title: Immunohistochemical analysis of INI1 protein in malignant pediatric CNS tumors: Lack of INI1 in atypical teratoid/rhabdoid tumors and in a fraction of primitive neuroectodermal tumors without rhabdoid phenotype.
abstract: Immunohistochemical lack of nuclear INI1 protein expression has been recently described as characteristic finding in atypical teratoid/rhabdoid tumors (AT/RTs), and has been suggested as useful marker to distinguish AT/RTs from other malignant pediatric central nervous system (CNS) tumors. In this study, we examined a large series of malignant pediatric CNS tumors to determine the immunohistochemical expression of INI1 protein in different malignant pediatric tumor entities. Archival paraffin-embedded biopsy specimens of 289 malignant pediatric CNS tumors including medulloblastomas, supratentorial primitive neuroectodermal tumors, glioblastomas, anaplastic astrocytomas, anaplastic ependymomas, choroid plexus carcinomas, germ cell tumors, and AT/RTs were analyzed immunohistochemically for expression of nuclear INI1 protein. Positive INI1 staining was observed in 263 tumors. Lack of INI1 protein was detectable in 26 tumors. Seventeen of the 26 tumors showed morphologically characteristic features of AT/RTs, whereas 9 embryonal tumors did not display rhabdoid features. Tumors without rhabdoid phenotype but lack of INI1 showed an aggressive clinical course and poor response to conventional treatment regimens. In summary, immunohistochemical expression of INI1 protein is lacking in tumors displaying characteristic morphologic features of AT/RT. Furthermore, a certain number of embryonal tumors without rhabdoid features but lack of INI1 protein and aggressive biologic behavior can be detected. We conclude that INI1 protein analysis should be routinely performed in all malignant pediatric embryonal CNS tumors to detect cases with lack of INI1 protein, because patients with these tumors are likely to benefit from intensified treatment.
authors.affiliation: Institute of Neurology, Medical University Vienna, Vienna, Austria. christine.haberler@meduniwien.ac.at
authors.forename: Christine
authors.initials: C
authors.lastname: Haberler
authors.forename: Ute
authors.initials: U
authors.lastname: Laggner
authors.forename: Irene
authors.initials: I
authors.lastname: Slavc
authors.forename: Thomas
authors.initials: T
authors.lastname: Czech
authors.forename: Inge M
authors.initials: IM
authors.lastname: Ambros
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018335:Rhabdoid Tumor / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000071796:SMARCB1 Protein; D016019:Survival Analysis; D013724:Teratoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors