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. 2019 May 8;14(1):36.
doi: 10.1186/s13000-019-0813-5.

Low frequency of mismatch repair deficiency in gallbladder cancer

Benjamin Goeppert  1   2 , Stephanie Roessler  3   4 , Marcus Renner  3 , Moritz Loeffler  3 , Stephan Singer  3 , Melina Rausch  3 , Thomas Albrecht  3   4 , Arianeb Mehrabi  4   5 , Monika Nadja Vogel  6 , Anita Pathil  7 , Elena Czink  4   8 , Bruno Köhler  4   8 , Christoph Springfeld  4   8 , Christian Rupp  4   8 , Karl Heinz Weiss  4   7 , Peter Schirmacher  3   4 , Magnus von Knebel Doeberitz  9 , Matthias Kloor  9
Affiliations

Low frequency of mismatch repair deficiency in gallbladder cancer

Benjamin Goeppert et al. Diagn Pathol. .

Abstract

Background: DNA mismatch repair (MMR) deficiency is a major pathway of genomic instability in cancer. It leads to the accumulation of numerous mutations predominantly at microsatellite sequences, a phenotype known as microsatellite instability (MSI). MSI tumors have a distinct clinical behavior and commonly respond well to immune checkpoint blockade, irrespective of their origin. Data about the prevalence of MSI among gallbladder cancer (GBC) have been conflicting. We here analyzed a well-characterized cohort of 69 Western-world GBCs.

Methods: We analyzed the mononucleotide MSI marker panel consisting of BAT25, BAT26, and CAT25 to determine the prevalence of MMR deficiency-induced MSI.

Results: MSI was detected in 1/69 (1.4%) of analyzed GBCs. The detected MSI GBC had a classical histomorphology, i.e. of acinar/tubular/glandular pancreatobiliary phenotype, and showed nuclear expression of all four MMR proteins MLH1, MSH2, MSH6, and PMS2. The MSI GBC patient showed a prolonged overall survival, despite having a high tumor stage at diagnosis. The patient had no known background or family history indicative of Lynch syndrome.

Conclusions: Even though the overall number of MSI tumors is low in GBC, the potentially therapeutic benefit of checkpoint blockade in the respective patients may justify MSI analysis of GBC.

Keywords: Biliary tract cancer; DNA mismatch repair deficiency; Gallbladder cancer; Microsatellite instability.

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Conflict of interest statement

Ethics approval and consent to participate

The use of tissue specimens for this study was approved by the Ethics Committee of the Medical Faculty, University Heidelberg (206/05).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Results of microsatellite instability analysis. Peak patterns of the MSI tumor analyzed by the GeneMapper Software (version 5, Applied Biosystems) show aberrant peak profiles indicative of MSI in all 4 tested mononucleotide markers. Highest peaks in MSI profiles obtained from normal tissue are marked by asterisks (upper panel). Aberrant peaks detected in tumor tissue are marked by red arrows (lower panel)
Fig. 2
Fig. 2
Histology and immunohistochemistry of the detected MSI gallbladder carcinoma. a: Hematoxylin & Eosin (HE) staining of a full-slide section of the detected MSI GBC shows a typical ductal morphology of pancreatobiliary subtype (representative atypical neoplastic ducts are indicated by arrows, original magnification: 20x). b-e: Immunohistochemistry of MMR proteins showed retained nuclear signals in the neoplastic epithelia (MLH1, PMS2, MSH2, and MSH6; original magnification: 100x)
See this image and copyright information in PMC

References

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