c-Myc Protein Expression Is Prognostic of Survival in Embryonal Brain Tumor Patients
DAR Kanagasabapathy, Y Morales-Odia, CG Eberhart. Johns Hopkins University, Baltimore, MD
Background: Medulloblastoma and other embryonal neoplasms represent the most common childhood brain tumors. Despite significant advances in their treatment, a high proportion of surviving patients suffer from long-term debilitating neurologic side effects. This is in part due to a lack of reliable prognostic markers in routine histopathologic examination which might allow lesser doses of craniospinal irradiation to be given to patients whose tumors have a less aggressive profile. c-myc mRNA levels and gene dosage have been shown previously to be associated with anaplasia and poor patient outcomes in medulloblastoma, however, c-myc protein expression has not been examined. The goal of our study is therefore to evaluate c-Myc protein as a potential prognostic marker using formalin-fixed, paraffin embedded samples.
Design: We studied c-myc expression in 80 patients whose embryonal tumors were included on a tissue microarray. Immunohistochemistry was performed with a newly developed rabbit monoclonal antibody from Epitomics (Burlingame, CA, Clone Y69) using standard techniques. Cores were scored in a semi-quantitative fashion (0 to 3+) for nuclear expression of antigen. At least two intact cores were required for a case to be included in the analysis.
Results: The 65 cases that could be evaluated included 54 cases of medulloblastoma, 8 cases of supratentorial primitive neuroectodermal tumor (sPNET) and 3 atyptical teratoid/rhabdoid tumors. Of these 23% (15/65) showed nuclear immunopositivity for c-Myc while the remainder (77%) were negative. Five cases were 2+ positive, three cases showed 3+ positivity and the remainder was 1+ in staining intensity. c-Myc positive cases were present in all categories and cytoplasmic immunoreactivity was limited to only a few tumors. Cases stratified on the basis of expression of c-Myc protein (positive vs negative) showed a significant difference in survival rates by logrank analysis of Kaplan-Meier curves (p=0.03).
Conclusions: Our data suggest that c-Myc protein immunoreactivity may represent a novel predictor of shorter survival in patients with embryonal brain tumors.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 239, Tuesday Afternoon