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Original research
Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications
  1. Claudio Luchini1,
  2. Lodewijk A A Brosens2,3,
  3. Laura D Wood4,
  4. Deyali Chatterjee5,
  5. Jae Il Shin6,
  6. Concetta Sciammarella1,
  7. Giulia Fiadone1,
  8. Giuseppe Malleo7,
  9. Roberto Salvia7,
  10. Valentyna Kryklyva3,
  11. Maria L Piredda1,
  12. Liang Cheng8,
  13. Rita T Lawlor9,
  14. Volkan Adsay10,
  15. Aldo Scarpa11
  1. 1 Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
  2. 2 Pathology, University Medical Center, Utrecht, The Netherlands
  3. 3 Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
  4. 4 Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
  5. 5 Pathology and Immunology, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA
  6. 6 Pediatrics, Yonsei University College of Medicine, Seoul, The Republic of Korea
  7. 7 General and Pancreatic Surgery, University and Hospital Trust of Verona, Verona, Italy
  8. 8 Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
  9. 9 ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy
  10. 10 Pathology, Koç University Hospital, Istanbul, Turkey
  11. 11 ARC-Net Research Center and Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
  1. Correspondence to Professor Claudio Luchini, Diagnostics and Public Health, University and Hospital Trust of Verona, Verona 37134, Italy; claudio.luchini{at}


Objective Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC).

Design PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project).

Results Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%–2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a KRAS/TP53 wild-type molecular background (p<0.01), with more common JAK genes mutations. Data on survival are still unclear.

Conclusion PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.

  • microsatellite instability
  • pancreatic cancer
  • immunotherapy

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  • Contributors CL and AS conceived the study. CL, LAAB, RTL, VA and AS: study design. CL, AS and RTL: data extraction and elaboration. CL: statistical analysis. All authors: data interpretation and discussion. CL and AS: manuscript writing. All authors: manuscript editing and final approval.

  • Funding This study is supported by Associazione Italiana Ricerca sul Cancro (AIRC 5x1000 n. 12182) and Fondazione Cariverona: Oncology Biobank Project 'Antonio Schiavi' (prot. 203885/2017). VK is supported by the Dutch Cancer Society (KWF grant 2016, 10289).

  • Competing interests LDW has been a paid consultant for PGDx (Personal Genome Diagnostics, Baltimore, MD, USA). CL has been a paid expert-consultant on microsatellite instability for BioScience Communications (New York, New York, USA).

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Data are available in a public, open access repository.

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