title: Cyclin D1 is a useful marker for soft tissue Ewing's sarcoma/peripheral Primitive Neuroectodermal Tumor in children and adolescents: A comparative immunohistochemical study with rhabdomyosarcoma.
abstract: Cyclin D1 amplification and/or overexpression contribute to the loss of the regulatory circuits that govern G1-S transition phase of the cell cycle, playing pivotal roles in different human malignant tumors, including breast, colon, prostate cancer, lymphoma, melanoma and neuroblastoma. In vitro studies have shown that cyclin D1 is overexpressed in Ewing's sarcoma (EWS)/peripheral Primitive Neuroectodermal Tumor (pPNET), but not in rhabdomyosarcoma cell lines. Only a few immunohistochemical studies are available on cyclin D1 expression in EWS/pPNET, which confirmed its expression only in a limited number of cases. The aim of the present study was a comparative immunohistochemical analysis of the expression and distribution of cyclin D1 in a large series of pediatric/adolescent soft tissue EWS/pPNETs and rhabdomyosarcomas (both embryonal and alveolar subtypes) to assess its potential usefulness in their differential diagnosis. Notably cyclin D1 was strongly and diffusely expressed in all cases (20/20) of EWS/pPNET, while it was lacked in all cases (15/15) of rhabdomyosarcomas. Immunohistochemical overexpression of cyclin D1 in EWS/pPNET is a novel finding which could be exploitable as a diagnostic immunomarker for this tumor. Although highly sensitive, cyclin D1 is not specific for EWS/pPNET, and thus it should not be evaluated alone but in the context of a wide immunohistochemical panel. Accordingly, we first emphasize that when pathologists are dealing with a small round blue cell tumor of soft tissues in pediatric/adolescent patients, a strong and diffuse nuclear expression of cyclin D1 is of complementary diagnostic value to CD99 and FLI-1 in confirming diagnosis of EWS/pPNET and in ruling out rhabdomyosarcoma.
authors.affiliation: 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. Electronic address: g.magro@unict.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
authors.affiliation: Anatomic Pathology Section, "Ospedale Guzzardi", Vittoria, Ragusa, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Brancato
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.affiliation: Department of Pathology, Anatomic Pathology Section, University of Padova, Padova, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Alaggio
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of Physiology, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Parenti
authors.affiliation: 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.
authors.forename: Lucia
authors.initials: L
authors.lastname: Salvatorelli
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019938:Cyclin D1 / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017599:Neuroectodermal Tumors / Q000378:metabolism* / Q000473:pathology; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1
keywords: Cyclin D1; Differential diagnosis; Ewing’s sarcoma/peripheral Primitive Neuroectodermal Tumor; Immunohistochemistry; Rhabdomyosarcoma