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Medline ® Abstract for Reference 108

of 'Adjuvant chemotherapy for resected stage II colon cancer'

Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study.
Etienne-Grimaldi MC, Mahamat A, Chazal M, Laurent-Puig P, Olschwang S, Gaub MP, Formento JL, Formento P, Sudaka A, Boige V, Abderrahim-Ferkoune A, Benchimol D, AndréT, Houry S, Faucheron JL, Letoublon C, Gilly FN, Delpero JR, Lasser P, Pradere B, Pezet D, Penault-Llorca F, Milano G
Br J Cancer. 2014 May;110(11):2728-37. Epub 2014 May 06.
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.
Oncopharmacology and Pathology Departments, Centre Antoine-Lacassagne, Nice, France.