Neoplastic Human Gastric Epithelium Mucin Gene Expression in Normal, Preneoplastic, and Updated Version

Mucins synthesized by malignant cells may contribute (via decreased cellular adhesion and immune recognition) to cancer invasion and métas tases. Human mucins are derived from a heterogeneous family of genes, labeled MUCI-6. Our aim was to determine the pattern of mucin gene expression in normal, preneoplastic (intestinal metaplasia), and malignant gastric specimens. Probes and antibodies for specific mucin tandem repeat sequences were used for RNA and immunohistochemical analysis. Normal stomach mucosa was characterized by expression of Miti. MUC5, and MUC6 mRNA and immunoreactive protein, without MUC2, MUC3, and MVC4 gene expression. In contrast, high levels of MUC2 and MUC3 mucin mRNA and immunoreactive protein were found in specimens with intestinal metaplasia. Gastric cancers exhibited markedly altered secre tory mucin mRNA levels compared with adjacent normal mucosa, with decreased levels of MVC5 and Aft/Co mRNA and increased levels of MUC3 and MUC4 mRNA. Overall, immunoreactive MVC1 mucin was detected in 72% of 33 gastric cancers, and secretory mucin core peptides were expressed in 34% (MVC2), 45% (MUC3), 19% (A/Õ/C5), and 57% (MUC6) of these specimens. Coexpression of multiple (three or more) mucin core proteins occurred in 15 of 25 (60%) advanced (stages HI and IV) cancers compared with 1 of 8 (12.5%) early (stages I and II) cancers l /' < 0.048). We conclude that human gastric epithelium has a unique mucin gene pattern, which becomes markedly altered in preneoplastic and neoplastic specimens. Increased mucin gene heterogeneity in gastric adenocarcinomas is associated with advanced cancer stage.