A search for molecular biomarkers in gastro-intestinal cancer

Barrett’s esophagus (BE) is a metaplastic lesion of the esophagus caused by a chronic bile and acid reflux that has a relatively low but still significant risk to develop through various dysplasia stages into esophageal adenocarcinoma. Currently the main predictive measure in BE is histo-pathological staging of random esophageal biopsies taken during endoscopic surveillance, with a diagnosis of dysplasia indicating a higher risk of cancer development. Histo-pathological diagnoses have shown inter-observer variation however and lesions might also be missed. Research is being done into the use of biomarkers to improve this risk prediction and for molecular insight into BE. In this thesis we have looked into the value of a number of biomarkers in BE disease management, such as techniques assessing the status of the tumor suppressor p53, MMP production as an in vivo endoscopic aid and phosphorylation of the Retinoblastoma protein in esophageal adenocarcinoma to gain insight in possible treatment opportunities. Separately, we also investigated the SATB1 protein as a biomarker for poor outcome in sporadic colorectal cancer, a disease which has already shown some useful biomarker application. This thesis shows that biomarkers might indeed play a role in aiding disease management of gastro-intestinal cancers. However, for a truly effective application, multiple biomarkers will likely have to be combined in a single test to cover all patients at risk. For instance, combining p53 abnormalities as detected by immunohistochemistry and FISH leads to a significant prediction of EAC progression. And MMP activity could aid in the diagnosis of dysplastic lesions in BE.