The Utility of Mucin 2 and Caudal-Type Homeobox Transcription Factor 2 Expression in the Diagnosis of Barrett's Esophagus: A Community-Based Study of Wide-Area Transepithelial Sampling and Forceps Biopsies

INTRODUCTION: – The diagnosis of Barrett's esophagus (BE) requires identification of goblet cells in esophageal columnar-lined epithelium. Forceps biopsies (FB) may miss goblet cells because of sampling error. In addition, pathologists may misidentify distended pseudogoblet cells as true goblet cells. Caudal-type homeobox transcription factor 2 (CDX2) and mucin 2 (MUC2) are molecules involved in BE pathogenesis. The utility of CDX2 and MUC2 immunohistochemistry is assessed in the diagnosis of BE.METHODS: – We performed a prospective, community-based registry study of patients with gastroesophageal reflux disease undergoing endoscopy for BE screening. All patients underwent both FB and Wide Area Transepithelial Sampling with 3-Dimensional Computer Analysis (WATS3D). CDX2 and MUC2 immunohistochemistry was performed on WATS3D samples. We assessed concordance between CDX2 and MUC2 staining and goblet cells, on both WATS3D and FB. Operating characteristics of FB for diagnosing BE were calculated using MUC2 positivity and goblet cells on WATS3D as the gold standard.RESULTS: – Of 35, 265 patients enrolled, 11, 040 (31.3%) met endoscopic criteria for BE. Of these, 8, 464 (76.7%) were CDX2+ and 3, 563 (32.3%) were MUC2+. Whereas there was almost perfect concordance between MUC2 positivity and goblet cells on WATS3D, only 65.4% of patients with goblet cells on FB were MUC2+ on WATS3D. When using MUC2+ and goblet cells on WATS3D as the reference standard, FB diagnosed BE with sensitivity of 46.3%, specificity 88.3%, positive predictive value 65.4%, and negative predictive value 77.5%.DISCUSSION: – MUC2 immunohistochemistry may be more sensitive and specific for diagnosing BE than goblet cells by FB. FB misses approximately half of BE when using MUC2/WATS3D as an alternative gold standard. The addition of MUC2 immunohistochemistry may aid in the recognition of BE.