title: Role of immunohistochemical markers in predicting progression of dysplasia to advanced neoplasia in patients with ulcerative colitis.
abstract: BACKGROUND
  Although dysplasia is thought to be the precursor lesion in the development of colitis-associated colorectal cancer (CRC), a significant proportion of patients with ulcerative colitis (UC) and low-grade (LGD) or indefinite (IND) dysplasia remain cancer-free during endoscopic follow-up. There is a need for biomarkers that predict neoplastic progression. We studied the value of a series of immunohistochemical markers in UC patients with flat LGD or IND with regard to neoplastic progression.
  
  
  METHODS
  Tissue samples were collected from 12 UC patients (six flat LGD, six IND) without progression and from 10 UC patients (eight flat LGD, two IND) with documented progression to HGD and/or CRC during a median of 25 and 23 months of colonoscopic follow-up, respectively. Immunohistochemistry using monoclonal antibodies was performed for p53, CD44, Ki67, AMACR, β-catenin, cyclin D1, p21, and ALDH. Positive and negative staining patterns were compared for progression to advanced neoplasia.
  
  
  RESULTS
  When patients showed coexpression of p53 and AMACR, 6/7 patients (86%) developed advanced neoplasia, compared to 4/15 patients (27%) without p53/AMACR coexpression (P = 0.02). Patients with p53/AMACR coexpression developed advanced neoplasia in a time period of 19 months (median, range 1-101) compared to 80 months (median, range 8-169) in patients without p53/AMACR coexpression (P = 0.14). Interestingly, in three patients with progression and previous dysplasia-negative biopsies, two out of three biopsies were p53-positive a median of 12 months (range 10-14) before the LGD/IND diagnosis.
  
  
  CONCLUSIONS
  This study suggests a role for p53/AMACR coexpression as a potential marker of neoplastic progression in patients with UC.
authors.affiliation: University Medical Center Utrecht, Department of Gastroenterology and Hepatology, Utrecht, The Netherlands.
authors.forename: Fiona D M
authors.initials: FD
authors.lastname: van Schaik
authors.forename: Bas
authors.initials: B
authors.lastname: Oldenburg
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Marguerite E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: Frank P
authors.initials: FP
authors.lastname: Vleggaar
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Martijn G H
authors.initials: MG
authors.lastname: van Oijen
authors.forename: Fiebo J W
authors.initials: FJ
authors.lastname: Ten Kate
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D019998:Racemases and Epimerases / Q000378:metabolism; D018709:Statistics, Nonparametric; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; C493956:CDKN1A protein, human; C495270:CTNNB1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D019938:Cyclin D1; D000444:Aldehyde Dehydrogenase; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase