Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation

Aims: Changes in the histochemical characteristics of the surface epithelia l mucins is the hallmark of Barrett's metaplasia. The study investigated th e pattern of expression of MUC1 and MUC2 mucin gene products in Barrett's m etaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential. Methods and results: Tissue sections from 51 patients with Barrett's intest inal metaplasia, nine with dysplasia (three indefinite) and 28 resected ade nocarcinomas were stained with monoclonal antibodies to MUC1 and MUC2. The majority of the patients were men (70/88, 80%) who were treated over a peri od of 3 years. None of the patients with dysplasia or carcinoma were under surveillance at the time of presentation. All 51 biopsies with Barrett's me taplasia expressed MUC2 and MUC1 was consistently absent. Neither MUC1 or M UC2 were expressed in the dysplastic epithelium whether in its pure form (6 /6) or when associated with carcinoma (26/28) (P < 0.005). Three biopsies w hich were initially classified as high-grade dysplasia expressed MUC1 and t hese turned out to be carcinomas on further investigations. MUC1 was also e xpressed in 12/28 (43%) of the adenocarcinomas and majority of these were p oorly differentiated stage 3 tumours (P < 0.05). MUC2 was only positive in mucin-secreting carcinomas (4/28; 14%) irrespective of the tumour stage. Conclusion: Despite the large number of patients with Barrett's metaplasia and carcinoma, very few patients presented with dysplasia, implying that Ba rrett's oesophagus is a silent disease in the community presenting late as carcinoma. The study has demonstrated aberrant expression of MUC2 (an intes tinal mucin) in Barrett's metaplasia and this expression is lost when the c ells become dysplastic. The lack of MUC1 in dysplastic epithelium and its e xpression in carcinoma could be utilized as a marker which could differenti ate dysplasia from carcinoma in mucosal biopsies. Furthermore, expression o f MUC1 in advanced stage oesophageal cancers (as in breast cancer) suggests an unfavourable prognosis.