Validity of a two-antibody testing algorithm for mismatch repair deficiency testing in cancer; a systematic literature review and meta-analysis.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
02
02
2022
accepted:
04
08
2022
revised:
01
08
2022
pubmed:
15
9
2022
medline:
2
12
2022
entrez:
14
9
2022
Statut:
ppublish
Résumé
Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been approved as a pan-cancer predictive biomarker for checkpoint inhibitor therapy, leading to a vast increase in the use of MMR IHC in clinical practice. We explored whether immunohistochemical staining with PMS2 and MSH6 can be used as a reliable substitute. This two-antibody testing algorithm has the benefit of saving tissue, cutting costs and saving time. PubMed, Embase and Cochrane library were systematically searched for articles reporting on MMR IHC. The weighed percentage of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was analyzed using a random effects model meta-analysis in R. The search yielded 1704 unique citations, of which 131 studies were included, describing 9014 patients. A weighed percentage of 1.1% (95% CI 0.53-18.87, I = 87%) of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was observed. In the six articles with the main aim of investigating the two-antibody testing algorithm all MMRd cases were detected with the two-antibody testing algorithm, there were no cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone. This high detection rate of MMRd of the two-antibody testing algorithm supports its use in clinical practice by specialized pathologists. Staining of all four antibodies should remain the standard in cases with equivocal results of the two-antibody testing algorithm. Finally, educational sessions in which staining pattern pitfalls are discussed will continue to be important.
Identifiants
pubmed: 36104536
doi: 10.1038/s41379-022-01149-w
pii: S0893-3952(22)05489-8
pmc: PMC9708570
doi:
Substances chimiques
Mismatch Repair Endonuclease PMS2
EC 3.6.1.3
MutL Protein Homolog 1
EC 3.6.1.3
MutS Homolog 2 Protein
EC 3.6.1.3
DNA-Binding Proteins
0
Biomarkers, Tumor
0
Types de publication
Systematic Review
Meta-Analysis
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1775-1783Subventions
Organisme : Department of Health
ID : NIHR300650
Pays : United Kingdom
Organisme : Department of Health
ID : IS-BRC-1215-20007
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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