CD44 ISOFORM EXPRESSION IN THE DIFFUSE NEUROENDOCRINE SYSTEM .1. NORMAL-CELLS AND HYPERPLASIA

Isoforms of the transmembrane glycoprotein CD44, which are generated b y alternative splicing of nine variant exons, have been implicated in tumor cell adhesion, invasion and metastatic spread and may be indicat ors of the degree of tumor differentiation. Since little is known abou t the distribution of CD44 in non-neoplastic neuroendocrine cell types , we systematically investigated 42 samples of tissue from different o rgans, including the pituitary gland, thyroid, parathyroid, adrenal gl and, lung, pancreas, stomach, duodenum, jejunum, ileum, appendix, and colon, immunohistochemically for the expression of CD44 standard and v ariant exon-encoded gene products (CD44v3, v4, v5, v6, v9). Furthermor e, double immunolabeling for CD44 and a variety of peptide hormones wa s applied to characterize the different neuroendocrine cell types. Our results show that neuroendocrine cells derived from the neuroectoderm lack CD44 immunoreactivity. However, those originated from the endode rm exhibit a variable CD44 immunostaining which is related to their an atomical localization and the degree of differentiation irrespective o f the hormone produced. Furthermore, we demonstrate that CD44 positive neuroendocrine cells predominantly express CD44 isoforms of the epith elial type and that hyperplastic clusters of neuroendocrine cells of p ancreatic ducts express CD44 most probably as a sign of dedifferentiat ion.