| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency |
| Creator | Cohen et al. |
| Author | R. Cohen |
| Author | O. Buhard |
| Author | P. Cervera |
| Author | E. Hain |
| Author | A. Bardier |
| Author | J.-B. Bachet |
| Author | J.-M. Gornet |
| Author | D. Lopez-Trabada |
| Author | S. Dumont |
| Author | R. Kaci |
| Author | P. Bertheau |
| Author | F. Renaud |
| Author | F. Bibeau |
| Author | Y. Parc |
| Author | D. Vernerey |
| Author | A. Duval |
| Author | M. Svrcek |
| Author | Thierry André |
| Abstract | BACKGROUND: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs. PATIENTS AND METHODS: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation. RESULTS: Among 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (37%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44). CONCLUSIONS: LS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations. |
| Publication | European Journal of Cancer (Oxford, England: 1990) |
| Volume | 86 |
| Pages | 266-274 |
| Date | 11 2017 |
| Journal Abbr | Eur. J. Cancer |
| Language | eng |
| DOI | 10.1016/j.ejca.2017.09.022 |
| ISSN | 1879-0852 |
| Library Catalog | PubMed |
| Extra | PMID: 29055842 |
| Tags | Adult, Aged, Biomarkers, Tumor, BRAF mutation, Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis, Diagnosis, Differential, Disease-Free Survival, DNA Methylation, Female, France, Genetic Predisposition to Disease, Heredity, Humans, Immunotherapy, Kaplan-Meier Estimate, Lynch syndrome, Male, Microsatellite Instability, Middle Aged, Mismatch repair, Molecular Diagnostic Techniques, Multivariate Analysis, Mutation, MutL Protein Homolog 1, Neoplasm Metastasis, original, Pedigree, Phenotype, Predictive Value of Tests, Proportional Hazards Models, Proto-Oncogene Proteins B-raf, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome |
| Date Added | 2018/11/13 - 17:24:57 |
| Date Modified | 2019/05/21 - 13:41:51 |
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