Expression of c-Met in invasive meningioma

Abstract

Introduction: Meningiomas are divided into three grades according to 2007 WHO classification and most meningiomas are benign (WHO grade I). However, meningiomas show high recurrence rate even after curative tumor removal and invasiveness of tumor may contribute to the high recurrence rate. Recently, c-Met, HGF, AQP1 and NKCC1 have been reported to be involved in cancer invasion. The aim of this study was to elucidate whether protein expressions of c-Met, HGF, AQP1 and NKCC1 were associated with clinicopathologic variables as well as brain and bone/scalp invasion in large scale of meningiomas. Methods: We examined immunohistochemical expression of c-Met, HGF, AQP1 and NKCC1 in 198 cases of meningiomas treated with curative tumor removal (Simpson grade I or II). Kaplan – Meier analyses were used to evaluate whether patients with meningioma had a different recurrence free survival depending on c-Met, HGF, AQP1 and NKCC1 expression status. Results: c-Met-High was observed in 18.9% (35/185) without brain invasion and 46.2% (6/13) meningiomas with brain invasion. c-Met-High significantly correlated with brain invasion. (P = 0.030) And it was also observed in 18.4% (32/174) of meningiomas without bone/scalp invasion and in 37.5% (9/24) of meningiomas with bone/scalp invasion. There was a tendency for increased c-Met-High in meningiomas with bone/scalp invasion compared with meningiomas without bone/scalp invasion, although statistical significance was not reached. (P = 0.055) HGF-High did not show statistical association with brain invasion or bone/scalp invasion. (P = 0.222, P = 0.108, respectively) On the other hand, AQP1-High showed significant inverse correlation with brain invasion. (31.9% [59/187] vs. 0% [0/11], P = 0.011) But AQP1-High showed no significant difference in bone/scalp invasion. (P = 0.812) NKCC1 did not show statistical association with brain invasion or bone/scalp invasion. (P = 0.598, P > 0.9, respectively) c-MET-high showed shorter recurrence free survival (93.467 ± 8.211 months) than c-MET-low (96.131 ± 1.911 months) however, it did not reach statistical significance. (P = 0.139) There was no association of HGF-high, AQP1-High and NKCC1-High expression with recurrence free survival. Conclusions: We demonstrated that c-Met-High was associated with brain invasion of meningiomas and that c-Met expression could be a useful predictive marker for meningioma recurrence.