3’-Sulfated Lewis A is a Biomarker for Metaplastic and Oncogenic Transformation of Several Gastrointestinal Epithelia

Abstract

ABSTRACTIntroductionMultiple previous studies have shown the monoclonal antibody Das-1 (formerly called 7E12H12) specifically recognizes metaplastic and carcinomatous lesions in multiple organs of the gastrointestinal system (e.g. Barrett’s esophagus, intestinal-type metaplasia of the stomach, gastric adenocarcinoma, high-grade pancreatic intraepithelial neoplasm, and pancreatic ductal adenocarcinoma) as well as in other organs (bladder and lung carcinomas). Beyond being a useful biomarker in tissue, mAb Das-1 has recently proven to be more accurate than current paradigms for identifying cysts harboring advanced neoplasia. Though this antibody has been used extensively for clinical, basic science, and translational applications for decades, its epitope has remained elusive.MethodsIn this study, we chemically deglycosylated a standard source of antigen, which resulted in near complete loss of the signal as measured by western blot analysis. The epitope recognized by mAb Das-1 was determined by affinity to a comprehensive glycan array and validated by inhibition of a direct ELISA.ResultsThe epitope recognized by mAb Das-1 is 3’-Sulfo-Lewis A (3’-Sulfo-LeA). 3’-Sulfo-LeA is broadly reexpressed across numerous GI epithelia and elsewhere only after metaplastic and carcinomatous transformation.Discussion3’-Sulfo-LeA is a clinically important antigen that can be detected both intracellularly in tissue using immunohistochemistry and extracellularly in cyst fluid and serum by ELISA. The results open new avenues for tumorigenic risk stratification of various gastrointestinal lesions.