[1679] Id4 Expression in Diffuse Gliomas: Is There a Correlation with Lineage and Grade?

R Kolhe, A Gonzalez, S Sharma. MCG, Augusta

Background: Id4 (inhibitor of differentiation), a member of helix-loop-helix (HLH) transcription factor family, dimerizes with basic HLH factors such as Olig1 and Olig2, to prevent transcriptional induction of downstream target genes. In neural progenitor cells, Id4 induction by BMP-4 treatment was noted to allow OLIG1/2 to co-localize with cytoplasmic Id4, thereby inhibiting oligodendroglial differentiation. Enforced expression of Id4 stimulates proliferation & blocks differentiation of oligodendrocyte precursor cells. Also, increased Id4 levels (mRNA/Protein) were detected in GBM & glioma cell lines. Therefore, we studied the immunoexpression of ID4 in diffuse gliomas (DG) of different lineages & grades.
Design: Immunostaining with antibody to ID4 was retrospectively examined on representative paraffin sections from 17 DG: these included 5 astrocytomas WHO grade-II (A), 5 anaplastic astrocytomas (AA), 3 glioblastomas (GBM), 1 glioblastoma-oligodendroglioma type (GBM-O), & 3 oligodendroglioma grade-II (OG). Percentage positivity of neoplastic cells for both nuclear & cytoplasmic staining was evaluated (<10% considered negative).
Results: Both nuclear & cytoplasmic immunoreactivity was noted. The percentage of positive cases is tabulated. Almost all DG (95%) showed nuclear immunoreactivity (except one recurrent post-radiation A) spread across all lineages and grades. In contrast, cytoplasmic ID4 expression was restricted to a proportion of high-grade astrocytic tumors, mainly gemistocytic/larger tumor cells. Oligodendroglial tumors, including GBM-O showed no significant cytoplasmic staining.

Id4 Stain Distribution in High-grade DG
Tumor TypeNuclear ID4 + casesMean % positive tumor cells (Range)Cytoplasmic ID4 + casesMean % positive tumor cells (Range)
AA (5)547 (25-80)3 (gemistocytic)42 (0-80)
GBM (3)368 (50-80)217 (0-25)
GBM-O (1)18500
T= 99 (100%)58 (25-85)5 (55%)29 (0-80)

Id4 Stain Distribution in Low-grade DG
Tumor TypeNuclear ID4 + casesMean % positive tumor cells (Range)Cytoplasmic ID4 + casesMean % positive tumor cells (Range)
A (5)438 (5-80)07 (1-9)
OG (3)337 (20-50)06 (1-9)
T= 87 (88%)38 (5-80)07 (1-9)

Conclusions: Nuclear ID4 expression was noted in 95% DG of all lineages & grades. The restricted immunoexpression of significant cytoplasmic Id4 only to a proportion of high-grade astrocytic tumors (in contrast to oligodendroglial tumors) suggests its selective role in transformation of astrocytic (especially gemistocytic) tumors, & may have prognostic value.
Category: Neuropathology

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 220, Monday Morning


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