MUCIN GENE-EXPRESSION IN NORMAL, PRENEOPLASTIC, AND NEOPLASTIC HUMAN GASTRIC EPITHELIUM

Mucins synthesized by malignant cells may contribute (via decreased ce llular adhesion and immune recognition) to cancer invasion and metasta ses. Human mucins are derived from a heterogeneous family of genes, la beled MUC1-6. Our aim was to determine the pattern of mucin gene expre ssion in normal, preneoplastic (intestinal metaplasia), and malignant gastric specimens. Probes and antibodies for specific mucin tandem rep eat sequences were used for RNA and immunohistochemical analysis. Norm al stomach mucosa was characterized by expression of MUC1, MUC5, and M UC6 mRNA and immunoreactive protein, without MUC2, MUC3, and MUC4 gene expression. In contrast, high levels of MUC2 and MUC3 mucin mRNA and immunoreactive protein were found in specimens with intestinal metapla sia. Gastric cancers exhibited markedly altered secretory mucin mRNA l evels compared with adjacent normal mucosa, with decreased levels of M UGS and MUC6 mRNA and increased levels of MUC3 and MUC4 mRNA. Overall, immunoreactive MUC1 mucin was detected in 72% of 33 gastric cancers, and secretory mucin core peptides were expressed in 34% (MUC2), 45% (M UC3), 19% (MUC5), and 57% (MUC6) of these specimens. Coexpression of m ultiple (three or more) mucin core proteins occurred in 15 of 25 (60%) advanced (stages III and IV) cancers compared with 1 of 8 (12.5%) ear ly (stages I and II) cancers (P < 0.048). We conclude that human gastr ic epithelium has a unique mucin gene pattern, which becomes markedly altered in preneoplastic and neoplastic specimens. Increased mucin gen e heterogeneity in gastric adenocarcinomas is associated with advanced cancer stage.