Barrett's esophagus (BE) is the precursor lesion of esophageal adenocarcinoma (EAC). None of the current clinical or endoscopic criteria are able to accurately predict which patients will progress from BE to EAC. Immunohistochemical (IHC) biomarkers can be applied to intact histological morphology and are relatively easy applicable in daily practice. This study aimed to provide a systematic review and meta-analyses of all published studies on IHC biomarkers as predictors of neoplastic progression in BE.
MEDLINE, EMBASE, Web of Science, CENTRAL, Pubmed publisher, and Google scholar were searched. All studies on IHC biomarkers in BE progression were included. Two authors independently extracted data. Meta-analyses were performed for biomarkers studied more than once. Pooled estimates of effect were calculated. If enough studies were present, sensitivity analyses and sub-analyses were performed. Sub-analyses were performed to investigate whether IHC biomarkers had a predictive value independent of the presence of LGD.
IHC biomarkers studied more than once were p53, Cyclin A, Cyclin D, and aspergillus oryzae lectin (AOL). The IHC biomarker investigated most frequently was p53. P53 was included in 12 studies, which contained 2023 patients, amongst which 372 cases. The meta-analyses showed aberrant p53 IHC staining was significantly associated with the risk of neoplastic progression in BE patients with an OR of 4.15 (95% CI 1.96 to 8.81). A sub-analysis stratifying for the presence or absence of LGD showed that aberrant p53 IHC staining was associated with neoplastic progression with an OR of 4.13 (95% CI 2.36 to 7.21). This association was confirmed for both non-dysplastic BE, and BE with low grade dysplasia. Of the other IHC biomarkers, Cyclin A (OR 1.54, 95% CI 0.62 to 3.79), Cyclin D (OR 1.87, 95% CI 0.17 to 20.63), and AOL, only AOL appeared to be able to predict neoplastic progression in BE patients with an OR of 3.04 (95% CI 2.05 to 4.49).
In conclusion, p53 is the most studied IHC biomarker for neoplastic progression in patients with BE. Aberrant p53 IHC is significantly associated with an increased risk of neoplastic progression in BE patients, which appears to be independent of dysplasia grade.
Clinical trial identification
Legal entity responsible for the study
Department of Gastroenterology and Hepatology of the ErasmusMC
All authors have declared no conflicts of interest.