Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer
Tumor DNA mismatch repair (MMR) deficiency testing is important to the identification of Lynch syndrome and decision making regarding adjuvant chemotherapy in stage II colorectal cancer (CRC) and has become an indispensable test in metastatic tumors due to the high efficacy of immune checkpoint inhi...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/11/10/1567 |
| _version_ | 1797765978414645248 |
|---|---|
| author | Camille Evrard Gaëlle Tachon Violaine Randrian Lucie Karayan-Tapon David Tougeron |
| author_facet | Camille Evrard Gaëlle Tachon Violaine Randrian Lucie Karayan-Tapon David Tougeron |
| author_sort | Camille Evrard |
| collection | DOAJ |
| description | Tumor DNA mismatch repair (MMR) deficiency testing is important to the identification of Lynch syndrome and decision making regarding adjuvant chemotherapy in stage II colorectal cancer (CRC) and has become an indispensable test in metastatic tumors due to the high efficacy of immune checkpoint inhibitor (ICI) in deficient MMR (dMMR) tumors. CRCs greatly benefit from this testing as approximately 15% of them are dMMR but only 3% to 5% are at a metastatic stage. MMR status can be determined by two different methods, microsatellite instability (MSI) testing on tumor DNA, and immunohistochemistry of the MMR proteins on tumor tissue. Recent studies have reported a rate of 3% to 10% of discordance between these two tests. Moreover, some reports suggest possible intra- and inter-tumoral heterogeneity of MMR and MSI status. These issues are important to know and to clarify in order to define therapeutic strategy in CRC. This review aims to detail the standard techniques used for the determination of MMR and MSI status, along with their advantages and limits. We review the discordances that may arise between these two tests, tumor heterogeneity of MMR and MSI status, and possible explanations. We also discuss the strategies designed to distinguish sporadic versus germline dMMR/MSI CRC. Finally, we present new and accurate methods aimed at determining MMR/MSI status. |
| first_indexed | 2024-03-12T20:18:51Z |
| format | Article |
| id | doaj.art-c293c0b7ebb64aa7837684a27d9dfe82 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T20:18:51Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c293c0b7ebb64aa7837684a27d9dfe822023-08-02T01:10:20ZengMDPI AGCancers2072-66942019-10-011110156710.3390/cancers11101567cancers11101567Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal CancerCamille Evrard0Gaëlle Tachon1Violaine Randrian2Lucie Karayan-Tapon3David Tougeron4Department of Medical Oncology, Poitiers University Hospital, 86021 Poitiers, FranceDepartment of Cancer Biology, Poitiers University Hospital, 86021 Poitiers, FranceFaculty of Medicine, University of Poitiers, 86000 Poitiers, FranceDepartment of Cancer Biology, Poitiers University Hospital, 86021 Poitiers, FranceDepartment of Medical Oncology, Poitiers University Hospital, 86021 Poitiers, FranceTumor DNA mismatch repair (MMR) deficiency testing is important to the identification of Lynch syndrome and decision making regarding adjuvant chemotherapy in stage II colorectal cancer (CRC) and has become an indispensable test in metastatic tumors due to the high efficacy of immune checkpoint inhibitor (ICI) in deficient MMR (dMMR) tumors. CRCs greatly benefit from this testing as approximately 15% of them are dMMR but only 3% to 5% are at a metastatic stage. MMR status can be determined by two different methods, microsatellite instability (MSI) testing on tumor DNA, and immunohistochemistry of the MMR proteins on tumor tissue. Recent studies have reported a rate of 3% to 10% of discordance between these two tests. Moreover, some reports suggest possible intra- and inter-tumoral heterogeneity of MMR and MSI status. These issues are important to know and to clarify in order to define therapeutic strategy in CRC. This review aims to detail the standard techniques used for the determination of MMR and MSI status, along with their advantages and limits. We review the discordances that may arise between these two tests, tumor heterogeneity of MMR and MSI status, and possible explanations. We also discuss the strategies designed to distinguish sporadic versus germline dMMR/MSI CRC. Finally, we present new and accurate methods aimed at determining MMR/MSI status.https://www.mdpi.com/2072-6694/11/10/1567microsatellite instabilitycolorectal cancerimmune checkpointsdeficient mismatch repair |
| spellingShingle | Camille Evrard Gaëlle Tachon Violaine Randrian Lucie Karayan-Tapon David Tougeron Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer Cancers microsatellite instability colorectal cancer immune checkpoints deficient mismatch repair |
| title | Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer |
| title_full | Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer |
| title_fullStr | Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer |
| title_full_unstemmed | Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer |
| title_short | Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer |
| title_sort | microsatellite instability diagnosis heterogeneity discordance and clinical impact in colorectal cancer |
| topic | microsatellite instability colorectal cancer immune checkpoints deficient mismatch repair |
| url | https://www.mdpi.com/2072-6694/11/10/1567 |
| work_keys_str_mv | AT camilleevrard microsatelliteinstabilitydiagnosisheterogeneitydiscordanceandclinicalimpactincolorectalcancer AT gaelletachon microsatelliteinstabilitydiagnosisheterogeneitydiscordanceandclinicalimpactincolorectalcancer AT violainerandrian microsatelliteinstabilitydiagnosisheterogeneitydiscordanceandclinicalimpactincolorectalcancer AT luciekarayantapon microsatelliteinstabilitydiagnosisheterogeneitydiscordanceandclinicalimpactincolorectalcancer AT davidtougeron microsatelliteinstabilitydiagnosisheterogeneitydiscordanceandclinicalimpactincolorectalcancer |