Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2025 Dec;21(1):2471226.
doi: 10.1080/21645515.2025.2471226. Epub 2025 Feb 25.

Immunotherapy-induced microsatellite instability status shift in recurrent perihilar cholangiocarcinoma: A case report

Hailing Yu  1 , Tan Deng  1 , Hongbing Liu  2
Affiliations
Case Reports

Immunotherapy-induced microsatellite instability status shift in recurrent perihilar cholangiocarcinoma: A case report

Hailing Yu et al. Hum Vaccin Immunother. 2025 Dec.

Abstract

Immunotherapy revolutionized the treatment of biliary tract tumors and tumors with high microsatellite instability (MSI-H). This paper reports a 52-year-old woman with recurrent perihilar cholangiocarcinoma. The tumor was initially microsatellite stable (MSS) and proficient mismatch repair (pMMR) but shifted to MSI-H and deficient mismatch repair (dMMR) after combined immunotherapy. Following laparoscopic radical resection for jaundice, stage IV recurrence was diagnosed. Genetic testing revealed the MSS status. Subsequent treatment with camrelizumab and lenvatinib led to a partial response. Ovarian metastases, removed due to abdominal symptoms, exhibited dMMR and MSI-H. The mismatch in MSI status between the primary tumor and metastases suggests tumor heterogeneity and the influence of spatial or temporal factors. This shift can have important clinical significance since MSI-H is associated with significant responses to immune checkpoint inhibitors. MSI-H should be systematically tested in tumors and metastases to personalize treatments. MSI heterogeneity is not only rare but potentially has implications for treatment personalization and prognosis in patients with cholangiocarcinoma. This case highlights the dynamic changes in tumor characteristics during immunotherapy.

Keywords: Recurrent perihilar cholangiocarcinoma; case report; combined immunotherapy; microsatellite instability status; tumor heterogeneity.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Positron emission tomography (pet)-computed tomography (CT) assessment of dynamic change of recurrent hepatic lesion during combined immunotherapy. (a) Diagram of the recurrent hepatic foci at the first surgical recurrence (2020-10-21). (b) The latest CT imaging evaluation after combined treatment (March 09, 2023). The red arrows show the cancer lesions.
Figure 2.
Figure 2.
Immunohistochemistry for deficient mismatch repair (dMMR) markers from March 2022 showing (a) MLH1 (-), (b) MSH2 (++), (c) MSH6 (++), and (d) PMS2 (-). Magnification: 200 × .
Figure 3.
Figure 3.
Line chart of the changes in CA199 from 2020 to 2021, along with the clinical events.
See this image and copyright information in PMC

References

    1. Liu L, Zhang Z, Zhou Y, Pu Y, Liu D, Tian J.. Brain symmetry index predicts 3-month mortality in patients with acute large hemispheric infarction. Medicine. 2022;101(47):e31620. doi:10.1097/MD.0000000000031620. - DOI - PMC - PubMed
    1. Chun YS, Javle M. Systemic and adjuvant therapies for intrahepatic cholangiocarcinoma. Cancer Control: J Moffitt Cancer Cent. 2017;24(3):1073274817729241. doi:10.1177/1073274817729241. - DOI - PMC - PubMed
    1. Taieb J, Svrcek M, Cohen R, Basile D, Tougeron D, Phelip J-M. Deficient mismatch repair/microsatellite unstable colorectal cancer: diagnosis, prognosis and treatment. Eur J Cancer. 2022;175:136–6. doi:10.1016/j.ejca.2022.07.020. - DOI - PubMed
    1. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol: Off J Am Soc Clin Oncol. 2005;23(3):609–618. doi:10.1200/JCO.2005.01.086. - DOI - PubMed
    1. Greco L, Rubbino F, Dal Buono A, Laghi L. Microsatellite instability and immune response: from microenvironment features to therapeutic actionability—lessons from colorectal cancer. Genes (Basel). 2023;14(6):1169. doi:10.3390/genes14061169. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources