Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer

A Guyot D'Asnières De Salins; G Tachon; R Cohen; L Karayan-Tapon; A Junca; E Frouin; J Godet; C Evrard; V Randrian; A Duval; M Svrcek; O Lascols; S Vignot; F Coulet; T André; J-F Fléjou; P Cervera; D Tougeron

doi:10.1016/j.esmoop.2021.100120

Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer

ESMO Open. 2021 Jun;6(3):100120. doi: 10.1016/j.esmoop.2021.100120. Epub 2021 Apr 28.

Authors

A Guyot D'Asnières De Salins¹, G Tachon², R Cohen³, L Karayan-Tapon², A Junca⁴, E Frouin⁴, J Godet⁴, C Evrard⁵, V Randrian⁶, A Duval⁷, M Svrcek⁸, O Lascols⁷, S Vignot³, F Coulet⁹, T André¹⁰, J-F Fléjou⁸, P Cervera⁸, D Tougeron¹¹

Affiliations

¹ Gastroenterology Department, Poitiers University Hospital, Poitiers, France.
² Faculty of Medicine, University of Poitiers, Poitiers, France; INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, Poitiers, France; Cancer Biology Department, Poitiers University Hospital, Poitiers, France.
³ Sorbonne University, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, Paris, France.
⁴ Pathology Department, Poitiers University Hospital, Poitiers, France.
⁵ Medical Oncology Department, Poitiers University Hospital, Poitiers, France.
⁶ Gastroenterology Department, Poitiers University Hospital, Poitiers, France; Faculty of Medicine, University of Poitiers, Poitiers, France.
⁷ Sorbonne University, INSERM, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France.
⁸ Sorbonne University, INSERM, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France; Sorbonne University, Department of Pathology, Saint-Antoine Hospital, AP-HP, Paris, France.
⁹ Department of Genetics, Pitié Salpétrière Hospital, AP-HP and Sorbonne University, Paris, France.
¹⁰ Sorbonne University, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, Paris, France; Sorbonne University, INSERM, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France.
¹¹ Gastroenterology Department, Poitiers University Hospital, Poitiers, France; Faculty of Medicine, University of Poitiers, Poitiers, France; Medical Oncology Department, Poitiers University Hospital, Poitiers, France. Electronic address: davidtougeron@hotmail.fr.

Abstract

Background: DNA mismatch repair system deficiency (dMMR) is found in 15% of colorectal cancers (CRCs). Two methods are used to determine dMMR, immunohistochemistry (IHC) of MMR proteins and molecular testing of microsatellite instability (MSI). Only studies with a low number of patients have reported rates of discordance between these two methods, ranging from 1% to 10%.

Materials and methods: Overall, 3228 consecutive patients with CRCs from two centers were included. Molecular testing was carried out using the Pentaplex panel and IHC evaluated four (MLH1, MSH2, MSH6, and PMS2; cohort 1; n = 1085) or two MMR proteins (MLH1 and MSH2; cohort 2; n = 2143). The primary endpoint was the rate of discordance between MSI and MMR IHC tests.

Results: Fifty-one discordant cases (1.6%) were initially observed. Twenty-nine out of 51 discordant cases were related to IHC misclassifications. In cohort 1, after re-reading IHC and/or carrying out new IHC, 16 discordant cases were reclassified as nondiscordant. In cohort 2, after the addition of MSH6/PMS2 IHC and re-examination, 13 were reclassified as nondiscordant. In addition, 10 misclassifications of molecular tests were identified. Finally, only 12 discordant cases (0.4%) remained: 5 were proficient MMR/MSI and 7 were dMMR/microsatellite stable.

Conclusions: Our study confirmed the high degree of concordance between MSI and MMR IHC tests. Discordant cases must be reviewed, and if needed, tests must be repeated and analyzed by an expert team.

Keywords: colorectal cancer; deficient mismatch repair; immunohistochemistry; microsatellite instability; molecular biology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms* / diagnosis
Colorectal Neoplasms* / genetics
DNA Mismatch Repair / genetics
Humans
Immunochemistry
Microsatellite Instability*
Molecular Diagnostic Techniques