title: Prognostic role of carcinoembryonic antigen is influenced by microsatellite instability genotype and stage in locally advanced colorectal cancers.
abstract: BACKGROUND
  Carcinoembryonic antigen (CEA) is the most frequently used marker for colorectal cancer (CRC). Influence of genetic instability on tumor marker expression is not known. The aim of this study was to investigate microsatellite instability (MSI) of CEA serum levels in locally advanced CRC.
  
  
  METHODS
  The observational cohort consisted of stage II-III CRC patients (n = 131) 75 years old or youngerwho underwent surgery with curative intent. CEA serum levels were measured before (preCEA) and immediately after surgery (postCEA). DNA from the extracted tumors was investigated for MSI. Survival was analyzed in univariate and multivariate analyses.
  
  
  RESULTS
  The median preCEA was 3 U/ml (IQR = 1-3, range = 1-136 U/ml). Stage III cancers with MSI had an elevated preCEA more often than those without MSI (25% vs. 0%; p = 0.026). A preCEA >10 U/ml was significantly associated with elevated postCEA (CEA >1 U/ml; odds ratio [OR] = 5.4, 95% CI = 2.1-14.2; p < 0.001). Survival wasnot significantly different between those with postCEA <10 U/ml vs. postCEA ≥ 10 U/ml or when stratified by MSI status. A cutoff of postCEA ≤ 1 U/ml conferred significantly improved survival compared to higher CEA levels. Stratified for MSI status, this difference was significant for microsatellite stable (MSS) cancers only (p = 0.021). In multivariate analysis, postCEA >1 U/ml (hazard ratio [HR] = 3.5, 95% CI = 1.7-7.3, p = 0.001) and stage III (HR = 6.7, 95% CI = 3.0-14.9; p < 0.001) were predictors of decreased survival.
  
  
  CONCLUSIONS
  Preoperative CEA levels were significantly higher in stage III cancers with the MSI genotype, and high preoperative CEA was associated with increased postoperative CEA. Absent postoperative CEA in serum conferred improved long-term survival.
authors.affiliation: Department of Surgery, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway. ksoreide@mac.com
authors.forename: Kjetil
authors.initials: K
authors.lastname: Søreide
authors.forename: Jon Arne
authors.initials: JA
authors.lastname: Søreide
authors.forename: Hartwig
authors.initials: H
authors.lastname: Kørner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002272:Carcinoembryonic Antigen / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D003082:Colectomy / Q000379:methods / Q000401:mortality; D015179:Colorectal Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011182:Postoperative Care; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen