Beschreibung:
<jats:p> 515 </jats:p><jats:p> Background: Transcription factor AP-2ε, a member of the AP-2 family has been extensively studied in many cancers. Recently, it has been suggested that the gene encoding AP-2ε (TFAP2E) is involved in the development of colorectal cancer (CRC) and is also associated with clinical non-responsiveness to chemotherapy in CRCs. Therefore, we have investigated the clinical significance of TFAP2E methylation status in patients with metastatic CRCs who have received combination chemotherapy with fluoropyrimidine, leucovorin, and irinotecan (FOLFIRI) as first-line treatment. Methods: Eligible patients were those with metastatic CRC treated at Asan Medical center from Jan 2009 to June 2012, and treated with first-line FOLFIRI chemotherapy. The patients without available surgical tissue were excluded. A total of 94 patients were finally included in the study. Results: Forty patients (43%) showed TFAP2E hypermethylation (HM group), and 54 patients (57%) showed TFAP2E hypomethylation (LM group). There were no statistically significant differences in the baseline characteristics according to TFAF2E methylation status. Response rate to chemotherapy was not significantly different between 2 groups (response rate, 50% in HM vs. 36% in LM group, p=0.200; disease control rate, 87% in HM vs. 85% in LM group, p=0.819). After a median follow-up duration of 39.9 months, both progression-free survival (PFS) and overall survival (OS) were not significantly different between 2 groups (HM group vs. LM group; PFS, 5.93 months vs. 5.90 months, p=0.893; OS, 20.9 months vs. 19.8 months, p=0.966). Multivariate analysis showed that there was no significant factor associated with PFS. The patients with well or moderately differentiated tumors showed better OS compared to those with poorly differentiated or mucinous tumors (hazard ratio 0.27, 95% confidence interval 0.13-0.55, p<0.001). However, TFAP2E methylation status was not an independent factor affecting neither PFS nor OS. Conclusions: TFAP2E methylation status may not be a useful biomarker in predicting the clinical outcomes in patients with metastatic colorectal cancers who have received first-line FOLFIRI chemotherapy. </jats:p>