Cell proliferation of squamous epithelium in gastro-oesophageal reflux disease: correlations with clinical, endoscopic and morphological data

Background: The microscopic assessment of squamous epithelium lesions in gastro-oesophageal reflux disease (GERD) is subjective. The Ki67 nuclear antigen expressed by proliferating cells provides an objective measure of regeneration in the squamous epithelium. Aim: To evaluate Ki67 expression in GERD patients and controls, in comparison with histological lesions, pH-metry and endoscopic data. Methods: Eighty-seven patients with GERD symptoms and 20 symptom-free controls underwent endoscopy and 24-h pH monitoring. Oesophageal biopsies (4 cm, 2 cm and Z-line) were stained with Ki67/MIB-1 antibodies; the Ki67-positive nuclear area was assessed with an image analysis system and expressed as percentage of the whole epithelial area (Ki67-%). Results: Ki67-% was significantly higher in 32 patients with erosive oesophagitis, 44 endoscopy-negative GERD and 11 patients with functional heartburn than in controls (P = 0.0001). Both controls and patients showed a progressive increase in Ki67-% from 4 cm to the Z-line (P < 0.0001). Ki67-% showed a significant correlation with other conventional histological lesions (P ranged between 0.0151 and <0.0001). Conclusions: Ki67 evaluation provides quantitative and objective data on squamous epithelium proliferative activity. This marker can be applied in the distinction of endoscopy-negative GERD from healthy controls.