Expression of CD44 isoforms in normal human liver and also in regenerative and neoplastic liver changes

CD44 is a transmembrane glycoprotein of which a large number of isoforms exist. There is evidence, mostly from experimental systems, that isoforms of CD44 generated by alternative splicing of ten variant exons are involved in tumor invasion and metastasis formation. We have evaluated the expression of CD44 standard (CD44s) and variant exons (CD44v) encoded gene products in formalin-fixed and paraffin-embedded human liver specimens, using an immunohistochemical protocol with microwave-based antigen-retrieval and signal amplification. Tissue sections from normal, regenerative and neoplastic liver were studied. Our results indicate that: 1. in normal liver, both, hepatocytes and bile duct epithelia lacked detectable CD44s and CD44v containing isoforms; 2. most cirrhotic liver specimens were unreactive. Some regenerative nodules showed a focal weak positivity for CD44v5 and v9. Most proliferating bile ductules were weakly stained for CD44v9 and some of them also for v5 and v6; 3. most hepatocellular carcinomas displayed a heterogeneous staining of varying intensity for CD44v5, v6, v9 and CD44s. In a few tumors a weak staining for CD44v3 and v4 was also present. Furthermore, there was a tendency to an increased staining intensity of CD44 isoforms with decreasing differentiation; 4. cholangiocarcinomas showed a high expression of CD44s, v3, v5, v6 and v9 containing isoforms. We conclude that neoplastic transformation of hepatocytes and bile duct epithelia is associated with qualitative and quantitative changes in the expression of some CD44 variant exons encoded products. The clinical implications of these findings remain to be determined in a large series of patients.