Neuronal Markers Expression and Outcome in Glioblastoma
K Donev, BW Scheithauer, FJ Rodriguez, SM Jenkins. Mayo Clinic, Rochester, MN
Background: Recent studies have shown that high grade gliomas, particularly glioblastomas (GBM) featuring giant cells, often demonstrate immunoreactivity for neuronal markers. Such tumors were said to be associated with better outcome.
Design: Expression for synaptophysin, neurofilament protein, Neu-N,chromogranin and GFAP was analyzed in 82 cases, including 11 fibrillary, 8 gemistocytic, 40 giant cell and 23 small cell GBM. Median time to recurrence and death (separately) was estimated using Kaplan-Meier methods. Time to recurrence (or death) was compared in tumors between presence (GBMpos) or absence (GBMneg) of markers via Cox Proportional Hazards regression. The outcome (recurrence or death) was also compared between GBM expressing only one versus two or more neuronal markers. Giant cell and small cell categories were also individually analyzed. P-values less than 0.05 were considered statistically significant. All analyses were performed using SAS v. 8 (Cary, NC).
Results: Patient population included 48 males and 34 females with mean age of 54 at the time of diagnosis. Fourty five of 82 cases (54.8%) of GBM (5 fibrillary, 5 gemistocytic, 30 giant cell and 5 small cell) expressed at least one neuronal marker, synaptophysin being the most common (95%). At least one neuronal marker was expressed in 75% of giant cell, 62.5 % of gemistocytic, 45% of fibrillary and 21% of small cell GBM. There was no statistical significant difference in recurrence and survival time intervals between overall GBMpos and GBMneg as well as between GBMpos and GBMneg within giant cell and small cell categories. However, among those with positive markers, there was a significant difference in recurrence in the giant cell category between those with two or more markers versus a single marker (107 days vs. 265 days for two or more versus one marker, respectively, p = 0.02). Similarly, the risk of death was significantly higher for those with two or more markers as compared to those with a single marker (208 days vs. 258 days, p=0.03), and this difference looks to be driven by those within the giant cell category in particular (123 days vs. 295 days, p=0.026). This difference was not observed in small cell GBM category.
Conclusions: Neuronal markers expression is frequently present in various categories of GBM. Giant cell GBMs expressing 2 or more neuronal markers were associated with higher risk of recurrence and death as compared with giant cell GBM expressing a single neuronal marker.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 218, Monday Morning