Meta-analysis of biomarkers predicting risk of malignant progression in Barrett's oesophagus

BackgroundBarrett's oesophagus is a precursor to the development of oesophageal adenocarcinoma. This study sought to clarify the role of genetic, chromosomal and proliferation biomarkers that have been the subjects of multiple studies through meta-analysis. MethodsMEDLINE, Embase, PubMed and the Cochrane Library were searched for clinical studies assessing the value of p53, p16, Ki-67 and DNA content abnormalities in Barrett's oesophagus. The main outcome measure was the risk of development of high-grade dysplasia (HGD) or oesophageal adenocarcinoma. ResultsSome 102 studies, with 12353 samples, were identified. Mutation (diagnostic odds ratio (DOR) 1091, sensitivity 47 per cent, specificity 92 per cent, positive likelihood ratio (PLR) 471, negative likelihood ratio (NLR) 065, area under the curve (AUC) 0792) and loss (DOR 1616, sensitivity 31 per cent, specificity 98 per cent, PLR 666, NLR 041, AUC 0923) of p53 were found to be superior to the other p53 abnormalities (loss of heterozygosity (LOH) and overexpression). Ki-67 had high sensitivity in identifying high-risk patients (DOR 554, sensitivity 82 per cent, specificity 48 per cent, PLR 159, NLR 042, AUC 0761). Aneuploidy (DOR 1208, sensitivity 53 per cent, specificity 87 per cent, PLR 426, NLR 042, AUC 0846), tetraploidy (DOR 587, sensitivity 46 per cent, specificity 85 per cent, PLR 347, NLR 065, AUC 0793) and loss of Y chromosome (DOR 923, sensitivity 68 per cent, specificity 80 per cent, PLR 267, NLR 049, AUC 0807) also predicted malignant development, but p16 aberrations (hypermethylation, LOH, mutation and loss) failed to demonstrate any advantage over the other biomarkers studied. ConclusionLoss and mutation of p53, and raised level of Ki-67 predicted malignant progression in Barrett's oesophagus. Limited clinical usefulness at present