Fluorescent in situ hybridization and ex vivo 1H magnetic resonance spectroscopic examinations of meningioma tumor tissue: is it possible to identify a clinically-aggressive subset of benign meningiomas?
OBJECTIVE
Although histologically benign, Grade I meningiomas can sometimes behave aggressively. The clinically-aggressive subset of Grade I meningiomas is typically indistinguishable from clinically-benign Grade I meningiomas in vivo. We compared molecular genetic and biochemical findings to clinical, pathological, and immunohistochemical information in a series of clinically-aggressive Grade I meningiomas with a series of clinically-benign meningiomas to identify characteristics that may be used to distinguish between these two groups.


METHODS
Tumor tissue samples from 30 patients with Grade I meningiomas were harvested. Half of the sample was embedded in paraffin to be used for fluorescent in situ hybridization to examine aberrations of chromosomes 1p, 14q, and 22q; the other half was snap frozen and examined with proton magnetic resonance spectroscopy to identify concentrations of key metabolites in the tissue ex vivo. Clinical and pathological parameters were retrospectively reviewed as part of routine clinical management. These data were evaluated for potential unique associations with diagnostic significance.


RESULTS
Molecular genetic and biochemical findings correlated with clinical behavior of the two Grade I meningioma groups. Specific chromosomal abnormalities correlated with the aggressive phenotype: homogeneous loss of 1p, homogeneous loss of 14q, and the presence of any of the examined chromosomal aberrations (P < 0.05). The presence of aberrations also influenced meningioma regrowth after subtotal resection. The ratio of choline to glutamate correlated with histopathological subtype (P < 0.05). The ratio of glutamine to glutamate, and the ratio of glycine to total glutamine and glutamate, and creatine correlated with recurrence. Alanine was decreased in meningiomas with chromosomal aberrations in tumors that recurred.


CONCLUSIONS
Distinct molecular genetic and biochemical alterations differentiated clinically-aggressive Grade I meningiomas from clinically-benign Grade I meningiomas.
Pfisterer
Wolfgang K
WK
Neurosurgery and Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
Hendricks
William P
WP
Scheck
Adrienne C
AC
Nieman
Ronald A
RA
Birkner
Thomas H
TH
Krampla
Wolfgang W
WW
Preul
Mark C
MC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008579:Meningioma / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011522:Protons; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011522:Protons