MN antigen expression in normal, preneoplastic, and neoplastic esophagus: A clinicopathological study of a new cancer-associated biomarker

Abstract

Recently, a novel tumor-associated protein, termed MN, has been described in carcinomas of the uterine cervix, where its expression has been shown to be associated with malignant transformation. Because malignant transformation in the esophagus develops through a dysplasia-carcinoma sequence similar to that which occurs in the cervix, this study was performed to evaluate MN expression in normal, preneoplastic, and neoplastic tissues of the esophagus. Esophageal tumor resection specimens from 27 patients (12 squamous cell carcinomas, one multifocal squamous dysplasia, 10 Barrett's-associated adenocarcinomas, two Barrett's esophagus with dysplasia, two adenosquamous carcinomas) were immunohistochemically stained with a monoclonal antibody (clone M75) directed against the MN antigen. The localization of MN antigen, as well as the proportion of positively stained cells, were determined in sections of normal, dysplastic, and carcinomatous tissues. The staining characteristics were correlated with the pathological features of the tumors. Weak intracellular MN expression was detected only in the basal cells of normal squamous epithelium. However, inflamed and reactive squamous epithelium showed increased staining in the basal layer and in the overlying mature squamous cells. MN expression was significantly increased in dysplastic squamous epithelium ( P < .001). All esophageal squamous cell carcinomas (100%) stained positively for MN antigen, where the pattern of staining was predominantly membranous. However, the degree of MN staining did not correlate with any of the pathological features of the tumors. In Barrett's epithelium, MN stained positively in all types of metaplastic cells and showed no difference in dysplastic epithelium. In contrast to squamous cell carcinomas, only 80% of esophageal adenocarcinomas were positive for MN, but the degree of MN expression was inversely correlated with histological tumor differentiation ( P < .015). The results of this study suggest that (1) the tumor-associated MN antigen may play a role in proliferation and regeneration in esophageal squamous epithelium, and (2) loss of MN expression may be related to cancer progression in Barrett's-associated adenocarcinomas.