Article
Distinct chromosomal and microsatellite instability profiles in giant-cell glioblastoma multiforme compared to standard glioblastoma
Unterschiedliches molekulargenetisches Profil von Riesenzell-GBMs im Vergleich zu Standard-GBMs
Search Medline for
Authors
Published: | April 23, 2004 |
---|
Outline
Text
Objective
Giant cell glioblastoma (gcGBM) is a peculiar variant of glioblastoma multiforme (GBM) characterized by a preponderance of multinucleated giant cells. Compared to ordinary glioblastoma it shows a distinct clinicopathological and molecular profile. The mechanisms implicated in genomic instability have not been yet described in gcGBM.
Methods
We analyzed the mutational spectrum of p53 and PTEN, analyzed EGFR amplification as well as microsatellite instability (MSI) and mismatch repair (MMR) protein expression in 14 gcGBM in order to assess genomic instability and compared it with 52 standard GBMs. Student´s t-test was performed to investigate immunohistochemical protein densitometry. Two-tailed Fisher´s exact test was used to analyze the significance of p53, EGFR and PTEN. Odds ratios and 95% confidence intervals were obtained through logistic regression.
Results
Multiple p53 mutations affecting single specimens were frequently observed (11 out of 14 samples, 78.6%, P<0.05), including a remarkably high rate of acceptor site splice mutations in 6 gcGBMs compared to standard glioblastomas (P<0.05). Low-level MSI was more frequent in gcGBM compared to common GBMs (28.6% vs. 8.5%, P<0.05). A deficient expression of the MMR proteins MLH1 and PMS2 was observed in the giant-cell phenotype of two MSI(+) tumors. PTEN was mutated in all gcGBM except in those showing MSI.
Conclusions
These results strongly suggest that gcGBM differs from ordinary GBM in the rate and pattern of both chromosomal and microsatellite instability, which might contribute to explain the distinct clinicopathological features of these tumors.