Characterization of Switch/Sucrose Nonfermenting Complex Proteins and Nestin Expression in a Cohort of Pediatric Central Nervous System Tumors
Bibliographic record
Abstract
Tumors of the central nervous system (CNS) in pediatric patients have undergone significant diagnostic refinement through the use of immunohistochemistry (IHC) and molecular techniques. The utility of these novel IHC antibodies has been demonstrated with the inactivation of the switch/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in the diagnosis of atypical teratoid/rhabdoid tumors, predominantly through the loss of integrase interactor 1 (INI1; SMARCB1 ). Alternatively, these tumors may have inactivation of brahma-related gene 1 (BRG1; SMARCA4 ) in a subset of cases. The role of other SWI/SNF component proteins and their expression in pediatric brain tumors is not well established. Nestin, an intermediate filament, has been shown to be present in some pediatric CNS tumors, but of uncertain diagnostic and prognostic significance. We sought to explore the immunohistochemical expression profile for common SWI/SNF subunits and nestin in a pediatric CNS tumor cohort. Using a 118-sample tissue microarray, we performed IHC for INI1, BRG1, brahma (BRM), ARID1A, ARID1B, polybromo 1, and nestin. In 19 cases, INI1 was lost and BRG1 was lost in 2 cases. Interestingly, 6 cases originally diagnosed as primitive neuroectodermal tumors showed isolated loss of BRM. Other SWI/SNF proteins did not provide further diagnostic resolution. Nestin was positive in 76.2% of INI1/BRG1-deficient tumors, compared with 29.1% in INI1/BRG1-intact tumors yielding a sensitivity of 76.2%, specificity of 68.0%, and a P value of <0.001, but nestin positivity did not correlate specifically with poor outcomes. In conclusion, we confirm the utility of BRG1 IHC in the workup of pediatric CNS tumors, which may facilitate a difficult diagnosis when conventional markers are inconclusive, or as a first-line marker in cases where intraoperative smears are suggestive of atypical teratoid/rhabdoid tumor. Although nestin expression was associated with SWI/SNF inactivation, it did not yield statistically significant diagnostic or prognostic information in our study. Interestingly, we identified 6 tumors with isolated BRM IHC loss, the significance of which is uncertain but warrants further investigation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".