SOX2 Immunoexpression in High-Grade Gliomas: Potential Marker for Targeted Therapy
Gitika Aggarwal, Suash Sharma. Medical College of Georgia, Georgia Health Sciences University, Augusta, GA
Background: Gliomas may arise from neuroectodermal stem or progenitor cells. SOX (SRY-like HMG box) genes may be of particular interest as these represent a family of transcriptional cofactors implicated in the control of embryonic development of CNS. It is highly expressed within the embryonic neuroectodermal progenitors, and is downregulated as neural cells exit the cell cycle and differentiate. SOX genes are amplified/ upregulated in tumors, and Sox2 is overexpressed in malignant glioma. Sox2 silencing in glioblastoma tumor-initiating cells inhibits proliferation in mice. We aimed to study the distribution of Sox-2 positive cells in high-grade (malignant) gliomas.
Design: A total of 44 malignant gliomas (WHO grades 3 and 4) were identified from pathology archives. These were diagnosed and graded using WHO classification. These included 39 glioblastomas (GBM), 2 gliosarcomas (GS), 2 anaplastic astrocytomas (AA) and 1 anaplastic oligodendroglioma (AO). Sox2 immunohistochemistry was performed on formalin-fixed paraffin embedded tissue from these cases. The staining was reviewed for percentage positivity of tumor cells, staining intensity semiquantitatively (1+ to 4+), and various tumor patterns including positivity in infiltrating tumor cells (ITC), pseudopalisading, perivascular and pleomorphic tumor giant cells (PGC).
Results: All 44 (100%) malignant gliomas exhibited nuclear positivity of neoplastic cells. The control non-neoplastic autopsy brain tissues did not show any staining of normal cells or those in reactive gliosis. Of the tumors that showed specific patterns, 41/41 showed Sox2 positivity in ITC, 37/42 in perivascular tumor cell aggregates, 25/29 in pseudopalisading cells, and 5 had positivity in subpial accentuation. PGC were identified to be positive in 11/11 cases, including 1 GS. The sarcomatous component of GS was negative. Of note, endothelial cells in microvascular proliferation were negative. Only 11/44 (25%) showed <100% tumor cell staining varying from 5% to 90%, including 2 GS and 3 grade-3 gliomas.
Conclusions: The present study confirmed the strong immunoexpression of Sox2 in high grade gliomas, including all GBMs, and was undetectable in normal cortex. Since SOX2 immunoexpression in this study was also noted in infiltrating as well as perivascular and pseudopalisading (hypoxic) tumor cells, which are relatively refractory to chemoradiation, anti-Sox-2 targeted immunotherapy carries the potential to complement conventional therapy in high-grade gliomas.
Tuesday, March 20, 2012 2:30 PM
Platform Session: Section F, Tuesday Afternoon