Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612782
Poster Visit Session IV Tumors, Liver Surgery and Transplantation – Saturday, January 27, 2018, 8:30am – 9:15am, Foyer area West Wing
Georg Thieme Verlag KG Stuttgart · New York

Low Frequency of Mismatch Repair Deficiency in a Large Cohort of Non-liver fluke associated Cholangiocarcinomas

B Goeppert
1   University Hospital, Institute of Pathology, Heidelberg
,
S Roessler
1   University Hospital, Institute of Pathology, Heidelberg
,
M Renner
1   University Hospital, Institute of Pathology, Heidelberg
,
S Singer
1   University Hospital, Institute of Pathology, Heidelberg
,
A Mehrabi
2   University Hospital, Department of General Visceral and Transplantation Surgery, Heidelberg
,
A Pathil
3   University Hospital, Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg
,
E Czink
4   University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg
,
B Köhler
4   University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg
,
C Springfeld
4   University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg
,
J Pfeiffenberger
3   University Hospital, Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg
,
C Rupp
3   University Hospital, Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg
,
K Weiss
3   University Hospital, Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg
,
P Schirmacher
1   University Hospital, Institute of Pathology, Heidelberg
,
M Knebel Doeberitz
5   University Hospital, Department of Applied Tumor Biology, Institute of Pathology, Heidelberg
,
M Kloor
5   University Hospital, Department of Applied Tumor Biology, Institute of Pathology, Heidelberg
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

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Question:

A major molecular pathway of genetic instability in cancer is DNA mismatch repair (MMR) deficiency. MMR deficiency leads to the accumulation of numerous mutations at repetitive DNA sequence stretches (microsatellites), a phenotype known as high-level microsatellite instability (MSI-H). In colorectal cancer, MSI-H tumors show a clinical behavior different from microsatellite-stable (MSS) tumors. Data about the prevalence of MSI-H among cholangiocarcinoma (CCA) are conflicting, and the clinical relevance of MSI-H in this tumor type is largely unknown. MSI analysis has recently gained increasing clinical significance, because MSI-H is associated with responsiveness towards immune checkpoint blockade. We here aimed to analyze a comprehensive and well-characterized cohort of CCAs including all subtypes.

Methods:

This series comprised 308 Western world, non-liver fluke-associated CCAs and included intrahepatic (n = 159) and extrahepatic (perihilar: n = 106; distal: n = 43) CCAs. We analyzed the mononucleotide MSI marker panel consisting of BAT25, BAT26, and CAT25 to determine the prevalence of MMR deficiency-induced MSI-H and correlated the results with clinicopathological variables including patients” survival data.

Results:

MSI-H was detected in 4/308 (1.3%) cases of CCA patients. Patients affected by MSI-H CCA had mostly an atypical histomorphology, i.e. not the classical acinar/tubular/glandular/NOS pancreatobiliary type (p = 0.004) but a papillary, mucinous or solid growth pattern, show a better overall survival, and were of younger age, although in none of these patients, a background of Lynch syndrome has been known.

Conclusions:

Even though the overall number of MSI-H tumors is low in CCA, the potentially dramatic therapeutic benefit of checkpoint blockade in the respective patients justifies MSI analysis of CCA, particularly those of younger patient's age and displaying an atypical histomorphology.