Expression of c-MET in Invasive Meningioma

Meningioma is a common intracranial tumor arising from the meningothelial (arachnoid) cells. Meningiomas are divided into 15 histologic subtypes and three grades, including benign (grade I), atypical (grade II), and anaplastic (grade III) [1]. Most meningiomas are benign, corresponding to World Health Organization (WHO) grade I, and they have a favorable outcome. Alternatively, grade II atypical meningiomas and grade III anaplastic meningiomas have less favorable outcomes [2,3]. Even in benign cases, meningiomas have high recurrence rates after curative surgical treatment. They have been estimated to recur in 7%–25%, 29%–52%, and 50%–94% of cases in grades I, II, and III, respectively [4]. Several markers, such as the proliferation index, the vascular density marker, and the expression of sex hormone receptors, are suggested for predicting the recurrence rates of tumors. However, it is generally accepted that both histopathological features, including histologic subtypes and clinical data, have limitations in their use as reliable markers for predicting tumor recurrence due to low accuracy [5-8]. Previous studies report an association among meningiomas, brain or bone invasion, and higher tumor recurrence rates. However, the mechanism of invasion has not been well established [9-12]. Also called a hepatocyte growth factor (HGF), c-MET is a receptor tyrosine kinase that, upon binding of its ligand, is phosphorylated. Subsequently, c-MET activates the signaling pathway of cell proliferation and migration. The c-MET/HGF signaling pathway was first described as an oncogene in the 1980s. Accordingly, it has been known to induce tumor cell proliferation, motility, and invasion, as well as to promote angiogenesis in several human cancers, such as breast, lung and hepatocellular carcinomas [13-16]. In meningiomas, the expression of c-MET/HGF has been reported to have a diverse relationship with tumor recurrence, angiogenesis, histologic subtypes, and the invasiveness of the meningioma. Existing reports are based on a limited number of samples and different methods, such as enzymelinked immunosorbent assay, immunohistochemistry or reverse transcription polymerase chain reaction (RT-PCR) [17-19]. To date, little is known about their expression in invasive meningiomas. The aim of this study, therefore, is to elucidate whether the protein expressions of c-MET and HGF are associated with clinicopathologic variables, as well as brain and bone/soft tissue invasion of meningiomas, in large scale studies of meningioma.