667 Background: The prognostic role of CpG Island Methylator Phenotype (CIMP) in colorectal cancer (CRC) is still controversial, especially in metastatic CRC. Methods: We retrospectively analyzed the CpG island methylator phenotype (CIMP) in stage I to IV CRC specimens, which were diagnosed during 2005-2013. CIMP status was determined using a 5- gene MethyLight-based assay ( p16, MINT1, MINT2, MINT31, and MLH1). Tumors were designated as CIMP if 3 or more of 5 genes gave percent of methylated reference value ≧ 10. The clinicopatholoical characteristics, anti-cancer therapies, and the overall survival outcome were reviewed. Overall survival (OS) was compared between patients with CIMP CRC and those with non-CIMP CRC. Results: Among 450 patients with successfully determined CIMP status, 259 (57.56%) were male, 312 (70.31%) were stages I-III, 316 (70.69%) were left-sided CRC. In the survival analyses in stages I-IV patients, there was no significant difference in OS between those with or without CIMP (long rank test, p = 0.4526). Importantly, patients with metastatic CIMP CRC had poor OS than those with metastatic non-CIMP CRC (median survival, CIMP vs. non-CIMP: 1.36 vs. 3.11 years, log rank test, p = 0.0047). In a multivariate analysis, which adjusted prognostic variables such as: KRAS and BRAF mutations, microsatellite instability status, age, sex, grade, primary site, metastatic site number, chemotherapies and targeted therapies, CIMP remained an independent poor prognostic factor for OS (HR = 6.213, 95% confidence interval: 2.443 to 15.799, p = 0.0001) in metastatic CRC. In an exploratory analysis, there were more tumors with liver metastases at diagnosis in CIMP CRC than in non-CIMP CRC (94.4% vs. 71.3%, p = 0.0416). Conclusions: Our data demonstrated CIMP might independently predict poor survival in metastatic CRC in a large East Asian cohort.
The Role of the CpG Island Methylator Phenotype in Colorectal Cancer Prognosis Depends on Microsatellite Instability Screening Status