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MMR profile and microsatellite instability status in colorectal mucinous adenocarcinoma with synchronous metastasis: a new clue for the clinical practice
  1. Paola Parente1,
  2. Umberto Malapelle2,
  3. Valentina Angerilli3,
  4. Mariangela Balistreri4,
  5. Sara Lonardi5,
  6. Salvatore Pucciarelli6,
  7. Caterina De Luca2,
  8. Francesco Pepe2,
  9. Gianluca Russo2,
  10. Elena Vigliar2,
  11. Angela Danza1,
  12. Fabio Scaramuzzi1,
  13. Giancarlo Troncone2,
  14. Paolo Graziano1,
  15. Matteo Fassan3,7
  1. 1Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
  2. 2Department of Public Health, University of Naples Federico II, Naples (NA), Italy
  3. 3Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua (PD), Italy
  4. 4Surgical Pathology Unit, University Hospital of Padua, Padua (PD), Italy
  5. 5Oncology Unit 3, Veneto Institute of Oncology, IOV-IRCCS, Castelfranco Veneto (TV), Italy
  6. 6Department of Surgical Oncology and Gastroenterology Sciences, First Surgical Clinic, University of Padua, Padua (PD), Italy
  7. 7Veneto Institute of Oncology, IOV-IRCCS, Padua (PD), Italy
  1. Correspondence to Dr Matteo Fassan, Department of Medicine, University of Padua, Padova, Italy; matteo.fassan{at}unipd.it

Abstract

Aims Mucinous adenocarcinoma (MA) is associated with a high frequency of microsatellite instability (MSI). In the metastatic setting, it is crucial to establish mismatch repair (MMR) and/or MSI status. However, genetic heterogeneity between primary tumour and synchronous metastasis and the diagnostic accuracy of the assay may hamper the MMR/MSI status evaluation.

Methods In this study, we assessed the concordance rate of the MMR/MSI status between primary tumour and paired synchronous metastasis of 25 MAs. MMR status was evaluated by immunohistochemistry (IHC), while MSI status was evaluated by using three different molecular approaches: microfluidic electrophoresis of PCR products (TapeStation 4200 platform), full-closed RTqPCR system (Idylla system) and multiplex amplification with fluorescent primers and subsequent DNA fragment analysis on an automated sequencer (Titano MSI test).

Results The concordance rate between primary MA and metastasis was 21/21 (100%), 23/25 (92.0%), 23/25 (92.0%) and 21/25 (84%) by using IHC, Idylla system, Titano MSI test and TapeStation 4200 system. All the four methods used in our study displayed high concordant rate, ranging from 91.0% (IHC vs Tapestation 4200 platform) to 98.0% (IHC vs Titano).

Conclusions Several methodologies are frequently adopted in routine practice to successfully perform MMR/MSI status analysis. The most relevant issues related to MMR/MSI status analysis in MAs concern with low percentage of neoplastic cell and abundant mucine that may affect the molecular analysis. Thus, it might be useful to acquire both primary and metastatic sample to evaluate the MMR/MSI status by integrating IHC evaluation and molecular methodologies to successfully perform molecular profiling for MA patients.

  • colorectal neoplasms
  • immunohistochemistry
  • medical oncology

Data availability statement

All data relevant to the study are included in the article.

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Data availability statement

All data relevant to the study are included in the article.

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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors Conceptualisation: PP, UM and MF; methodology: PP, UM, VA, MB, CDL, FP, GR, EV, AD, FS; formal analysis, PP, UM, MB, CDL, FP, GR, EV, AD, FS and MF; resources: PP, UM, SL, SP, GT, PG and MF; data curation, PP, UM,and MF; writing—original draft preparation, PP, UM, VA and MF; writing—review and editing, SL, GT and PG; supervision, GT, PG and MF; funding acquisition, GT, PG and MF; guarantor: MF. All authors read and agreed to the published version of the manuscript.

  • Funding MF is supported by a grant from the Italian Health Ministry/Veneto region research programme NET-2016-02363853 and AIRC 5 per mille 2019 (ID. 22 759 programme).

  • Competing interests UM has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, unrelated to the current work. GT reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work. SL reports personal fees (as speaker bureau or advisor) from Amgen, Merck Serono, Lilly, Astra Zeneca, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb, Servier, MSD, Roche, Bristol-Myers Squibb, Pierre-Fabre, GSK and received research grants from Amgen, Merck Serono, Bayer, Roche, Lilly, Astra Zeneca, Bristol-Myers Squibb, unrelated to the current work. MF reports personal fees (as speaker bureau or advisor) from Roche, MSD, GSK, Astellas Pharma, Diaceutics and received research grants from Astellas Pharma, QED therapeutics and macrophage pharma, unrelated to the current work.

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

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