The DOI matches its Crossref record; 102 of the 102 references it cites were found in a registry or an index.
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
Open accessAbstract
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.
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Metadata
- Authors
- Luchini, C., Bibeau, F., Ligtenberg, M. J. L., Singh, N., Nottegar, A., Bosse, T., Miller, R., Riaz, N., Douillard, J.-Y., Andre, F., & Scarpa, A.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 30
- Issue
- 8
- Pages
- 1232-1243
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2944675676
- Cited by
- 1,041
- References
- 102
- FWCI
- 12.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Luchini, C., Bibeau, F., Ligtenberg, M. J. L., Singh, N., Nottegar, A., Bosse, T., Miller, R., Riaz, N., Douillard, J.-Y., Andre, F., & Scarpa, A. (2019). 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. Annals of Oncology. https://doi.org/10.1093/annonc/mdz116
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