Microsatellite Instability Occurs Rarely in Patients with Cholangiocarcinoma: A Retrospective Study from a German Tertiary Care Hospital.

Ria Winkelmann,Andreas Schnitzbauer,Sylvia Hartmann,Stefan Zeuzem,Martin Hansmann,Jan Peveling-Oberhag,Dirk Walter,Markus Schneider

doi:10.3390/ijms19051421

Abstract

Immune-modulating therapy is a promising therapy for patients with cholangiocarcinoma (CCA). Microsatellite instability (MSI) might be a favorable predictor for treatment response, but comprehensive data on the prevalence of MSI in CCA are missing. The aim of the current study was to determine the prevalence of MSI in a German tertiary care hospital. Formalin-fixed paraffin-embedded tissue samples, obtained in the study period from 2007 to 2015 from patients with CCA undergoing surgical resection with curative intention at Johann Wolfgang Goethe University hospital, were examined. All samples were investigated immunohistochemically for the presence of MSI (expression of MLH1, PMS2, MSH2, and MSH6) as well as by pentaplex polymerase chain reaction for five quasimonomorphic mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-22, and NR-24). In total, 102 patients were included, presenting intrahepatic (n = 35, 34.3%), perihilar (n = 42, 41.2%), and distal CCA (n = 25, 24.5%). In the immunohistochemical analysis, no loss of expression of DNA repair enzymes was observed. In the PCR-based analysis, one out of 102 patients was found to be MSI-high and one out of 102 was found to be MSI-low. Thus, MSI seems to appear rarely in CCA in Germany. This should be considered when planning immune-modulating therapy trials for patients with CCA.

Highlights

Cholangiocarcinoma (CCA) is a gastrointestinal neoplasia which derives from the biliary epithelium or peribiliary glands within the biliary tree
We provide data on prevalence of Microsatellite instability (MSI) in the so far largest cohort of western patients including all subtypes of CCA
Because of the emerging role of MSI in personalized cancer therapy, MSI prevalence was increasingly investigated in recent years

Summary

Introduction

Cholangiocarcinoma (CCA) is a gastrointestinal neoplasia which derives from the biliary epithelium or peribiliary glands within the biliary tree. It is subdivided into intrahepatic (iCCA) and extrahepatic perihilar (pCCA) and distal cholangiocarcinoma (dCCA). A new promising approach in cancer therapy has evolved with the emergence of immune-modulating monoclonal antibodies. These agents focus on receptors or ligands of effector cells as targets for cancer immunotherapy by inhibiting immune check points such as the programmed cell death protein 1 (PD-1, CD279) and its ligand (PD-L1) or the protein receptor CTLA4 (CD152). Promising results have been shown for various other solid tumors and hematologic malignancies [7]

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