Cathepsin D is a marker of ganglion cell differentiation in the developing and neoplastic human peripheral sympathetic nervous tissues

G. Magro, M. Ruggieri, F. Fraggetta, S. Grasso, G. Viale

Research output: Contribution to journalArticlepeer-review

Abstract

Cathepsin D (CD) is an aspartic proteinase which has been immunolocalised in intestinal ganglion cells of human neonates and adults. The aim of the present study was to define whether CD is a reliable ganglion cell differentiation marker in routinely fixed, paraffin-embedded tissues. For this purpose, we investigated immunohistochemically the expression and distribution of CD in the developing human peripheral sympathetic nervous system (PSNS) and gastroenteric nervous system (GENS), and in childhood neuroblastic tumours (NTs; neuroblastomas, ganglioneuroblastomas and ganglioneuromas), where ganglion cells differentiate from immature neuroblastic cells. During ontogenesis, CD expression is restricted to ganglion cell lineage with a progressively more intense cytoplasmic staining, mirroring the morphological differentiation of ganglion cells with increasing gestational ages. In neoplastic tissues, CD immunoreactivity was restricted to neuroblastic cells showing morphological features of gangliocytic differentiation (differentiating neuroblastomas, ganglioneuroblastomas) as well as to neoplastic ganglion cells (ganglioneuroblastomas, ganglioneuromas). We conclude that CD is a reliable ganglion cell differentiation marker, which can be used routinely to stain developing and mature ganglion cells in formalin-fixed, paraffin-embedded tissues. Furthermore, our results indicate that CD immunoreactivity in childhood NTs recapitulates the changes during normal PSNS development, as previously reported for Bcl-2 oncoprotein, c-ErbB2, insulin-like growth factor 2 and β2-microglobulin. This is consistent with the current view that childhood NTs exhibit gene expression profiles mirroring those occurring during PSNS ontogenesis.

Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalVirchows Archiv
Volume437
Issue number4
Publication statusPublished - 2000

Keywords

  • Cathepsin D
  • Human fetus
  • Neuroblastic tumours
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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