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染色体臂1p和19q的改变作为少突胶质细胞瘤、星形细胞瘤和混合性少突星形细胞瘤生存的预测指标。

Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas.

作者信息

Smith J S, Perry A, Borell T J, Lee H K, O'Fallon J, Hosek S M, Kimmel D, Yates A, Burger P C, Scheithauer B W, Jenkins R B

机构信息

Division of Laboratory Genetics, Division of Anatomic Pathology, Department of Neurology, and Section of Biostatistics, Mayo Clinic and Foundation, Rochester, MN 55905, USA.

出版信息

J Clin Oncol. 2000 Feb;18(3):636-45. doi: 10.1200/JCO.2000.18.3.636.

Abstract

PURPOSE

A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas.

PATIENTS AND METHODS

Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors.

RESULTS

The oligodendroglial phenotype was highly associated with loss of 1p (P =.0002), loss of 19q (P <.0001), and combined loss of 1p and 19q (P <.0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma (log-rank, P =.03) and remained a significant predictor after adjusting for the effects of patient age and tumor grade (P <.01). This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma.

CONCLUSION

Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management.

摘要

目的

最近的一份报告表明,1号染色体短臂(1p)和19号染色体长臂(19q)的改变与接受丙卡巴肼、洛莫司汀和长春新碱化疗的间变性少突胶质细胞瘤患者的化疗反应及总生存期相关。我们着手在更广泛的弥漫性胶质瘤(包括星形细胞瘤和低级别少突胶质细胞瘤)中进一步阐明这些改变的诊断和预后意义。

患者与方法

在162例弥漫性胶质瘤(79例星形细胞瘤、52例少突胶质细胞瘤和31例混合性少突星形细胞瘤)中,对映射到1p和19q常见缺失区域的DNA探针的荧光原位杂交(FISH)信号进行计数,这些病例是作为一项正在进行的中枢神经系统肿瘤前瞻性研究的一部分收集的。

结果

少突胶质细胞表型与1p缺失(P = 0.0002)、19q缺失(P < 0.0001)以及1p和19q联合缺失(P < 0.0001)高度相关。1p和19q联合缺失被确定为纯少突胶质细胞瘤患者总生存期延长的单变量预测因子(对数秩检验,P = 0.03),在调整患者年龄和肿瘤分级的影响后,它仍然是一个显著的预测因子(P < 0.01)。这种有利关联在星形细胞瘤或混合性少突星形细胞瘤患者中并不明显。

结论

1p和19q联合缺失是纯少突胶质细胞瘤患者生存期延长的统计学显著预测因子,与肿瘤分级无关。鉴于星形细胞瘤患者缺乏这种关联以及先前证明的少突胶质细胞瘤的化疗敏感性,组织学和基因型评估相结合的方法可能会改善现有的患者分层和管理策略。

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