Utility of Olig2 and Notch-1 Immunostains in Glioblastomas in a Routine Histopathology Setting
Olivia L Snir, Amy F Ziober, Michael D Feldman, Zissimos Mourelatos. University of Pennsylvania, Philadelphia, PA
Background: High-grade gliomas are nearly uniformly fatal and have a dismal prognosis. Recent studies have identified subclasses of high-grade gliomas by molecular arrays. One subclass, referred to as the Proneural phenotype, carries prognostic and therapeutic significance. This phenotype correlates with longer survival and may predict response to Notch inhibitors. To date, only gene expression profiling is able to reliably subclassify glioblastomas (GBMs); development of simple assays that can be adopted to a routine histopathology setting are thus desirable. In this study, we test two immunohistochemical stains for their utility in glioblastomas in a clinical laboratory setting.
Design: Forty cases of newly diagnosed resected glioblastomas from 2005 at the Hospital of the University of Pennsylvania are included in this study. To test these cases, antibodies to Olig2 and Notch-1 are initially considered. The staining pattern is scored semi-quantitatively as minimal (0), mild (1), mild/moderate (1.5), moderate (2), or strong (3) for both of these immunostains. Only nuclear staining is considered. Cases that are predominately positive for Olig2 and Notch-1 are expected to belong to the Proneural subclass. As such, cases with increased Olig2 and Notch-1 staining are assigned a Proneural phenotype. Kaplan-Meier analysis is performed to study survival of this subclass. Additionally, overall survival as a function of strength of staining is analyzed for each immunostain.
Results: Cases of glioblastomas demonstrated variable staining with both Olig2 and Notch-1 immunostains. There was a trend towards longer median survival with stronger Olig2 staining and stronger Notch-1 staining; however, these trends did not reach statistical significance. Cases with strong Olig2 staining had a median survival of 73.6 weeks vs 47.3 weeks. Cases with only minimal or mild Notch-1 staining had a median survival of 24.4 weeks vs 56.4 weeks. The overall median survival was 48.3 weeks.
Conclusions: 1. Stains to Olig2 and Notch-1 may be adopted in a clinical setting to test glioblastomas by IHC.
2. Increased Olig2 and Notch-1 staining trended towards improved survival of glioblastomas in this study. However, immunohistochemistry with these markers alone is not able to reliably subclassify GBMs.
3. Further studies should be considered to subclassify GBMs with additional IHC markers and to relate Notch-1 staining patterns to response to Notch inhibitors.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 242, Wednesday Afternoon