title: Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients.
abstract: OBJECTIVE
  To investigate the clinicopathologic characteristics and prognostic implications associated with loss of CDX2 expression in colorectal cancers (CRCs).
  
  
  METHODS
  We immunohistochemically evaluated CDX2 expression in 713 CRCs and paired our findings to clinicopathologic and molecular characteristics of each individual. Endpoints included cytokeratin 7 and CK20 expression, microsatellite instability, CpG island methylator phenotype, and KRAS and BRAF mutation statuses. Univariate and multivariate survival analysis was performed to reveal the prognostic value of CDX2 downregulation.
  
  
  RESULTS
  CDX2 expression was lost in 42 (5.9%) patients. Moreover, loss of CDX2 expression was associated with proximal location, infiltrative growth, advanced T, N, M and overall stage. On microscopic examination, loss of CDX2 expression was associated with poor differentiation, increased number of tumor-infiltrating lymphocytes, luminal serration and mucin production. Loss of CDX2 expression was also associated with increased CK7 expression, decreased CK20 expression, CpG island methylator phenotype, microsatellite instability and BRAF mutation. In a univariate survival analysis, patients with loss of CDX2 expression showed worse overall survival (P < 0.001) and progression-free survival (P < 0.001). In a multivariate survival analysis, loss of CDX2 expression was an independent poor prognostic factor of overall survival [hazard ratio (HR) = 1.72, 95%CI: 1.04-2.85, P = 0.034] and progression-free survival (HR = 1.94, 95%CI: 1.22-3.07, P = 0.005).
  
  
  CONCLUSIONS
  Loss of CDX2 expression is associated with aggressive clinical behavior and can be used as a prognostic marker in CRCs.
authors: Jeong Mo Bae, Tae Hun Lee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors: Jeong Mo
authors: JM
authors: Bae
authors: Jeong Mo Bae, Tae Hun Lee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors: Tae Hun
authors: TH
authors: Lee
authors: Jeong Mo Bae, Tae Hun Lee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors: Nam-Yun
authors: NY
authors: Cho
authors: Jeong Mo Bae, Tae Hun Lee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors: Tae-You
authors: TY
authors: Kim
authors: Jeong Mo Bae, Tae Hun Lee, Nam-Yun Cho, Gyeong Hoon Kang, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors: Gyeong Hoon
authors: GH
authors: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D000071616:CDX2 Transcription Factor; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins
keywords: CDX2; Colorectal cancer; CpG island methylator phenotype; Microsatellite instability; Survival