title: The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy.
abstract: BACKGROUND
  Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear.
  
  
  METHODS
  A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status.
  
  
  RESULTS
  CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022).
  
  
  CONCLUSIONS
  Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Min
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Bae
authors.forename: Eui Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Hong Suk
authors.initials: HS
authors.lastname: Yu
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Chang
authors.forename: Hee Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Cheol Keun
authors.initials: CK
authors.lastname: Park
authors.forename: Suk-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D003131:Combined Modality Therapy; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D045643:DNA Repair Enzymes; D005472:Fluorouracil