Clinical significance of NF2 alteration in grade I meningiomas revisited; prognostic impact integrated with extent of resection, tumour location, and Ki-67 index

Abstract

NF2 alteration is the most commonly–found genetic abnormality in meningiomas and is known to initiate events for aggressive-type meningiomas. Whereas the prognosis of meningiomas differs depending on their epigenomic/transcriptomic profile, the effect of NF2 alteration on the prognosis of benign meningiomas is not fully elucidated. This study aimed to probe the importance of NF2 alteration in prognosis of WHO grade I meningiomas. A long-term retrospective follow-up (5.3 ± 4.5 years) study involving 281 consecutive WHO grade I meningioma patients was performed. We assessed tumour recurrence in correlation with extent of resection (EOR), histopathological findings, tumour location, and NF2 alteration. “NF2 meningioma” was defined as meningiomas with presence of NF2 mutation and/or 22q loss. Overall, NF2 meningioma per se was not a predictor of prognosis in the whole cohort; however, it was a predictor of recurrence in supratentorial meningiomas, together with EOR and Ki-67. In a striking contrast, NF2 meningioma showed a better prognosis than non-NF2 meningioma in infratentorial lesion. Supratentorial NF2 meningiomas had higher Ki-67 and forkhead box protein M1 expression than those of others, possibly explaining the worse prognosis in this subtype. The combination of NF2 alteration, high Ki-67 and supratentorial location defines subgroup with the worst prognosis among WHO grade I meningiomas. Clinical connotation of NF2 alteration in terms of prognosis of WHO grade I meningioma differs in an opposite way between supratentorial and infratentorial tumors. Integrated anatomical, histopathological, and genomic classifications will provide the best follow-up schedule and proactive measures.

Clinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas

“…6,33 One recent study found that among grade I NF2-mutated and non-NF2-mutated meningiomas that underwent STR, infratentorial tumors had significantly better PFS than supratentorial ones. 34 Indeed, we have demonstrated similar findings. Furthermore, among skull base meningiomas in general, decreased EOR does not seem to correlate with recurrence, 6 and the risk of recurrence plateaus approximately 8 years after surgery, unlike in non-skull base tumors in which the risk continues to increase with time.…”

Impact of Shape Irregularity in Medial Sphenoid Wing Meningiomas on Postoperative Cranial Nerve Functioning, Proliferation, and Progression-Free Survival

“…A meta-analysis investigating data from 677 patients revealed that TERT alterations predicted progression-free survival independent of the WHO grades in meningiomas [ 61 ]. Furthermore, loss of the NF2 suppressor gene at chromosome 22 has been demonstrated in a higher percentage (50–60%) of meningiomas, and supratentorial meningiomas with NF2 alterations had higher MIB-1 indices and a shorter time to tumor progression [ 62 , 63 ]. Those emerging molecular markers and their association with shape will be of importance in future studies.…”

Increased CD44 expression in primary meningioma: its clinical significance and association with peritumoral brain edema

“…Tumor location was categorized as supratentorial or infratentorial, as described previously. 17 All manipulations performed in the present study were in accordance with the 1964 Declaration of Helsinki and its later amendments. The study was approved by the local ethics committee at Hokkaido University Hospital.…”