Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-05

AUTHORS

M-C Etienne-Grimaldi, A Mahamat, M Chazal, P Laurent-Puig, S Olschwang, M-P Gaub, J-L Formento, P Formento, A Sudaka, V Boige, A Abderrahim-Ferkoune, D Benchimol, T André, S Houry, J-L Faucheron, C Letoublon, F-N Gilly, J-R Delpero, P Lasser, B Pradere, D Pezet, F Penault-Llorca, G Milano

ABSTRACT

BACKGROUND: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. METHODS: This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH. RESULTS: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR. CONCLUSIONS: Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy. More... »

PAGES

2728

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2014.213

DOI

http://dx.doi.org/10.1038/bjc.2014.213

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006693149

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24800948


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