p-CREB expression in human meningiomas: correlation with angiogenesis and recurrence risk.

Despite total surgical resection, a percentage of meningiomas do unexpectedly recur. At present the prediction of recurrence risk and the management of recurrent tumours represent major issues in the patients affected by meningiomas. The present study aims at investigating the prognostic value of the expression of the phosphorylated transcription factor cyclic AMP responsive element binding protein (p-CREB) in a series of meningiomas of different histotype and grade. While no p-CREB expression was found in specimens of normal leptomeninges, 71 % of meningiomas in our cohort expressed p-CREB. In addition, nuclear expression of p-CREB was present in the endothelia of tumor vessels in all of the meningiomas, but not in the vessels of the non-neoplastic meninges. High expression of p-CREB was significantly more frequent in meningiomas showing atypical, chordoid or microcystic histotype (P = 0.0003), high histological grade (P < 0.0001), high Ki-67 labeling index (P = 0.0001), high microvessel density counts (P < 0.0001) and high vascular endothelial growth factor expression (P = 0.0113). In addition, high p-CREB expression was significantly associated with the development of recurrences (P = 0.0031) and it was a significant negative, albeit not independent, prognostic factor for disease free survival in patients with meningiomas submitted to complete surgical removal (P = 0.0019). In conclusion, we showed that p-CREB is expressed in human meningiomas and that it represents a significant predictor of recurrence risk in these tumors. Due to its high expression in more aggressive tumors and in the tumor vessels, it may represent a novel therapeutic target in meningiomas.