Integrating TYMS, KRAS and BRAF testing in patients with metastatic colorectal cancer.

摘要: AIM To investigate the impact of thymidylate synthase (TYMS), KRAS and BRAF in survival metastatic colorectal cancer (mCRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectively from records consecutive mCRC fluoropyrimidine-based chemotherapy 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues retrieved for analysis. TYMS genotypes identified restriction fragment analysis PCR, while mutation status was evaluated using real-time PCR assays. gene polymorphisms each 3' untranslated region (UTR) 5'UTR classified into three groups according probability they have high, medium low expression (and similar levels risk) based on evidence previous studies. Univariate multivariate analyses performed. RESULTS The recovered 89 (46.1% de novo disease 53.9% relapsed). Of these, 46 (51.7%) had colon 43 (48.3%) rectal as primary. All (5FU or capecitabine) single-agent combination irinotecan or/and oxaliplatin bevacizumab. With a median follow-up time 14.8 mo (range 0-119.8), 85 (95.5%) experienced progression, 63 deaths (70.8%) recorded. 3-year 5-year OS rate 25.4% 7.7% progression-free 7.1%. Multivariate polymorphisms, clinicopathological parameters indicated that 3'UTR are associated risk progression death (P < 0.05 P 0.03 respectively). When compared tumors without any del allele (genotypes ins/ins ins/loss heterozygosity (LOH) linked high expression) del/del genotype (low group) ins/del del/LOH (intermediate lower (HR = 0.432, 95%CI: 0.198-0.946, 0.04 HR 0.513, 0.287-0.919, respectively) 0.366, 0.162-0.827, 0.02 0.559, 0.309-1.113, 0.06 Additionally, independently 1.600, 1.011-2.531, 0.05). addition 1st line 0.600, 0.372-0.969, 0.352, 0.164-0.757, 0.01 CONCLUSION ins/LOH associate worst prognosis under Large prospective studies needed validation our findings.