Department of Human Pathology, University of Messina, Messina, Italy.
J Neurooncol. 2011 Apr;102(2):189-96. doi: 10.1007/s11060-010-0312-8. Epub 2010 Jul 21.
Despite total macroscopic resection of meningiomas relapses do occur in these tumours, possibly because of microscopic clusters of neoplastic cells left in the dura mater or in the arachnoid membrane. The invasiveness of the neoplastic cells of human meningiomas has been related to expression of matrix-metalloproteinase-9 (MMP-9), a peptidase actively implicated in the degradation of the extracellular matrix; nonetheless, the prognostic value of MMP-9 in the risk of recurrence of meningiomas has not been sufficiently investigated. Herein, we analysed MMP-9 expression in a series of meningiomas of different histotype and histological grade and assessed its correlation with various clinico-pathological indicators and with the clinical outcome of these tumours. We also tested the eventual pro-angiogenic role of MMP-9 expression in meningiomas through its correlation with vascular endothelial growth factor (VEGF) and microvessel density (MVD) revealed in the same cases. MMP-9 expression was observed in 64% of cases; high expression of this protein was significantly associated with high histological grade and proliferation index, but not with high MVD, of the tumours. A trend towards correlation between MMP-9 and VEGF expression was found, although statistical significance was not reached. In addition, high MMP-9 expression was a negative independent prognostic factor associated with higher recurrence risk in totally resected meningiomas. In conclusion, we demonstrated for the first time the potential prognostic value of MMP-9 expression in meningiomas. Inhibition of MMP-9 may be a new therapeutic strategy to prevent recurrences of meningiomas, particularly the high-grade type.
尽管脑膜瘤进行了全切除,但这些肿瘤仍会复发,这可能是因为硬脑膜或蛛网膜中残留有微小的肿瘤细胞簇。人类脑膜瘤的侵袭性与基质金属蛋白酶-9(MMP-9)的表达有关,MMP-9 是一种积极参与细胞外基质降解的肽酶;然而,MMP-9 在脑膜瘤复发风险中的预后价值尚未得到充分研究。在此,我们分析了不同组织类型和组织学分级的脑膜瘤中 MMP-9 的表达,并评估了其与各种临床病理指标的相关性,以及这些肿瘤的临床结果。我们还通过检测同一病例中血管内皮生长因子(VEGF)和微血管密度(MVD)的表达,测试了 MMP-9 表达在脑膜瘤中的潜在促血管生成作用。在 64%的病例中观察到 MMP-9 的表达;该蛋白的高表达与肿瘤的高组织学分级和增殖指数显著相关,但与高 MVD 无关。尽管未达到统计学意义,但发现 MMP-9 与 VEGF 表达之间存在相关性的趋势。此外,MMP-9 的高表达是一个独立的负预后因素,与完全切除的脑膜瘤的更高复发风险相关。总之,我们首次证明了 MMP-9 表达在脑膜瘤中的潜在预后价值。抑制 MMP-9 可能是预防脑膜瘤复发的一种新的治疗策略,尤其是高级别类型。