Loss of INI1 protein expression defines a subgroup of aggressive central nervous system primitive neuroectodermal tumors.
Pediatric embryonal brain tumors can be difficult to classify. Atypical teratoid rhabdoid tumors (ATRT) contain rhabdoid cells, while primitive neuroectodermal tumors (PNETs) are composed of "small round blue cells." Loss of INI1 is a common event in ATRT; therefore, we investigated if the loss of INI1 protein expression was also observed in central nervous system (CNS) PNET and pineoblastoma. A histological review of 42 CNS PNETs and six pineoblastomas was performed. INI1 expression was assessed by immunohistochemistry. Sequencing was performed on the mutational hotspots of INI1. INI1-immunonegative tumors were further investigated using fluorescence in situ hybridization. Epithelial membrane antigen (EMA) protein expression was assessed in six CNS PNETs to further define the phenotype. Five CNS PNETs without rhabdoid cell morphology were immuno-negative for both INI1 and EMA. Of these primary CNS PNET patients, three died <11 months postdiagnosis, which was dissimilar to the INI1-immunopositive primary CNS PNETs where 18/24 (75%) patients were alive 1 year postdiagnosis. We have identified a small subgroup of CNS PNETs which lack INI1 protein expression, but have no evidence of rhabdoid cell morphology. INI1 protein loss may occur through mechanisms other than gene deletion. INI1 immunohistochemistry should be performed for all CNS PNET cases.
Children's Brain Tumour Research Centre, School of Clinical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Suzanne
S
Miller
Jennifer H
JH
Ward
Hazel A
HA
Rogers
James
J
Lowe
Richard G
RG
Grundy
D000293:Adolescent; D001932:Brain Neoplasms / Q000145:classification / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018396:Mucin-1 / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D018242:Neuroectodermal Tumors, Primitive / Q000145:classification / Q000378:metabolism*; D010870:Pineal Gland / Q000473:pathology; D010871:Pinealoma / Q000378:metabolism; D040081:Protein Array Analysis; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D018396:Mucin-1; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors