Expression of resistin-like molecule beta in Barrett's esophagus: a novel biomarker for metaplastic epithelium

The formation of goblet cells characterizes the intestinal metaplasia of Barrett's esophagus (BE). Hematoxylin-eosin (HE) staining may fail to show intestinal metaplasia in BE, and PAS-Alcian Blue may present difficulties of interpretation due to its more heterogeneous staining. Recent evidence indicates that expression of resistin-like molecule beta (RELMbeta), a goblet cell-specific protein, is uniquely restricted to intestinal epithelium. However, it still remains largely unknown whether RELMbeta can be served as a biomarker for metaplastic epithelium of BE. In this study, 104 biopsy specimens of the distal esophagus from 88 suspected BE patients were collected, including 56 suspected intestinal metaplasia, 26 gastric type mucosa, and 22 squamous epithelium. We evaluated the RELMbeta expression in these biopsy specimens, and compared with those of CDX-2 immunostaining and PAS-Alcian Blue staining (pH 2.5). Of the suspected intestinal metaplasia specimens, 46 presented intestinal-type goblet cells and were immunostaining positive for RELMbeta and CDX-2, the remaining ten possessed only goblet cell mimickers and were not reactive with RELMbeta and CDX-2. Of the gastric-type mucosa specimens, none reacted with either RELMbeta or CDX-2. Moreover, the squamous epithelium was not reactive with RELMbeta and CDX-2. Acid mucin was present in goblet cells in all cases of BE and columnar cells in ten gastric specimens. In addition, the reactivity of RELMbeta was enhanced in six BE specimens with dysplasia. These results provide evidence that RELMbeta protein may be a novel biomarker to distinguish the intestinal-type goblet cells and goblet cell mimickers, and useful in the correct diagnosis of BE.