title: Neuroblastoma after childhood: prognostic relevance of segmental chromosome aberrations, ATRX protein status, and immune cell infiltration.
abstract: Neuroblastoma (NB) is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked (ATRX) protein expression, and the presence of tumor-associated inflammatory cells. Thirty-one NB patients older than 10 years who were included in the Spanish NB Registry were considered for the current study; seven young and middle-aged adult patients (range 18-60 years) formed part of the cohort. We performed single nucleotide polymorphism arrays, immunohistochemistry for immune markers (CD4, CD8, CD20, CD11b, CD11c, and CD68), and ATRX protein expression. Assorted genetic profiles were found with a predominant presence of a segmental chromosome aberration (SCA) profile. Preadolescent and adolescent NB tumors showed a higher number of SCA, including 17q gain and 11q deletion. There was also a marked infiltration of immune cells, mainly high and heterogeneous, in young and middle-aged adult tumors. ATRX negative expression was present in the tumors. The characteristics of preadolescent, adolescent, young adult, and middle-aged adult NB tumors are different, not only from childhood NB tumors but also from each other. Similar examinations of a larger number of such tumor tissues from cooperative groups should lead to a better older age-dependent tumor pattern and to innovative, individual risk-adapted therapeutic approaches for these patients.
authors: Pathology Department, Medical School, University of Valencia, INCLIVA, Valencia, Spain; Medical Research Foundation INCLIVA, Hospital Clínico, INCLIVA, Valencia, Spain.
authors: Ana P
authors: AP
authors: Berbegall
authors: Pathology Department, Medical School, University of Valencia, INCLIVA, Valencia, Spain.
authors: Eva
authors: E
authors: Villamón
authors: Pathology Department, Medical School, University of Valencia, INCLIVA, Valencia, Spain; Medical Research Foundation INCLIVA, Hospital Clínico, INCLIVA, Valencia, Spain.
authors: Irene
authors: I
authors: Tadeo
authors: Department of Clinical Genetics, Göteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Tommy
authors: T
authors: Martinsson
authors: Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Adela
authors: A
authors: Cañete
authors: Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Victoria
authors: V
authors: Castel
authors: Pathology Department, Medical School, University of Valencia, INCLIVA, Valencia, Spain.
authors: Samuel
authors: S
authors: Navarro
authors: Pathology Department, Medical School, University of Valencia, INCLIVA, Valencia, Spain. Electronic address: rosa.noguera@uv.es.
authors: Rosa
authors: R
authors: Noguera
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations; D004265:DNA Helicases / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D009687:Nuclear Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012042:Registries; D013030:Spain / Q000453:epidemiology; D000075924:X-linked Nuclear Protein; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein