The hTERT protein as a marker for malignancy in meningiomas

The meningioma evolution remains problematic as 6 to 19% relapse after total resection. We have no criterion or marker to predict with certainty the tumour behaviour, and the WHO grading system is to a certain degree controversial. Telomerase expression seems to play an active role in conferring to the tumour cell indefinite life span. Telomerase activity has been documented via TRAP protocol and telomerase messenger expression (hTERT mRNA). In meningiomas the protein hTERT itself has not been studied directly. Thirty tumour samples of meningiomas operated in our Neurosurgical Department are reviewed with a mean follow-up of 4 years. Specifically hTERT protein, resection type, proliferation markers (Ki-67), and recurrences are evaluated. MRI is used for recurrence controls. Seven samples appeared to be hTERT-positive and all seven showed recurrence. Four patients had undergone a subtotal resection (STR). Among them two were hTERT-positive; only these showed recurrence and malignancy. Of the five macroscopically total resections (MTR), two were initially histologically benign and progressed to malignancy. A strong correlation was found between hTERT and recurrences (coefficient=0.989; p=0,01) with the Spearman's rho test, and weaker one between the Ki-67 and hTER (coefficient=0.672; p<0.0001). The hTERT staining revealed the presence of the hTERT protein not only in their nucleoli but sometime outside as nuclear speckles. The presence of nucleolar or subnuclear hTERT is directly correlated to recurrence and progression towards malignancy. Relocalisation of this protein was confirmed. A distinction is proposed between regrowth, based on normal proliferation (Ki-67) which can accompany subtotal resection and recurrence. Recurrence appears to be pathologic proliferation linked to hTERT presence. The hTERT presence predicts a sombre clinical outcome at mid-term for the individual patient.