TFAP2E Methylation and Expression Status Does Not Predict Response to 5-FU-based Chemotherapy in Colorectal Cancer

Purpose: A recent study reported that 5 -fluorouracil (5-FU)based dientotherapy is less effective in treating patients with advanced colorectal cancer demonstrating hypermethylation of the TFAP2E gene. The aim of our study was to confirm and validate these findings in large, uniformly treated, wellcharacterized patient cohorts. Experimental Design: Two cohorts of 783 patients with colorectal cancer: 532 from a population-based, multicenter cohort (FPICOLON I) and 251 patients from a clinic-based trial were used to study the effectiveness of TFAP2E methylation and expression as a predictor of response of colorectal cancer patients to 5-FU-based chemotherapy. DNA methylation status of the TFAP2E gene in patients with colorectal cancer was assessed by quantitative hisulfite pyrosequencing analysis. IHC analysis of the TFAP2E protein expression was also performed. Results: Correlation between TFAP2E methylation status and IHC staining was performed in 607 colorectal cancer samples. Among 357 hypermethylated tumors, only 141 (39.6%) exhibited loss of protein expression. Survival was not affected by TFAP2E hypermethylation in stage IV patients PIK 1.21; 95% confidence interval (CI), 0.79-1.87; log-rank P = 0.6]. In stage II-III cases, disease-free survival was not influenced by TEAP2E hypermethylation status in 5-FU-treated (HR, 0.91; 95% Cl, 0.51 1.59; log-rank P = 0.9) as well as in nontreated patients (HR, 88; 95% CI, 0 5 - 1 .54; log-rank P = 0.7). Conclusions: TFAP2E hypemiethylation does nut correlate with loss of its protein expression. Our large, systematic, and comprehensive study indicates that TEAP2E methylation and expression may not play a major role in predicting response to 5-FU-based chemotherapy in patients with colorectal cancer. (C) 2018 AACR.