Aims: Traditionally, mismatch repair (MMR) status is determined by a panel of four antibodies (MLH1, PMS2, MSH2, MSH6). If all proteins are retained, cases are MMR proficient (pMMR), while loss of one or more proteins is indicative of MMR deficiency (dMMR). This approach has been challenged in favour of a two-antibody approach, using PMS2 and MSH6 as a first screening. Their retainment is deemed sufficient to declare cases pMMR. In this study we aim to verify the validity of the two-antibody approach.
Methods And Results: We performed a nationwide study in colorectal cancer (CRC) and endometrial cancer (EC) diagnosed between 2016 and 2023, including 47,657 patients to evaluate the two-antibody approach. In 0.17% and 0.4% of cases of CRC and EC, respectively, dMMR cases would be missed with the two-antibody approach. Subgroup analyses pointed towards slightly increased miss rates in younger patients (under the age of 50 years) in both groups and identified special subtypes (signet ring cell carcinoma, medullary carcinoma, and mucinous carcinoma in CRC and clear cell carcinoma in EC) with increased miss rates. For these specific subgroups, a low threshold should be used for further testing. In case of ambiguous or heterogeneous staining patterns, four antibodies should be used.
Conclusion: In general, the application of a two-antibody MMR testing strategy does not lead to considerable failure of dMMR identification and saves costs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/his.15236 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Simplifying Mismatch Repair Deficiency Screening in Endometrial Adenocarcinoma: Immunohistochemistry with Two-Antibody Panel (PMS2 and MSH6).
Asian Pac J Cancer Prev
October 2024
Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Article Synopsis
- The study focuses on comparing a simplified two-antibody method (PMS2 and MSH6) against a traditional four-antibody method for diagnosing mismatch repair deficiency (dMMR) in endometrial adenocarcinoma, which is important for identifying Lynch syndrome and guiding treatments.
- Conducting a retrospective analysis of 304 endometrial cancer cases from 2013 to 2022, the two-antibody method identified dMMR in 26.6% of samples, showing a high agreement (98.8%) with the four-antibody panel, with only one case having differing results.
- The findings suggest that the two-antibody approach could serve as an effective
Mismatch repair deficiency: how reliable is the two-antibody approach? A national real-life study.
Histopathology
October 2024
Department of Pathology, Radboudumc, Nijmegen, The Netherlands.
Aims: Traditionally, mismatch repair (MMR) status is determined by a panel of four antibodies (MLH1, PMS2, MSH2, MSH6). If all proteins are retained, cases are MMR proficient (pMMR), while loss of one or more proteins is indicative of MMR deficiency (dMMR). This approach has been challenged in favour of a two-antibody approach, using PMS2 and MSH6 as a first screening.
View Article and Find Full Text PDFUnraveling the Properties of Phage Display Fab Libraries and Their Use in the Selection of Gliadin-Specific Probes by Applying High-Throughput Nanopore Sequencing.
Viruses
April 2024
Department of Nutrition and Food Sciences, School of Veterinary Sciences, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Directed evolution is a pivotal strategy for new antibody discovery, which allowed the generation of high-affinity Fabs against gliadin from two antibody libraries in our previous studies. One of the libraries was exclusively derived from celiac patients' mRNA (immune library) while the other was obtained through a protein engineering approach (semi-immune library). Recent advances in high-throughput DNA sequencing techniques are revolutionizing research across genomics, epigenomics, and transcriptomics.
View Article and Find Full Text PDFEvaluation of fendiline treatment in VP40 system with nucleation-elongation process: a computational model of Ebola virus matrix protein assembly.
Microbiol Spectr
April 2024
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
Unlabelled: Ebola virus (EBOV) infection is threatening human health, especially in Central and West Africa. Limited clinical trials and the requirement of biosafety level-4 laboratories hinder experimental work to advance our understanding of EBOV and the evaluation of treatment. In this work, we use a computational model to study the assembly and budding process of EBOV and evaluate the effect of fendiline on these processes in the context of fluctuating host membrane lipid levels.
View Article and Find Full Text PDFNavigating the Complex Landscape of Ebola Infection Treatment: A Review of Emerging Pharmacological Approaches.
Infect Dis Ther
January 2024
Faculdade de Farmácia, Universidade de Lisboa, 1649-003, Lisbon, Portugal.
In 1976 Ebola revealed itself to the world, marking the beginning of a series of localized outbreaks. However, it was the Ebola outbreak that began in 2013 that incited fear and anxiety around the globe. Since then, our comprehension of the virus has been steadily expanding.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!