Evidence map›Paper›PMID 36104536›Full record

SynthesisModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2022

Validity of a two-antibody testing algorithm for mismatch repair deficiency testing in cancer; a systematic literature review and meta-analysis.

K T S Aiyer, T Doeleman, N A Ryan, M Nielsen, E J Crosbie, V T H B M Smit, H Morreau, J J Goeman, T Bosse

Open access · hybridAbstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Article
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  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Molecular pathology in breast disease: diagnostic, prognostic, and therapeutic tools.Virchows Archiv : an international journal of pathology · 2024
    Review
  14. Molecular pathological classification of colorectal cancer-an update.Virchows Archiv : an international journal of pathology · 2024
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

K T S AiyerDepartment of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, The Netherlands.
T DoelemanDepartment of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, The Netherlands.
N A RyanDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, UK.ORCID 0000-0003-3117-3257
M NielsenDepartment of Clinical Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, The Netherlands.
E J CrosbieDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, UK.ORCID 0000-0003-0284-8630
V T H B M SmitDepartment of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, The Netherlands.
H MorreauDepartment of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, The Netherlands.
J J GoemanDepartment of Biomedical Data Sciences, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, The Netherlands.
T BosseDepartment of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, The Netherlands. t.bosse@lumc.nl.
Leiden University Medical Center · NLManchester Academic Health Science Centre · GBUniversity of Manchester · GB

Funding

Department of Health IS-BRC-1215-20007Department of Health NIHR300650
6 · The paper itself

Abstract

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.

Indexed as

Colorectal NeoplasmsDNA-Binding ProteinsAlgorithmsBiomarkers, TumorBrain NeoplasmsDNA Mismatch RepairHumansMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinNeoplastic Syndromes, HereditaryBiomarkers, TumorDNA-Binding ProteinsMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 Protein

Identifiers

PMID36104536
PMCPMC9708570
OpenAlexW4295901035

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.