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Updated: Sep 20, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Absence of microsatellite instability in extramammary Paget's disease
K Kashiwada-Nakamura1, T M Myangat1, I Kajihara1
1Department of Dermatology and Plastic Surgery Faculty of Life Sciences Kumamoto University Kumamoto Japan.
Background:
Deficiency of DNA mismatch repair (MMR) induces microsatellite instability (MSI). Pembrolizumab, an antibody targeting PD-1 (an immune checkpoint inhibitor), is more effective against MMR-deficient tumours than against MMR-proficient tumours. The status of MMR is a useful biomarker for predicting the effectiveness of pembrolizumab administration. Although the status of MMR has attracted attention in skin tumours, there are few reports on MSI in extramammary Paget's disease (EMPD).
Objectives:
To evaluate the status of MMR in patients with EMPD.
Materials & Methods:
One hundred one patients with EMPD were included. MMR status of the genomic DNA of each subject was analysed using Promega panel (approved as a companion diagnostic agent for the administration of pembrolizumab).
Results:
MSI testing showed the occurrence rates of MSI-high (more than two markers are unstable), MSI-low (one marker is unstable) and MSS (all markers are stable) tumour tissues were 0% (0/101), 1.0% (1/101) and 99.0% (100/101), respectively.
Conclusion:
The status of MMR may not be useful for the potential therapeutic application of pembrolizumab.
Insights
Microsatellite instability (MSI) testing in extramammary Paget's disease (EMPD) revealed very low rates of MSI-high or MSI-low tumors. Therefore, DNA mismatch repair (MMR) status may not be a reliable biomarker for predicting pembrolizumab effectiveness in EMPD patients.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- DNA mismatch repair (MMR) deficiency leads to microsatellite instability (MSI).
- MMR deficiency is a biomarker for predicting pembrolizumab effectiveness in certain cancers.
- Limited data exists on MSI in extramammary Paget's disease (EMPD).
Purpose of the Study:
- To evaluate the DNA mismatch repair (MMR) status in patients with extramammary Paget's disease (EMPD).
Main Methods:
- Analyzed MMR status in genomic DNA from 101 EMPD patients using the Promega panel.
- The Promega panel is an approved companion diagnostic for pembrolizumab.
Main Results:
- 99.0% of EMPD tumors were microsatellite stable (MSS).
- 1.0% of EMPD tumors showed low microsatellite instability (MSI-low).
- 0% of EMPD tumors were high microsatellite instability (MSI-high).
Conclusions:
- MMR status is unlikely to be a useful biomarker for predicting pembrolizumab efficacy in EMPD.
- Further research may be needed to identify predictive biomarkers for immunotherapy in EMPD.
