endothelin-1 and Meningioma

Several hypotheses have been proposed regarding the mechanisms underlying meningioma-related hyperostosis. In this study, we investigated the role of osteoprotegerin (OPG), insulin-like growth factor 1 (IGF-1), endothelin 1 (ET-1), and bone morphogenetic protein (BMP) 2 and 4.. A total of 149 patients (39 males and 110 females; mean age, 62 years) who underwent surgery were included. Depending on the relationship with the bone, meningiomas were classified as hyperostotic, osteolytic, infiltrative, or unrelated. Expression of OPG, and IGF-1, ET-1, BMP-2, and BMP-4 was evaluated by tissue microarray analysis of surgical samples.. Our series comprised 132 cases of grade I, 14 cases of grade II, and 3 cases of grade III meningiomas, according to the World Health Organization classification. Based on preoperative computed tomography scan, the cases were classified as follows: hyperostotic, n = 11; osteolytic, n = 11; infiltrative, n = 15; unrelated to the bone, n = 108. Four cases were excluded from the statistical analysis. Using receiver operating characteristic curve analysis, we identified a 2% cutoff for the mean value of IGF-1 that discriminated between osteolytic and osteoblastic lesions; cases with a mean IGF-1 expression of <2% were classified as osteolytic (P = 0.0046), whereas those with a mean OPG expression of <10% were classified as osteolytic (P = 0.048). No other significant relationships were found.. Expression of OPG and expression of IGF-1 were found to be associated with the development of hyperostosis. Preliminary findings suggest that hyperostosis can be caused by an overexpression of osteogenic molecules that influence osteoblast/osteoclast activity. Based on our results, further studies on hyperostotic bony tissue in meningiomas are needed to better understand how meningiomas influence bone overproduction.

Topics: Biomarkers; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Endothelin-1; Female; Gene Expression; Humans; Hyperostosis; Insulin-Like Growth Factor I; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Osteoprotegerin

Neoangiogenesis has been correlated to biological aggressiveness and an adverse clinical course of several neoplasias. Its prognostic role in meningiomas appears to be controversial. Nonetheless, if adequately quantified with specific markers and appropriate scoring methods, angiogenesis seems to be significantly associated with a high growth fraction, development of recurrences and shorter overall survival of meningiomas. As a consequence, neoangiogenesis may represent a target for therapies aimed at reducing the growth of inoperable meningiomas or recurrence risk of totally resected tumors. Even more significantly, the identification of the factors that mediate angiogenesis in meningiomas could help us to determine appropriate novel anti-angiogenic therapies for these tumors. Herein the methods for quantification of angiogenesis as well as its regulating factors in meningiomas are reviewed.

Topics: Antigens, CD; Biomarkers, Tumor; Caveolin 1; Endoglin; Endothelin-1; Humans; Immunohistochemistry; Matrix Metalloproteinase 9; Meningioma; Neovascularization, Pathologic; Neuropilin-1; Prognosis; Receptors, Cell Surface; Semaphorin-3A; Somatostatin; Vascular Endothelial Growth Factor A

Meningiomas are one of the most frequent central nervous system tumours. Although slow-growing at times, they continue to be a cause of morbidity and mortality. The endothelin (ET) family consists of three isoforms: ET-1 is the most abundant one. ET-1 may be involved in meningioma tumourigenesis in concert with other growth factors, in particular with angiogenic agents. We analysed ET-1 expression by immunohistochemistry and its activating system by reverse-transcription-polymerase chain reaction in 56 cases of meningioma. We found an association between high-grade meningiomas and high ET-1 expression levels (p=0.002). Moreover, we evaluated the potential angiogenic role of ET-1, finding an elevated microvessel count in tumours with high ET expression levels (p=0.004). ET-1 may contribute to meningioma growth by inducing formation of new blood vessels. The finding that ET-1 expression positively correlates with vascular endothelial growth factor (VEGF) expression in meningiomas (p=0.03) also supports the hypothesized modulating effect of ET-1 on angiogenesis. Thus, the influence of the ET system on the progression of meningiomas may occur through stimulation of VEGF. The association of ET-1 and meningioma represents a potential area for therapeutic intervention with selective ET inhibitors. Additional clinical studies will be needed before inhibitors can be incorporated in clinical practice.

Topics: Adult; Aged; Endothelin-1; Female; Humans; Immunohistochemistry; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neovascularization, Physiologic; RNA, Messenger; Vascular Endothelial Growth Factor A