S100B

Overview

S100B is a calcium-binding protein validated as an IHC protein marker for the MG1 molecular group of meningiomas in an integrative molecular classification study.

Alterations observed in the corpus

  • S100B protein expression was validated by IHC as a discriminative marker for the MG1 (low-risk, NF2-mutant) molecular group of meningiomas in a 121-patient discovery cohort; the four-marker IHC panel (S100B, SCGN, ACADL, MCM2) enables molecular group assignment in conventional neuropathology laboratories PMID:34433969.
  • S100B is a canonical Schwann cell precursor (SCP) marker absent from the novel hC1 progenitor cluster in postnatal human adrenal gland; hC1 cells lack S100B expression (alongside SOX10 and FOXD3), distinguishing them from classical SCPs (FDR <0.01, Welch’s t-test on 1,322 nuclei). PMID:34493726

Cancer types (linked)

  • MNG — IHC marker for MG1 molecular group; the four integrative molecular groups outperform WHO grading for predicting recurrence PMID:34433969.
  • NBL — used as a negative marker for SCP identity in postnatal human adrenal gland; absent in the novel NTRK2+/CLDN11+ cholinergic progenitor cluster hC1 proposed as the cell-of-origin for high-risk neuroblastoma. PMID:34493726

Co-occurrence and mutual exclusivity

  • S100B marks MG1, which is near-universally NF2-mutant (88%) and low-risk; molecularly distinct from MG2 (TRAF7/AKT1/KLF4/SMO-driven) and MG3/MG4 (chromatin remodeling-driven) groups PMID:34433969.
  • Mutually exclusive with NTRK2 and CLDN11 co-expression in postnatal adrenal gland; absence of S100B (with SOX10 and FOXD3) defines the non-SCP identity of the hC1 progenitor. PMID:34493726

Therapeutic relevance

  • No direct targeted therapy. Proteomic marker utility enables routine molecular grouping which may inform future WHO classification revisions and trial stratification PMID:34433969.

Open questions

  • Independent validation of the four-marker IHC panel in larger prospective meningioma cohorts is required PMID:34433969.

Sources

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