title: Biomarker-based prediction of inflammatory bowel disease-related colorectal cancer: a case-control study.
abstract: BACKGROUND
  Regular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy.
  
  
  METHODS
  A case-control study was performed to determine the prognostic value of DNA ploidy and p53 in IBD-related neoplasia. Cases with IBD-related colorectal cancer (CRC), detected in our surveillance program between 1985-2008, were selected and matched with two controls, for age, gender, disease characteristics, interval of follow-up, PSC, and previous surgery. Biopsies were assessed for DNA ploidy, p53, grade of inflammation and neoplasia. Progression to neoplasia was analyzed with Cox regression analysis, adjusting for potentially confounding variables.
  
  
  RESULTS
  Adjusting for age, we found statistically significant Hazard ratios (HR) between development of CRC, and low grade dysplasia (HR5.5; 95%CI 2.6-11.5), abnormal DNA ploidy (DNA index (DI) 1.06-1.34, HR4.7; 95%CI 2.9-7.8 and DI>1.34, HR6.6; 95%CI 3.7-11.7) and p53 immunopositivity (HR3.0; 95%CI 1.9-4.7) over time. When adjusting for all confounders, abnormal DNA ploidy (DI 1.06-1.34, HR4.7; 95%CI 2.7-7.9 and DI>1.34, HR5.0; 95%CI 2.5-10.0) and p53 immunopositivity (HR1.7; 95%CI 1.0-3.1) remained statistically significant predictive of neoplasia.
  
  
  CONCLUSIONS
  In longstanding IBD, abnormal DNA ploidy and p53 immunopositivity are important risk factors of developing CRC. The yield of surveillance may potentially increase by adding these biomarkers to the routine assessment of biopsies.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands. monique.gerrits@mumc.nl
authors.forename: Monique M
authors.initials: MM
authors.lastname: Gerrits
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Myrte
authors.initials: M
authors.lastname: Theeuwes
authors.forename: Herman
authors.initials: H
authors.lastname: van Dekken
authors.forename: Marjolein
authors.initials: M
authors.lastname: Sikkema
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: C Janneke
authors.initials: CJ
authors.lastname: van der Woude
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D003082:Colectomy; D003106:Colon / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000150:complications*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53