Beta-Catenin and c-Met Provide a Useful Panel To Predict the Development of Dysplasia in Barrett's Esophagus
Xuefeng Zhang, Maria Westerhoff, John Hart. University of Chicago, Chicago, IL; University of Washington, Seattle, WA
Background: Barrett's esophagus (BE) is the only known precursor lesion for esophageal adenocarcinoma (EAC). The BE-dysplasia-EAC sequence is well established, but the risk of progression to EAC is low. Therefore, biomarkers to stratify risk of progression would be helpful to optimize surveillance and management strategies. Abnormal expression of c-met, p16, and beta-catenin is frequent in dysplastic BE mucosa, but has not been studied extensively in non-dysplastic BE. The use of these markers to predict the future development of dysplasia is the focus of this study.
Design: A surgical pathology database was searched from 1990 to 2008 to identify patients with an initial biopsy revealing non-dysplastic BE who during follow-up developed dysplasia. Among a group of 258 new BE patients, 13 later developed dysplasia (dysplasia group [DG]). For each case in the DG, 1 age and sex matched control was selected from the 245 BE patients who never developed dysplasia. Immunostains for c-met, beta-catenin, and p16 were performed on the initial biopsies. The results were interpreted by two pathologists independently in a masked manner.
Results: There was no significant difference in the number of biopsies and follow-up duration between the DG and the control group. The average time interval between the initial biopsy and the biopsy showing dysplasia was 4.9 years, with 5/13 cases developing dysplasia within 1 year. Abnormal cytoplasmic beta-catenin expression was present in 12/13 of the cases in the DG and in 3/13 controls. Cytoplasmic c-met immunoreactivity was seen in 9/13 DG cases and in 5/13 controls. All the biopsies in the DG and 6/13 of the controls exhibited positivity for at least 1 of these 2 markers. Immunoreactivity for both markers was seen in 8/13 DG cases and 1/13 controls. Sensitivity, specificity, positive/negative predictive value, and the odds ratio of the 2 markers were summarized in Table 1. There was no difference in p16 expression between the DG and control group.
|Sensitivity (%)||Specificity (%)||PPV (%)||NPV (%)||OR|