Immunohistochemical overexpression of the p53 protein and Ki-67 (MIB-1) antigen in patients with GERD and chronic esophagitis.

Patients with gastroesophageal reflux disease and Barrett esophagus have an increased risk of developing adenocarcinoma of the esophagus. It is uncertain whether molecular or proliferative alterations are present in the early stages of disease. One hundred thirty-eight patients with gastroesophageal reflux disease symptoms were subjected to upper gastrointestinal endoscopy with biopsies of the esophageal mucosa. p53 protein expression and the Ki-67 proliferation index were determined by immunohistochemical studies. Patients were divided into 4 groups according to histopathologic diagnosis: G1, normal epithelium (n=58); G2, mild esophagitis (n=42); G3, moderate esophagitis (n=23), and G4, severe esophagitis (n=15). p53 overexpression was detected in 7% of G1, 21.4% of G2, 52.2% of G3, and 60% of G4 patients. There were significant differences between G1 and G3 or G4 (P<0.001) and between G2 and G4 (P<0.05). The Ki-67 index was 21.3+/-19.5% in G1, 30.8+/-23.4% in G2, 47.1+/-23.2% in G3, and 48.3+/-25.7% in G4. Significant differences in the Ki-67 index were found between groups: G1 x G3 (P<0.001), G1 x G4 (P<0.001), G2 x G3 (P=0.026), and G2 x G4 (P=0.046). p53 and Ki-67 overexpression were correlated with the severity of esophagitis (P<0.001). p53 overexpression and the Ki-67 (MIB-1) index were correlated with histologic findings of inflammation in the esophageal mucosa, particularly in the moderate and severe forms of chronic esophagitis.