Usefulness of histopathological markers in diagnosing Barrett's intraepithelial neoplasia (dysplasia)

The incidence of oesophageal adenocarcinoma has significantly increased in Europe over the last 30 years. The progression from normal mucosa to adenocarcinoma has been associated with genetic and morphological traits regrouped under the term "intra- epithelial neoplasia" (IEN) according to the Vienna classification. The early detection of such lesions represents the first step in the identification of high-risk patients. The morphological criteria of IEN are the gold standard to identify such patients. Firstly described by Riddell et al in 1983, IEN is based on mor- phological criteria including both cytological and architectural alterations and is classified into different stages of severity. However, large studies have clearly demonstrated the lack of repro- ducibility, with large inter-individual discrepancies for both dis- crete and severe lesions. Discrepancies between high grade IEN and adenocarcinoma can be minimized by using the Vienna classification, which groups both of these lesions under the "stage IV". Discrepancies between low-grade IEN and uncertain lesions remain too important. Erroneous and overstated diagnosis of low grade IEN induces an unnecessary follow-up of patients with obvi- ous psychological and economic consequences. Recent studies have demonstrated that the reading of the slides by 2 to 3 gastrointesti- nal (GI) pathologists significantly decreases interpretation mis- takes. Because of these interpretation problems, scientists have looked for non-morphological criteria to confirm the pre-cancerous state. The current PubMed literature proposes many putative biomark- ers. However, none of these has been correctly validated in large prospective case-control studies, which hampers their use in clini- cal routine. DNA quantification by flux cytometry and morphometry repre- sent alternative methods of documenting IEN but these techniques are complex and expensive. The use of the proliferation marker Ki67 needs deep sampling with correct orientation and standard- ized cell counting. P504 S has been studied in Barrett's disease and might be a novel tool. The only promising tool thus far is the over- expression of p53 as shown in prospective studies demonstrating a nice correlation with clinical evolution and is easy to use in clinical routine. (Acta gastroenterol. belg., 2009, 72, 425-432)