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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2512 - Assessment of local clinical practice for testing of mismatch repair deficiency in metastatic colorectal cancer: The need for new diagnostic guidelines prior to immunotherapy


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Pathology/Molecular Biology

Tumour Site

Colon and Rectal Cancer


Romain Cohen


Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281


R. Cohen1, E. Hain2, O. Buhard2, A. Guilloux3, A. Bardier4, R. Kaci5, P. Bertheau6, F. Renaud7, F. Bibeau8, J. Fléjou9, T. André1, M. Svrcek9, A. Duval2

Author affiliations

  • 1 Medical Oncology, Sorbonne Université, AP-HP, hôpital Saint-Antoine, 75571 - Paris/FR
  • 2 Centre De Recherche Saint-antoine, Equipe Instabilité Des Microsatellites Et Cancer, Equipe Labellisée Par La Ligue Nationale Contre Le Cancer, Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, 75012 - Paris/FR
  • 3 Umr 8071, Evry University, 91037 - Évry/FR
  • 4 Pathology, AP-HP, hôpital Pitié Salpétrière, 75013 - Paris/FR
  • 5 Pathology, AP-HP, hôpital Lariboisière, 75010 - Paris/FR
  • 6 Pathology, AP-HP, hôpital Saint-Louis, 75010 - Paris/FR
  • 7 Pathology, CHU Lille, 59000 - Lille/FR
  • 8 Service D'anatomie Pathologique, CHU de Caen, 14033 - Caen/FR
  • 9 Pathology, Sorbonne Université, AP-HP, hôpital Saint-Antoine, 75012 - Paris/FR


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Abstract 2512


Immune checkpoint inhibitors (ICKi) have been approved for patients with metastatic colorectal cancer (mCRC) displaying MSI/dMMR (microsatellite instability, defective mismatch repair). We aimed to evaluate the accuracy of standard immunohistochemistry and PCR methods for the detection of MSI/dMMR in mCRC in routine clinical practice.


The study was performed on a multicenter retrospective cohort of mCRCs previously determined as MSI and/or dMMR by local assessment and on a prospective, single center cohort of patients included in ICKi trials based on positive MSI and/or dMMR status previously determined by the originating institutes. We re-assessed dMMR and MSI status in our specialized diagnostic center using immunohistochemistry (antibodies directed against MLH1, MSH2, MSH6 and PMS2), and pentaplex PCR (BAT-25, BAT-26, NR-21, NR-24 and NR-27). The positive predictive value (PPV) of local assessment was the primary objective of the study. Detection rate (i.e. conclusive result) and sensitivity of immunohistochemistry and PCR by central review were evaluated.


Nine false-positives (9.8%) were found in the retrospective cohort (N = 92). These were initially diagnosed as MSI and/or dMMR by the originating institute but were reclassified as MMR proficient /microsatellite stable in our laboratory (PPV=90.2%; 95%CI, 82.2-95.0). The PPV in the prospective cohort (N = 39) was 92.3% (95%CI, 79.0-98.1), with the 3 false-positive patients experiencing progressive disease with ICKi treatment. Amongst the 119 true-positive mCRCs, the detection rate and sensitivity were respectively 100% and 95.8% for immunohistochemistry, while for pentaplex PCR these were 81.5% and 95.9%. Only the combination of immunohistochemistry and pentaplex PCR methods resulted in 100% detection rate and 100% sensitivity.


Local assessment of MSI/dMMR status in mCRC resulted in misdiagnosis of 9.1% of cases as false positive and subsequently incorrect treatment with ICKi. We recommend new guidelines that mandate dual testing of mCRC samples in experienced diagnostic centers using both PCR and immunohistochemistry.

Clinical trial identification

Legal entity responsible for the study



ARCAD Foundation, Institut National du Cancer, Ligue Contre Le Cancer.

Editorial Acknowledgement


T. André: Consultancy: Bristol-Myers Squibb, Fees: Merck. All other authors have declared no conflicts of interest.

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