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细胞粘附蛋白以及与血管生成和脂肪酸代谢相关的蛋白在良性、非典型性和间变性脑膜瘤中的表达

Expression of cell adhesion proteins and proteins related to angiogenesis and fatty acid metabolism in benign, atypical, and anaplastic meningiomas.

作者信息

Panagopoulos Alexandros Theodoros, Lancellotti Carmen Lucia Penteado, Veiga José Carlos Esteves, de Aguiar Paulo Henrique Pires, Colquhoun Alison

机构信息

Department of Neurosurgery, Santa Casa Hospital, São Paulo, Brazil.

出版信息

J Neurooncol. 2008 Aug;89(1):73-87. doi: 10.1007/s11060-008-9588-3. Epub 2008 Apr 17.

Abstract

Most meningiomas are benign tumours of arachnoidal origin, although a small number have high proliferative rates and invasive properties which complicate complete surgical resection and are associated with increased recurrence rates. Few prognostic indicators exist for meningiomas and further research is necessary to identify factors that influence tumour invasion, oedema and recurrence. Paraffin sections from 25 intracranial meningiomas were analysed for expression of the proteins vascular endothelial growth factor (VEGF), VEGF receptors Flt1 and Flk1, E-cadherin, metalloproteinases 2 and 9 (MMP2, MMP9), CD44, receptor for hyaluronic acid-mediated motility (RHAMM), hyaluronic acid (HA), CD45, cyclooxygenase 2 (COX2), brain fatty acid binding protein (BFABP), Ki67, and proliferating cell nuclear antigen (PCNA). Correlations among protein expression were found for several markers of proliferation (Ki67, PCNA, MI) and microvessel density (MVD). COX2 expression increased with increasing with tumour grade and correlated with Ki67, PCNA, MI, MVD, and BFABP. BFABP expression also correlated with Ki67 and PCNA expression. Relationships were also identified among angiogenic factors (VEGF, Flt1, Flk1) and proliferation markers. Oedema was found to correlate with MMP9 expression and MMP9 also correlated with proliferation markers. No correlations were found for MMP2, E-cadherin, or CD44 in meningiomas. In conclusion Ki67, PCNA, MI, MVD, BFABP, and COX2 were significantly correlated with meningioma tumour grade and with each other. These findings, by correlating both intracellular fatty acid transport and eicosanoid metabolism with tumour proliferation, as determined by Ki67 labelling and mitotic index, suggest fatty acids are involved in the progression of meningiomas.

摘要

大多数脑膜瘤是起源于蛛网膜的良性肿瘤,尽管少数脑膜瘤具有高增殖率和侵袭性,这使得完整的手术切除变得复杂,并与复发率增加相关。目前针对脑膜瘤的预后指标很少,有必要进一步研究以确定影响肿瘤侵袭、水肿和复发的因素。对25例颅内脑膜瘤的石蜡切片进行分析,检测血管内皮生长因子(VEGF)、VEGF受体Flt1和Flk1、E-钙黏蛋白、金属蛋白酶2和9(MMP2、MMP9)、CD44、透明质酸介导的运动受体(RHAMM)、透明质酸(HA)、CD45、环氧合酶2(COX2)、脑脂肪酸结合蛋白(BFABP)、Ki67和增殖细胞核抗原(PCNA)的蛋白表达。发现几种增殖标志物(Ki67、PCNA、MI)和微血管密度(MVD)之间存在蛋白表达相关性。COX2表达随肿瘤分级增加而升高,并与Ki67、PCNA、MI、MVD和BFABP相关。BFABP表达也与Ki67和PCNA表达相关。血管生成因子(VEGF、Flt1、Flk1)与增殖标志物之间也存在相关性。发现水肿与MMP9表达相关,MMP9也与增殖标志物相关。在脑膜瘤中未发现MMP2、E-钙黏蛋白或CD44之间存在相关性。总之,Ki67、PCNA、MI、MVD、BFABP和COX2与脑膜瘤肿瘤分级显著相关且相互之间也显著相关。这些发现通过将细胞内脂肪酸转运和类花生酸代谢与通过Ki67标记和有丝分裂指数确定的肿瘤增殖相关联,表明脂肪酸参与了脑膜瘤的进展。

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