Proliferating cell nuclear antigen in oesophageal diseases; correlation with transforming growth factor alpha expression

Abstract

This study was designed to correlate mucosal proliferation in Barrett's oesophagus with expression of a growth promoting peptide, transforming growth factor alpha (TGFα). Oesophageal mucosa was studied from 50 patients with oesophageal disease who had been treated by oesophagectomy. Histological analysis showed a range of oesophageal pathology - 18 patients had gastric type Barrett's mucosa, 18 had intestinal type Barrett's mucosa, and 14 had oesophageal adenocarcinomas. Sections were stained immunohistochemically for proliferating cell nuclear antigen (PCNA) (an index of cellular proliferation) and TGFα. PCNA immunostaining was seen mainly in the basal cells of the neck/foveolar epithelial compartment of the glands in Barrett's oesophagus. However, in mucosa with high grade dysplasia, the proliferative compartment extended upwards into the superficial glands. At least 2000 cells were counted in each patient to determine the proportion with PCNA immunoreactivity (PCNA labelling index). The labelling index was highest in adenocarcinoma (25%) and in Barrett's intestinal type mucosa with high grade dysplasia (26%) compared with intestinal type mucosa with no significant dysplasia (20%) and Barrett's gastric type mucosa (12%). There was a significant positive correlation between PCNA labelling indices and TGFα expression in Barrett's mucosa (p < 0.01). In glands showing high grade dysplasia, TGFα immunoreactivity was seen in the same regions of the glands as PCNA immunoreactivity, indicating the possibility of involvement of TGFα in (pre) neoplastic proliferation in Barrett's oesophagus.