Keratin 7 expression as an early marker of reflux-related columnar mucosa without intestinal metaplasia in the esophagus
Daniela Cabibi, Eugenio Fiorentino, Gianni Pantuso, Achille Mastrosimone, Cosimo Callari, Matilde Cacciatore, Maria Campione, Francesco Aragona
Med Sci Monit 2009; 15(5): CR203-210
Available online: 2009-04-23
The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated.
Material and Method: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed.
Results: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%).
Conclusions: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux.
Keywords: Intestines - pathology, Keratin-7 - metabolism, Helicobacter pylori - isolation & purification, Case-Control Studies, Esophagogastric Junction - pathology, Biological Markers - metabolism, Barrett Esophagus - pathology, Metaplasia