Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett's esophagus

A distinctive type of multilayered epithelium (ME) has been described at th e neo-squamocolumnar junction and within columnar mucosa in patients with B arrett's esophagus (BE). This epithelium has morphologic and ultrastructura l features of both squamous and columnar epithelium. Multilayered epitheliu m may represent an early or intermediate stage of columnar metaplasia: ther efore, we performed this: study to determine the morphologic and biologic c haracteristics of this epithelium and to gain insight into its derivation. Esophageal mucosal biopsies containing ME from 17 patients with BE were eva luated morphologically, stained with a variety of mucin histochemical stain s; and also immunostained with antibodies against cytokeratins (CK) 13 (squ amous epithelium marker); 14 (basal squamous epithelium marker) 7, 8/18, 19 , and 20 (columnar epithelium markers). MIB-1 (proliferation marker): villi n (intestinal brush border protein), and TGF alpha. EGFR, pS2, and hSP (ent eric proliferation/differentiation regulatory peptides). The results were c ompared with normal esophageal squamous epi thelium, normal gastric cardia epithelium, specialized-type intestinal epithelium (BE), and esophageal muc osal and submucosal gland duct epithelium. Multilayered epithelium expresse d a pattern of mucin production (neutral mucin, sialomucin. and sulfomucin in 88%. 100%. and 71% of cases, respectively) and cytokeratin expression (C K 13 and 19 in the basal "squamoid" cells, CK 7. 8/18. 19. and 20 in the su perficial "columnar" cells) similar to that of columnar epithelium in BE. a nd showed a high capacity for cellular proliferation (Ki-67-positive: in 88 % of cases) and differentiation (TGFa, EGFR. pS2 and villin-positive in 100 %. 100%, 93%, and 66% of casts, respectively). The mucosal gland duct epith elium showed a similar phenotypic pattern and. in one case, was seen to giv e rise to ME at the surface of the mucosa. These data provide evidence in s upport of the hypothesis that ME represents an early or intermediate stage in the development of esophageal columnar metaplasia (BE). The mucosal glan d duct epithelium may contain progenitor cells that can give rise to ME.