Gliomas Arising in Patients with Multiple Sclerosis Have No Distinctive Genetic Features
Hilary S Serracino, Adam Khalil, Denise Damek, Douglas Ney, Kevin O Lillehei, Bette K Kleinschmidt-DeMasters. University of Colorado at Denver, Aurora, CO
Background: The co-occurrence of gliomas and multiple sclerosis (MS) in the same patient is uncommon, but a well-reported phenomenon, with 39 cases in the literature since 1980. One-third of these gliomas have been glioblastomas (GBMs), although oligodendrogliomas and astrocytomas, WHO grade II and III, have also been reported. In most cases, the glioma has developed many years after the diagnosis of MS, leading authors to postulate that chronic inflammation and chronic gliosis in demyelinative plaques is the underlying substrate for secondary induction of a glial neoplasm. Until recently, however, additional molecular or genetic tools have not been available to test the hypothesis as to whether high-grade gliomas might arise from chronic gliosis, with transformation to low grade glioma, and eventually GBM, i.e., be secondary GBMs.
Design: We utilized text word searches of our databases to identify MS-gliomas and assessed for the first time all MS-GBMs for immunohistochemical (IHC) and genetic markers more frequently associated with secondary than primary GBMs, namely IDH-1 and p53 IHC, as well as for LOH 10q (PTEN locus) and EGFR amplification, two features more characteristic of primary than secondary GBM. The eight cases identified (5 males: 3 females) represent the second largest series of MS-gliomas in the literature and include a tumor type not previously reported, an incidental pilocytic astrocytoma of midbrain identified at autopsy. This represented the only autopsy case in >175 MS brains in our Rocky Mountain MS Tissue Bank. The mean and median age at glioma diagnosis for our cases was 45.4 and 49 years for men, and 49 and 41 years for women, respectively. These numbers are comparable to mean and median age at glioma diagnosis previously reported in the literature: 49.06 and 47.5 years for men and 45.38 and 44.5 years for women, respectively.
Results: None of the 4/8 GBMs showed IDH-1 + IHC and no distinctive pattern was detectable for PTEN loss or EGFR amplification. Only 1/4 GBMs had nuclear p53 IHC in greater than 90% of the cells.
Conclusions: Our genetic data, when taken together with epidemiological data from our MS Brain Bank, shows no strong prevalence of gliomas in MS patients and further argues against the hypothesis that gliosis in MS predisposes to glioma formation, i.e., secondary GBMs.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 279, Tuesday Afternoon