title: IGFBP-3 Gene Methylation in Primary Tumor Predicts Recurrence of Stage II Colorectal Cancers.
abstract: OBJECTIVE
  To evaluate the influence of IGFBP-3 methylation on recurrence in patients with stage II colorectal cancer (CRC) from 2 independent cohorts.
  
  
  BACKGROUND
  The relationship between IGFBP-3 methylation in primary tumors (PTs) or lymph nodes (LNs) and risk of recurrence in patients with stage II CRC treated with surgery alone is unknown.
  
  
  METHODS
  IGFBP-3 methylation of DNA from 115 PTs and 1641 LNs in patients with stage II CRC from 2 independent cohorts was analyzed. Forty patients developed recurrence, whereas 75 matched patients remained recurrence free for more than 2 years after surgery. Cox proportional hazard models were used to calculate hazard ratios (HRs) of recurrence, adjusted for patient and tumor characteristics.
  
  
  RESULTS
  Methylation of IGFBP-3 in PTs was identified to be significantly associated with risk of recurrence in the training set. The signature was tested in a validation set and classified 40.7% of patients as high risk. Five-year recurrence-free survival rates were 76.4% and 58.3% for low- and high-risk patients, respectively, with an HR of 2.21 (95% confidence interval, 1.04-4.68; P = 0.039). In multivariate analysis, the signature remained the most significant prognostic factor, with an HR of 2.40 (95% confidence interval, 1.10-5.25; P = 0.029). A combined analysis of 1641 LNs from the 2 sets identified IGFBP-3 methylation in LNs was not associated with risk of recurrence.
  
  
  CONCLUSIONS
  Detection of IGFBP-3 methylation in PTs, but not in LNs, provides a powerful tool for the identification of patients with stage II CRC at high risk of recurrence.
authors.affiliation: *Department of Gastrointestinal Surgery, Daping Hospital, Third Military Medical University, Chongqing, China †Department of Surgery ‡Department of Oncology, The Sydney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD §Department of Pathology and David Rubenstein Pancreatic Cancer Research Center, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Tao
authors.initials: T
authors.lastname: Fu
authors.forename: Emmanouil P
authors.initials: EP
authors.lastname: Pappou
authors.forename: Angela A
authors.initials: AA
authors.lastname: Guzzetta
authors.forename: Marilia de Freitas
authors.initials: Mde F
authors.lastname: Calmon
authors.forename: Lifeng
authors.initials: L
authors.lastname: Sun
authors.forename: Alexander
authors.initials: A
authors.lastname: Herrera
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Baylin
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Weidong
authors.initials: W
authors.lastname: Tong
authors.forename: Nita
authors.initials: N
authors.lastname: Ahuja
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3
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