Mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus

Esophageal carcinoma includes squamous cell carcinoma and Barrett's adenoca rcinoma. The latter usually develops from a premalignant lesion named Barre tt's esophagus. MUC genes are known to be specifically expressed in the nor mal, premalignant and malignant epithelia of various tissues. The aim of th is study was to establish the pattern of MUC gene expression in the esophag eal mucosa under normal conditions, and under pathological conditions such as squamous cell carcinoma, Barrett's esophagus and adenocarcinoma. Samples of esophageal control mucosa, metaplastic and malignant tissues were obtai ned from 40 patients undergoing esophagectomy for squamous cell carcinoma ( n = 17), or Barrett's esophagus with adenocarcinoma (n = 23). In situ hybri dization and northern blot were used with probes specific for the MUC1, MUC 2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7 genes to assess their expressio n in these samples. Submucosal glands of control esophageal mucosa expresse d MUC5B, whereas MUC1 and MUC4 were found in both control epithelium and sq uamous cell carcinoma. MUC4 expression correlated with squamous cell differ entiation. Barrett's adenocarcinoma exhibited various patterns of MUC gene expression, the strongest being in the well-differentiated mucinous adenoca rcinomas. Barrett's metaplasia was also associated with a specific MUC gene expression pattern, since the gastric apomucin mRNAs, MUC5AC and MUC6, wer e expressed in gastric metaplasia, and the intestinal apomucin mRNAs, MUC3, MUC4 and mostly MUC2, in intestinal metaplasia. Residual expression of gas tric apomucin mRNAs was found in intestinal metaplasia. From these results, we conclude that MUC genes can be considered reliable phenotypic markers o f the esophageal cell differentiation, thus providing new insight into the development of Barrett's esophagus. Int. J. Cancer 88:856-861, 2000. (C) 20 00 Wiley-Liss, Inc.