Immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in gastroesophageal reflux disease.
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.
Nishiyama
Yorihiro
Y
Department of Gastroenterology, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
Koyama
Shigeki
S
Andoh
Akira
A
Moritani
Suzuko
S
Kushima
Ryoji
R
Fujiyama
Yoshihide
Y
Hattori
Takanori
T
Bamba
Tadao
T
D001485:Basement Membrane / Q000473:pathology; D001706:Biopsy / Q000379:methods*; D018797:Cell Cycle Proteins / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000032:analysis*; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000473:pathology*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D009092:Mucous Membrane / Q000473:pathology; D012720:Severity of Illness Index; D013525:Surgical Instruments; D025521:Tumor Suppressor Proteins / Q000032:analysis*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27