32/67-kD laminin receptor expression in human colonic neoplasia: Elevated transcript levels correlate with the degree of epithelial dysplasia

OBJECTIVE: The 32/67-kD laminin receptor is thought to be involved in tumor cell migration and metastasis formation, and enhanced expression was observed in human colorectal carcinoma. Our objective was to investigate further the expression of the 32/67-kD laminin receptor RNA in human colonic carcinogenesis. METHODS: We obtained sections of human colonic tissues in various stages of malignant transformation and analyzed them by in situ hybridization. RESULTS: Normal colonic mucosa displayed a gradient between crypt base and surface epithelium with lowest receptor RNA levels in superficial epithelial cells. Increased laminin receptor RNA expression was observed in epithelial cells of adenomas with positive correlation between transcript levels and the degree of epithelial dysplasia. At variance with published results, we did not observe significant differences in 32/67-kD laminin receptor transcripts between adenomas with high-grade dysplasia and invasive adenocarcinoma. However, adenocarcinoma metastases displayed significantly higher laminin receptor RNA levels than high-grade adenomas and primary carcinomas. CONCLUSIONS: We propose a two-step mechanism which controls first, upregulation of laminin receptor RNA before the acquisition of an invasive phenotype in dysplastic epithelial cells, and second, a further upregulation in metastatic cells during the adenoma-carcinoma sequence of the colon. (C) 1999 by Am. Coll. of Gastroenterology.