Absence of IDH1 R132H Mutation Predicts Rapid Progression of Non-Enhancing Diffuse Glioma in Older Adults.
Adriana Olar, Aditya Raghunathan, Constance T Albarracin, Kenneth D Aldape, Daniel P Cahill, Suzanne Z Powell, Clay Goodman, Gregory N Fuller. Baylor College of Medicine, Houston, TX; University of Texas M.D. Anderson Cancer Center, Houston; The Methodist Hospital, Houston, TX
Background: Advanced age and the presence of contrast enhancement are regarded as poor prognostic factors in diffuse glioma. It is recognized that some diffuse gliomas can present initially as non-enhancing tumors and rapidly progress to a pattern of ring-enhancement, characteristic of glioblastoma (GBM) over a period of weeks to a few months. Mutations involving IDH1 (isocitrate dehydrogenase 1) have recently emerged as an important diagnostic, predictive and prognostic marker in glioma. R132H is the most common mutation, expressed in over 80% of WHO II and III diffuse gliomas and secondary GBM, but in less than 10% of primary GBM. In this study we correlate IDH1 R132H expression of non-enhancing gliomas in older adults with prognosis.
Design: Five patients with ages above 50 years and non-enhancing diffuse glioma were identified. Gliomas were classified according to the WHO 2007 grade, and 1p/19q deletion status when available. Representative sections were stained with an antibody specific for mutated IDH1 (anti-IDH1 R132H). Glioma outcome was correlated with IDH1 R132H status.
Results: Two groups of patients were identified. A favorable prognosis group included three patients, ages 51, 59 and 51 who presented with non-enhancing diffuse glioma, WHO grades III; II, 1p intact /19q deleted; and II, 1p/19q intact, respectively. All three tumors showed intense cytoplasmic and weaker nuclear IDH1 R132H staining. All three patients were alive and recurrence-free at the last contact with follow-up periods between 4 months and 3.8 years. A poor outcome group comprised two patients presenting with non-enhancing diffuse glioma WHO grades III and II at ages 51 and 55, respectively. The tumors rapidly progressed after 2 and 4 months, respectively, to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM, WHO IV. This group showed absent IDH1 R132H expression, which is characteristic of primary GBM.
Conclusions: Our study indicates that negative IDH1 R132H mutation status in non-enhancing diffuse glioma of older adults is a negative predictive factor associated with rapid progression to a higher grade, ring-enhancing GBM. The associated shorter interval of progression and negative IDH1 R132H mutation status suggests a similar de novo pathogenetic mechanism as in primary GBM.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 230, Tuesday Afternoon