p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
; : 208-215, 2016.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-170064
Responsible library:
WPRO
ABSTRACT
PURPOSE:
Hypermethylation of the CpG island of p16(INK4a) occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab. MATERIALS ANDMETHODS:
Pyrosequencing was used to identify KRAS mutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome.RESULTS:
Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRAS mutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation hazard ratio [HR], 3.21; p=0.017; p16 methylation HR, 2.97; p=0.027).CONCLUSION:
Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Phenotype
/
DNA
/
Colorectal Neoplasms
/
Logistic Models
/
Leucovorin
/
Multivariate Analysis
/
CpG Islands
/
Genes, p16
/
Cyclin-Dependent Kinase Inhibitor p16
/
Drug Therapy
Type of study:
Prognostic study
/
Risk factors
Limits:
Humans
Language:
English
Journal:
Cancer Research and Treatment
Year:
2016
Document type:
Article