Related Experiment Video
Updated: May 21, 2026
Identifying, Diagnosing, and Grading Malignant Peripheral Nerve Sheath Tumors in Genetically Engineered Mouse Models
Published on: May 17, 2024
Loss of INI1 protein expression defines a subgroup of aggressive central nervous system primitive neuroectodermal
Suzanne Miller1, Jennifer H Ward, Hazel A Rogers
1Children's Brain Tumour Research Centre, School of Clinical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Abstract:
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.
Insights
Loss of INI1 protein expression was identified in a subset of pediatric central nervous system (CNS) primitive neuroectodermal tumors (PNETs) lacking rhabdoid cells. This finding suggests INI1 immunohistochemistry is crucial for classifying CNS PNETs.
Area of Science:
- Neuro-oncology
- Pediatric Pathology
- Molecular Diagnostics
Background:
- Pediatric embryonal brain tumors, including atypical teratoid rhabdoid tumors (ATRT) and primitive neuroectodermal tumors (PNETs), present classification challenges.
- Atypical teratoid rhabdoid tumors are characterized by rhabdoid cells and frequent INI1 protein loss.
- Primitive neuroectodermal tumors are defined by small round blue cells, but their relationship with INI1 expression requires further investigation.
Purpose of the Study:
- To investigate the prevalence and implications of INI1 protein loss in central nervous system (CNS) PNETs and pineoblastomas.
- To determine if INI1 protein loss occurs in CNS PNETs lacking rhabdoid cell morphology.
- To assess the prognostic significance of INI1 expression in CNS PNETs.
Main Methods:
- Histological review of 42 CNS PNETs and six pineoblastomas.
- Immunohistochemistry to assess INI1 and epithelial membrane antigen (EMA) protein expression.
- Sequencing of INI1 mutational hotspots and fluorescence in situ hybridization (FISH) for INI1-immunonegative cases.
Main Results:
- A subgroup of five CNS PNETs without rhabdoid morphology showed loss of both INI1 and EMA protein expression.
- Patients with INI1-immunonegative CNS PNETs had a poorer prognosis, with three deaths within 11 months.
- In contrast, 75% of INI1-immunopositive CNS PNET patients survived at least 1 year postdiagnosis.
Conclusions:
- Identified a distinct subgroup of CNS PNETs characterized by INI1 protein loss but absence of rhabdoid cells.
- INI1 protein loss in this subgroup may result from mechanisms other than gene deletion.
- INI1 immunohistochemistry is recommended for all CNS PNET diagnoses to aid classification and prognostication.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:15Insensitive Nuclei Enhanced by Polarization Transfer (INEPT)
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...