Expression of the p53 homologue p63 alpha and Delta Np63 alpha in the neoplastic sequence of Barrett's oesophagus: correlation with morphology and p53 protein

Background-While loss of p53 function is a key oncogenic step in human tumo rigenesis, mutations of p53 are generally viewed as late events in the meta plasiadysplasia-adenocarcinoma sequence of Barrett's oesophagus. Recent rep orts of a series of genes (p63, p73, and others) exhibiting close homology to p53 raise the possibility that abnormalities of these p53 family members may exert their influence earlier in the sequence. Aim-Following recent characterisation of expression of p63 and a major isof orm Delta Np63 by generation of an antiserum. that recognises p63 isoforms, but not p53, our aim, was a comparative study of expression of p63 protein and p53 protein in a morphologically well defined biopsy series representa tive of all stages of the metaplasia-dysplasia-carcinoma sequence in Barret t's oesophagus. Methods-A series of 60 biopsy cases representing normal oesophagus through to invasive adenocarcinoma were stained, using immunohistochemistry, with a ntibodies to p63 and p53. All biopsies derived from patients with endoscopi c and histopathological substantiation of a diagnosis. of traditional/class ical Barrett's oesophagus. Results-There was exact concordance in p53 and p63 expression in more advan ced forms of neoplasia, high grade dysplasia, and invasive adenocarcinoma, while p63, but not p53, was detected in the proliferative compartment of so me non-neoplastic oesophageal tissue, in both squamous mucosa and in the no n-neoplastic metaplastic glandular epithelium. Conclusions-In neoplastic Barrett's oesophagus there is upregulation of bot h p63 and p53 while p63 isoforms may well have an important role in epithel ial biology in both non-metaplastic and metaplastic mucosa of the oesophagu s. While abnormalities of p53 function represent an indisputable and critic al element of neoplastic transformation, other closely linked genes and the ir proteins have a role in both the physiology and pathophysiology of the o esophageal mucosa.