Immunohistochemical expression of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in inflammatory bowel disease: correlation with other cell-cycle-related proteins (Rb, p53, ki-67 and PCNA) and clinicopathological features

Int J Colorectal Dis. 2004 Jul;19(4):325-33. doi: 10.1007/s00384-003-0571-3. Epub 2004 Apr 2.

Abstract

Background and aims: The expression patterns of cyclins D1 and E as well as cyclin-dependent kinase inhibitors p21/waf1 and p27/kip1 and their correlation with clinical parameters and other cell cycle regulators was investigated in inflammatory bowel disease (IBD).

Patients and methods: These molecular markers were localized immunohistochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10) and anti-p27 (1B4) in 70 patients with IBD, 30 patients with colorectal cancer and eight healthy subjects. Data were analyzed statistically using the software program.

Results: Cyclin D1 expression was higher in both UC and CD compared with the healthy control group. In addition, CD cyclin D1 expression was higher compared with UC cases and colorectal carcinomas. Cyclin D1 expression was correlated with disease activity and cell proliferation in UC cases. A positive relationship of cyclin D1 with p27/kip1 in both UC and CD was detected. Cyclin E expression was higher in UC, CD and carcinomas compared with healthy control group and its expression correlated with proliferative activity in both UC and CD cases. p21/waf1 expression was higher in IBD cases compared with that of the control group, while a decreased p21/waf1 expression in the group of carcinomas was noted. This expression was correlated with disease activity in UC and the proliferative activity in both UC and CD. The expression of cyclins D1 and E as well as p21/waf1 was also correlated with the existence of dysplastic lesions. A lower p27/kip1 expression in the group of carcinomas compared with IBD cases and healthy controls was found.

Conclusions: The expression patterns of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in IBD may indicate their contribution in epithelial cell turnover and their possible implication in IBD-related dysplasia-carcinoma.

MeSH terms

  • Carcinoma / metabolism
  • Carrier Proteins / metabolism*
  • Case-Control Studies
  • Cell Division
  • Colorectal Neoplasms / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Precancerous Conditions / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Retinoblastoma Protein / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDKN1A protein, human
  • CDKN1B protein, human
  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Intracellular Signaling Peptides and Proteins
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases