Biomarkers of oesophageal neoplasia

Background. Symptomatic oesophageal cancer is usually advanced and terminates fatally. There is a need for biomarkers to help pathologists recognise patients at increased risk of squamous and glandular oesophageal cancers (in the case of Barrett's oesophagus). The work described in this thesis looks at four topics: cytokeratin 7 and 20 phenotypes in Barrett's intestinal metaplasia; the distribution of cardiac, cardio-oxyntic and 'specialised' intestinal-type Barrett's mucosa in relation to glandular dysplasia; dysregulated expression of the proliferation marker Ki67 and the DNA replication-licensing proteins Mcm2 and Mcm5 in glandular and squamous dysplasia; and relates different types of complete (type I) and incomplete (types IIA/IIB) intestinal metaplasia to dysplasia/neoplasia in Barrett's esophagus. Results. Cytokeratin 7 and 20 phenotypes are complex and variable, so likely clinical utility is not immediately obvious. The ubiquitous presence of intestinal metaplasia (IM) in Barrett's mucosa is confirmed, and a very strong association of IM with dysplasia. A positive association exists between dysplasia and type IIB intestinal metaplasia, and an even stronger negative association with type I intestinal metaplasia. This identifies a possibility that robust markers of (complete) small intestinal metaplasia may be associated with low dysplasia risk in Barrett's oesophagus, whereas a potentially colonic phenotype (type IIB IM) is associated with greater risk. Over-expression of the cell-proliferation related antigen Ki67 and the DNA replication licensing proteins Mcm2 and Mcm5 in the differentiated surface compartment of squamous oesophageal epithelium and Barrett's mucosa confirm the Mem proteins are promising markers of oesophageal dysplasia meriting further evaluation, e.g. in the field of non-endoscopic oesophageal cytology