Jenkinson Michael D, Smith Trevor S, Joyce Kathy A, Fildes Diane, Broome John, du Plessis Daniel G, Haylock Brian, Husband David J, Warnke Peter C, Walker Carol
Department of Neurosurgery, The Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
Neuroradiology. 2006 Oct;48(10):703-13. doi: 10.1007/s00234-006-0122-z. Epub 2006 Aug 26.
The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the -1p/-19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy.
Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation (exons 5-8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33).
1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student's t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The -1p/-19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss.
rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the -1p/-19q genotype.
伴有或不伴有-1p/-19q基因型的少突胶质细胞瘤中，导致化疗反应差异的生物学因素尚不清楚，但肿瘤血管生成可能起一定作用。我们旨在确定动态磁敏感对比增强（DSC）磁共振成像（MRI）是否能够区分少突胶质细胞瘤的分子亚型，并研究相对脑血容量（rCBV）与丙卡巴肼、洛莫司汀和长春新碱（PCV）化疗后预后之间的关系。
计算治疗前rCBV，并评估观察者间和观察者内的变异性。确定1p36、19q13、17p13、10p12 - 15和10q22 - 26的等位基因失衡以及p53突变（第5 - 8外显子）。将rCBV与基因型、临床病理特征（n = 37）以及PCV化疗后的预后（n = 33）进行比较。
在6/9例二级少突胶质细胞瘤、6/14例二级少突星形细胞瘤、4/4例三级少突胶质细胞瘤和3/10例三级少突星形细胞瘤中观察到1p/19q缺失。rCBV测量具有良好的观察者间和观察者内变异性，但无法区分组织学亚型或分级。1p/19q缺失的肿瘤rCBV值较高（Student t检验P = 0.001）。受试者工作特征分析显示，识别基因型的临界值为1.59（敏感性92%，特异性76%）。rCBV高和低的肿瘤对化疗均有反应。-1p/-19q基因型而非rCBV与PCV化疗后的反应、无进展生存期和总生存期密切相关。与1p/19q完整且rCBV低或rCBV高且1p/19q缺失的肿瘤相比，rCBV高且1p/19q完整的肿瘤患者无进展生存期和总生存期较短。
rCBV可识别出1p/19q缺失的少突胶质细胞瘤，但不能预测化疗敏感性。rCBV的预后意义在伴有或不伴有-1p/-19q基因型的少突胶质细胞瘤中可能有所不同。
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