Please cite this article in press as: Magro G, et al. Cyclin D1 in human neuroblastic tumors recapitulates its developmental expression: An immunohistochemical study. Acta Histochemica (2015), http://dx.doi.org/10.1016/j.acthis.2015.01.006 ARTICLE IN PRESS G Model ACTHIS-50959; No. of Pages 10 Acta Histochemica xxx (2015) xxx–xxx Contents lists available at ScienceDirect Acta Histochemica jo ur nal homepage: www.elsevier.de/acthis Cyclin D1 in human neuroblastic tumors recapitulates its developmental expression: An immunohistochemical study Gaetano Magro a,∗ , Lucia Salvatorelli a , Andrea Di Cataldo c , Giuseppe Musumeci b , Graziana Spoto a , Rosalba Parenti d a Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, AziendaOspedaliero-Universitaria “Policlinico-Vittorio Emanuele”, Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy b Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy c Department of Paediatric Haematology and Oncology, University of Catania, Catania, Italy d Department of Biomedical and Biotechnological Sciences, Section of Physiology, School of Medicine, University of Catania, Catania, Italy a r t i c l e i n f o Article history: Received 10 December 2014 Received in revised form 21 January 2015 Accepted 28 January 2015 Available online xxx Keywords: Cyclin D1 Immunohistochemistry Human fetus Sympathetic nervous system Neuroblastic tumors a b s t r a c t The protein cyclin D1 (CD1), which belongs to a family of proteins functioning as regulators of CDKs (cyclin-dependent kinases) throughout the cell cycle, has been immunohistochemically detected in a wide variety of human malignant tumors. The aim of the present study was to investigate immunohis- tochemically the expression and distribution of CD1 in the developing human peripheral sympathetic nervous system (PSNS) and in childhood peripheral neuroblastic tumors (neuroblastomas, ganglioneu- roblastomas, and ganglioneuromas). The above mentioned fetal and neoplastic tissues represent an in vivo model in which undifferentiated neuroblastic cells undergo ganglion cell differentiation. Dur- ing development, a strong nuclear expression of CD1 was restricted to neuroblasts, disappearing progressively from the maturing ganglion cells with increasing gestational age. In neoplastic tissues, CD1 immunoreactivity was restricted to neuroblastic cell component of all neuroblastomas and gan- glioneuroblastomas, whereas it was absent or only focally detectable in maturing/mature ganglion cell component of differentiating neuroblastomas, ganglioneuroblastomas, and ganglioneuromas. We con- clude that CD1 is a reliable marker, which can be used routinely to stain neuroblastic cells in both developing and neoplastic tissues. Furthermore, our results indicate that CD1 expression in childhood peripheral neuroblastic tumors recapitulates the changes during normal development of PSNS, as pre- viously reported for Bcl-2 oncoprotein, c-ErbB2, insulin-like growth factor 2, -2-microglobulin, and cathepsin D. This is consistent with the current view that childhood peripheral neuroblastic tumors exhibit gene expression profiles mirroring those occurring during PSNS development. © 2015 Elsevier GmbH. All rights reserved. Introduction The protein cyclin D1 (CD1), encoded by the CCND1 gene, belongs to the highly conserved cyclin family, whose members function as regulators of CDKs (cyclin-dependent kinase) through- out the cell cycle (Motokura et al., 1991; Lew et al., 1991; Kato et al., 1993; Weinberg, 1995; Lundberg and Weinberg, 1998). CD1 serves as a key sensor and integrator of extracellular signals of cells to promote progression through the G1–S phase of the cell Abbreviations: CD1, cyclin D1; PSNS, peripheral sympathetic nervous system. ∗ Corresponding author. Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, Azienda Ospedaliero-Universitaria ¨¨Policlinico-Vittorio Emanuele¨, Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy. E-mail address: g.magro@unict.it (G. Magro). cycle, playing several biological roles in promoting cellular prolif- eration/differentiation, apoptosis/survival, migration, metabolism, and neuronal regeneration (Fu et al., 2004). In humans, only a few data are available about the developmental expression profile of CD1, excepting for its overexpression in proliferative cardiomy- ocytes during normal heart development (Kim et al., 1998; Ahuja et al., 2007; Hotchkiss et al., 2012). On the contrary, CD1 over- expression has been found to occur early during tumorigenesis, suggesting it may serve as a drive oncogene through its cell-cycle regulating function (Fu et al., 2004). In this regard, CD1 expression has been reported in a wide variety of human tumors, including those of parathyroid, breast, esophagus, bladder, lung, prostate, colon, as well as in lymphomas and melanomas (Motokura and Arnold, 1993; Peters, 1994; Hall and Peters, 1996; Arnold et al., 2002; Diehl, 2002; Fu et al., 2004; Sutherland and Musgrove, 2004; Knudsen et al., 2006; Musgrove, 2006; Alao, 2007; Casimiro et al., 2012). However, only a few information is available on CD1 http://dx.doi.org/10.1016/j.acthis.2015.01.006 0065-1281/© 2015 Elsevier GmbH. All rights reserved.