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磁共振灌注加权成像根据1p19q和表皮生长因子受体(EGFR)状态定义少突胶质细胞瘤的血管生成亚型。

Magnetic resonance perfusion-weighted imaging defines angiogenic subtypes of oligodendroglioma according to 1p19q and EGFR status.

作者信息

Kapoor Gurpreet S, Gocke Timothy A, Chawla Sanjeev, Whitmore Robert G, Nabavizadeh Ali, Krejza Jaroslaw, Lopinto Joanna, Plaum Justin, Maloney-Wilensky Eileen, Poptani Harish, Melhem Elias R, Judy Kevin D, O'Rourke Donald M

机构信息

Department of Neurosurgery, University of Pennsylvania, 3 Silverstein 3400 Spruce Street, Philadelphia, PA 19104, USA.

出版信息

J Neurooncol. 2009 May;92(3):373-86. doi: 10.1007/s11060-009-9880-x. Epub 2009 Apr 9.

Abstract

1p19q LOH has been shown to predict radio- and chemosensitivity and prolonged survival in oligodendrogliomas (OLs). We have recently shown that magnetic resonance perfusion-weighted imaging (MR-PWI) may be useful in predicting the histopathological grade or cytogenetic type of oligodendroglial neoplasms. MR-PWI allows noninvasive determination of relative tumor blood volume (rTBV), which may reflect the degree of neoplastic angiogenesis and metabolism. The present study was aimed to correlate rTBV to the angiogenic markers and EGFR expression in oligodendroglial tumors with 1p/19q LOH or 1p LOH (Group 1) and 1p19q intact alleles or 19q LOH (Group 2), respectively. In WHO grade II neoplasms, Group 1 showed significantly greater rTBV than Group 2 (P = 0.013). However, the differences between Group 1 and Group 2 were not significant in grade III tumors. Probe-based real-time RT-PCR analyses showed that 12% of Group 2 high-grade tumors with intact 1p19q exhibited dramatic EGFR overexpression (designated EGFR-high). Grade III neoplasms showed a significantly higher rTBV than grade II neoplasms. Group 1 tumors showed significantly higher rTBV than Group 2 tumors, independent of the EGFR-high subtype. Real-time RT-PCR analyses showed increased expression of VEGF, CD31 and CD105 in Group 1 tumors as compared to Group 2 tumors, excluding the EGFR-high subtype. Multivariable linear regression analysis showed a significant association of rTBV with 1p19q LOH, and expression of EGFR and VEGF. Therefore, the combined use of extensive molecular profiling and advanced MR imaging modalities may improve the accuracy of tumor grading, provide prognostic information, and has the potential to influence treatment decisions.

摘要

1p19q杂合性缺失已被证明可预测少突胶质细胞瘤(OLs)的放射敏感性和化学敏感性以及生存期延长。我们最近表明,磁共振灌注加权成像(MR-PWI)可能有助于预测少突胶质细胞瘤的组织病理学分级或细胞遗传学类型。MR-PWI可无创测定相对肿瘤血容量(rTBV),其可能反映肿瘤血管生成和代谢程度。本研究旨在分别将rTBV与1p/19q杂合性缺失或1p杂合性缺失(第1组)以及1p19q完整等位基因或19q杂合性缺失(第2组)的少突胶质细胞瘤中的血管生成标志物和表皮生长因子受体(EGFR)表达进行关联分析。在世界卫生组织(WHO)II级肿瘤中,第1组的rTBV显著高于第2组(P = 0.013)。然而,在III级肿瘤中,第1组和第2组之间的差异不显著。基于探针的实时逆转录聚合酶链反应(RT-PCR)分析显示,1p19q完整的第2组高级别肿瘤中有12%表现出显著的EGFR过表达(称为EGFR高表达)。III级肿瘤的rTBV显著高于II级肿瘤。第1组肿瘤的rTBV显著高于第2组肿瘤,与EGFR高表达亚型无关。实时RT-PCR分析显示,与第2组肿瘤相比,第1组肿瘤中血管内皮生长因子(VEGF)、CD31和CD105的表达增加,但不包括EGFR高表达亚型。多变量线性回归分析显示rTBV与1p19q杂合性缺失、EGFR和VEGF的表达显著相关。因此,广泛的分子谱分析和先进的磁共振成像模式的联合应用可能会提高肿瘤分级的准确性,提供预后信息,并有可能影响治疗决策。

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