A role for chromosome 9p21 deletions in the malignant progression of meningiomas and the prognosis of anaplastic meningiomas.
Meningiomas display significant variability in terms of recurrence and survival rates, even within tumor grade. Although several recent modifications of the grading system have improved our ability to predict biologic behavior, additional prognostic markers are needed. Inactivation of the cell cycle regulator, p16 (CDKN2A), has recently been observed in a small subset of atypical and the majority of anaplastic meningiomas. To assess the potential clinical utility of this marker, we performed dual-color FISH on 117 well-characterized archival meningiomas using paired commercial probes to the chromosome 9 centromeric (CEP9) and p16 (9p21) regions. Benign meningiomas (N = 42) were divided into non-recurring versus recurring groups. Atypical meningiomas (N = 52) consisted of proliferative and brain invasive subsets. The 23 anaplastic meningiomas were not further stratified. Deletion of p16 or monosomy 9 was seen in 17% of benign, 52% of atypical, and 74% of anaplastic meningiomas (p < 0.001). No statistically significant differences were found among subsets of benign or subsets of atypical meningioma, though there were more recurrences in those with deletion. Despite potential effects on cell cycle regulation, p16 deletions were not restricted to meningiomas with a high proliferative index. Most importantly, p16 deletion was strongly associated with survival in the anaplastic meningioma cohort, with a risk ratio for death of 6.79 (p = 0.016). Conversely, absence of deletion identified a subset of anaplastic meningioma patients (26%) with prolonged survival. We conclude that chromosome 9p21 deletions are associated with malignant progression of meningiomas and poor prognosis in anaplastic meningiomas.
Perry
Arie
A
Division of Neuropathology, Washington University School of Medicine, St. Louis, Mo 63110-1093, USA. aperry@pathbox.wustl.edu
Banerjee
Ruma
R
Lohse
Christine M
CM
Kleinschmidt-DeMasters
Bette K
BK
Scheithauer
Bernd W
BW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D008579:Meningioma / Q000235:genetics* / Q000503:physiopathology*; D008875:Middle Aged; D011379:Prognosis