Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression

PCNA and esophagin have been implicated in the multistep process of carcinogenesis, but simultaneous characterization of these proteins in the early stages of esophageal neoplastic progression has yet to be undertaken. In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principally in their cell membrane portions. PCNA, in contrast, stains the nuclei of cells in the parabasal and basal layers. We examined 201 regions from 47 patients that represented different stages of esophageal neoplasia, comprising 34 areas of normal mucosa, 18 of dysplasia in squamous epithelium (DYS/SC), 39 squamous cell carcinoma (SCCA), 29 areas of Barrett's esophagus, 48 of Barrett's dysplasia (DYS/BAR) and 33 areas of adenocarcinoma (AC). The immunostaining patterns of esophagin and PCNA were evaluated and graded for level of expression. There was loss of esophagin expression in the high- and low-grade dysplasias compared to normal epithelia. In the squamous dysplasias, there was more intense staining (of esophagin in the atypical nuclei and superficial squamous epithelial cells than in the basal cells. PCNA staining was increased in intensity in the high-grade dysplasias relative to normal basal layer cells. Combined analysis of esophagin and PCNA appears to reveal an inverse relationship between proliferation and differentiation during esophageal neoplastic progression. Moreover, this combined staining approach also offers promise for detecting esophageal cancer in early, precancerous stages. (C) 2004 Wiley-Liss, Inc.