| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach |
| Creator | Luchini et al. |
| Author | C. Luchini |
| Author | F. Bibeau |
| Author | M. J. L. Ligtenberg |
| Author | N. Singh |
| Author | A. Nottegar |
| Author | T. Bosse |
| Author | R. Miller |
| Author | N. Riaz |
| Author | J.-Y. Douillard |
| Author | F. Andre |
| Author | A. Scarpa |
| Abstract | BACKGROUND: Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy. METHODS: To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression. RESULTS: The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: 'microsatellites', 'MSI', 'DNA mismatch repair' and 'features of MSI tumour'. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types. CONCLUSIONS: This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1. |
| Publication | Annals of Oncology: Official Journal of the European Society for Medical Oncology |
| Date | May 06, 2019 |
| Journal Abbr | Ann. Oncol. |
| Language | eng |
| DOI | 10.1093/annonc/mdz116 |
| ISSN | 1569-8041 |
| Short Title | ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden |
| Library Catalog | PubMed |
| Extra | PMID: 31056702 |
| Tags | Antineoplastic Agents, Immunological, B7-H1 Antigen, Biomarkers, Tumor, clinic, DNA Mutational Analysis, European Union, Genetic Testing, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, Medical Oncology, Microsatellite Instability, microsatellite instability (MSI), Mutation, Neoplasms, next-generation sequencing (NGS), Patient Selection, Practice Guidelines as Topic, Programmed Cell Death 1 Receptor, Societies, Medical, tumour mutational burden (TMB), tumour mutational load (TML) |
| Date Added | 2019/05/14 - 08:06:10 |
| Date Modified | 2020/07/24 - 16:15:15 |
| Notes and Attachments | PubMed entry (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
