Expression of p53-related protein p63 in the gastrointestinal tract and inesophageal metaplastic and neoplastic disorders

p63 is a p53-related DNA-binding protein that helps regulate differentiatio n and proliferation in epithelial progenitor cells. Its expression has neve r been evaluated in the human gastrointestinal tract. The aim of this study was to evaluate the expression of p63 in the esophagus and related metapla stic and neoplastic disorders to gain insight into the pathogenesis of thes e processes. Of particular interest was the expression of p63 in Barrett es ophagus (BE) and in BE-associated multilayered epithelium. Multilayered epi thelium has been postulated to represent an early precursor to the developm ent of BE primarily because it shares morphologic and immunophenotypic feat ures of both squamous and columnar epithelium, and has been shown prospecti vely to be highly associated with BE. Routinely processed mucosal biopsy or resection specimens that contained normal esophageal squamous epithelium ( n = 20), squamous dysplasia (n = 4), squamous cell carcinoma (n = 7), BE (n = 10), BE-associated multilayered epithelium (n = 13), esophageal mucosal gland ducts (n = 10), BE-associated dysplasia (n = 12), and BE-associated a denocarcinoma (n = 7) were immunostained for p63 to determine the extent an d location of staining. p63 staining was compared with the staining pattern s observed for p53, Ki 67 (proliferation marker), and cytokeratins (CKs) 13 (squamous marker), 14 (basal squamous marker), 8/18 (columnar marker), and 19 (basal/ columnar marker). Expression of p63 messenger RNA (mRNA) isofor ms was also analyzed by reverse-transcription polymerase chain reaction of freshly isolated tissues. In the normal esophagus, p63 was expressed in the basal and suprabasal layers of the squamous epithelium and in basal cells that line the mucosal gland ducts but was negative in all other epithelia o f the gastrointestinal tract, including the stomach, small intestine, and c olon. Similarly, p63 was not expressed in BE, but it, was present in the ba sal laver of multilayered epithelium in 9 of 13 cases (69%). p63-positive c ells in multilayered epithelium and in the mucosal gland duct epithelium we re positive for CK8/18 (100%) and CK13 (67% and 30%, respectively) and nega tive for CK14 (0%), in contrast to p63-positive cells in squamous epitheliu m, which were positive for CK14 and CK13 (100%) but negative for CK8/18. In neoplastic tissues, p63 was diffusely expressed in all cases of esophageal squamous cell dysplasia and carcinoma but was negative in all cases of eso phageal and colorectal adenocarcinoma. The DeltaN isoform of p63 mRNA predo minated in all benign and neoplastic squamous tissues examined. p63 may rep resent a marker of 2 distinct epithelial progenitor cells (basal squamous e pithelium mid gland duct epithelium) in the esophagus. P63 is upregulated i n squamous neoplastic conditions and in this manner may play a role in squa mous carcinogenesis. These data also indicate that multilayered epithelium is phenotypically similar to, and may share a lineage relationship with, mu cosal gland duct epithelium. HUM PATHOL 32:1157-1165. Copyright (C), 2001 b y W.B. Saunders Company.