Mismatch repair deficiency: how reliable is the two-antibody approach? A national real-life study.
Publication year
2024Source
Histopathology, 85, 4, (2024), pp. 639-648ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Pathology
Journal title
Histopathology
Volume
vol. 85
Issue
iss. 4
Page start
p. 639
Page end
p. 648
Subject
Pathology - Radboud University Medical CenterAbstract
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.
This item appears in the following Collection(s)
- Academic publications [245054]
- Electronic publications [132354]
- Faculty of Medical Sciences [93209]
- Open Access publications [105958]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.