Immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in gastroesophageal reflux disease

J Gastroenterol. 2002;37(11):905-11. doi: 10.1007/s005350200152.

Abstract

Background: The aim of this study was to carry out an immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in endoscopic biopsy samples obtained using angled biopsy forceps.

Methods: The study was based on the examination of endoscopic esophageal biopsy specimens obtained from 46 patients with evidence of reflux and from 10 normal control subjects without clinical reflux.

Results: The percentage of samples containing the lamina propria was 5.7% using standard forceps ( n = 53) and 83.3% using the angled forceps ( n= 67). The use of angled forceps allowed the detection of inflammatory cell accumulation in the lamina propria even in patients with modified Los Angeles (LA) system grades N and M. In normal esophageal mucosa, Ki-67-positive cells were detected within the lower parts of the basal zone, and p21- and p27-positive cells were not detected. In samples from grade N and M patients, no histological changes were detectable by standard H&E staining. However, the area of Ki-67-positive cells was slightly expanded compared with normal mucosa, and p21- and p27-positive cells were clearly detectable from the lower to middle part of the epithelium. The area of Ki-67-, p21-, and p27-positive cells tended to expand upward in the epithelium with gastroesophageal reflux disease (GERD) severity based on the LA classification grading.

Conclusions: The use of angled biopsy forceps allows the evaluation of inflammatory responses at the level of the lamina propria and makes it possible to assess the expression of cell cycle-regulating proteins in the entire epithelium. The evaluation of these responses may be helpful in the diagnosis of endoscopically negative GERD.

MeSH terms

  • Basement Membrane / pathology
  • Biopsy / methods*
  • Cell Cycle Proteins / analysis*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / analysis*
  • Enzyme Inhibitors / analysis*
  • Esophagoscopy
  • Esophagus / pathology
  • Gastroesophageal Reflux / pathology*
  • Humans
  • Ki-67 Antigen / analysis*
  • Mucous Membrane / pathology
  • Severity of Illness Index
  • Surgical Instruments
  • Tumor Suppressor Proteins / analysis*

Substances

  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Ki-67 Antigen
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27