title: Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms.
abstract: Atypical teratoid/rhabdoid tumor (AT/RT) may be misdiagnosed as primitive neuroectodermal tumor/medulloblastoma (PNET) and occasionally as other tumors. Molecular genetic analysis of AT/RT demonstrates deletion and mutation of the hSNF5/INI1 gene in most cases, with decreased or absent expression at the RNA or protein level. Immunohistochemistry with an antibody to INI1 was performed to determine whether this would be a sensitive and specific means of assessing INI1 loss in pediatric brain tumors. Fifty-three tumors consisting of 20 AT/RTs, 10 PNETs, and 23 other central nervous system tumors were examined. No nuclear staining was found in all 20 AT/RTs. Most other central nervous system tumors demonstrated nuclear staining. Eight cases in which classification as AT/RT or PNET was difficult were also examined. Seven cases had no chromosome 22 deletion or INI1 mutation; INI1 antibody showed nuclear staining in these cases. One case was a recurrent tumor with features consistent with an AT/RT. INI1 immunostaining was negative in this case, and a mutation in INI1 was subsequently identified. Immunohistochemical staining with an INI1 antibody correlates with molecular findings in AT/RT and may be useful in confirming the histologic diagnosis. INI1 immunostaining may have particular utility in the analysis of tumors with indeterminate histologic features or atypical immunophenotypic profiles.
authors.affiliation: Department of Pathology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Judkins
authors.forename: Joanne
authors.initials: J
authors.lastname: Mauger
authors.forename: As
authors.initials: A
authors.lastname: Ht
authors.forename: Lucy B
authors.initials: LB
authors.lastname: Rorke
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D009154:Mutation; D018242:Neuroectodermal Tumors, Primitive / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein; D013724:Teratoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors