusing on the consistency between immunohistochemistry and molecular detection, optimal clone, and prognostic significance. Conclusions: This review summarizes the critical role of immunohistochemistry in the pathological diagnosis of iCCA. It is noted that any diagnosis must be made by integrating comprehensive information. A pathological diagnosis merely based on immunohistochemical results is unreasonable. The development of subtype-specific and drug-targeted antibodies holds promise for refining iCCA precise diagnosis and therapeutic stratification.
Keywords: Large duct type, Small duct type, Cholangiolocarcinoma, iCCA with ductal plate malformation pattern, target therapy, Immunotherapy, Molecular pathology, IHC
Received: 25 Jun 2025; Accepted: 19 Sep 2025.
Copyright: © 2025 Wang, He, Cong and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Miao-Xia He, hmm26@163.com
Wen-Ming Cong, wmcong@smmu.edu.cn
Hui Dong, huidongwh@126.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.