Sippl Christoph, Urbschat Steffi, Kim Yoo Jin, Senger Sebastian, Oertel Joachim, Ketter Ralf
Department of Neurosurgery, University of Saarland, Faculty of Medicine, Homburg/Saar, D-66424 Homburg, Germany.
Institute of Neuropathology, University of Saarland, Faculty of Medicine, Homburg/Saar, D-66424 Homburg, Germany.
Oncol Lett. 2018 Feb;15(2):1600-1606. doi: 10.3892/ol.2017.7490. Epub 2017 Nov 24.
Promoter methylation of , , RB transcriptional corepressor 1 () and O-6-methylguanine-DNA methyltransferase () impacts the prognosis of numerous glioma subtypes. However, whether promoter methylation of these genes also has an impact on the clinical course of pilocytic astrocytoma remains unclear. Using methylation-specific polymerase chain reaction, the methylation status of the tumor suppressor genes , , , and in pilocytic astrocytomas (n=18) was analyzed. Immunohistochemical staining for the R132H mutation of the isocitrate dehydrogenase (NADP(+)) 1, cytosolic () gene was performed. Clinical data including age, gender, localization of tumor, extent of resection, treatment modality, progression-free survival and overall survival were collected. The methylation index for , , and was 0.0, 0.0, 5.6% (1/18) and 44.5% (8/18), respectively. If the promoter was methylated, the probability of relapse and second subsequent therapy was significantly increased (P=0.019). The one patient with methylation of demonstrated a poor clinical course. The pilocytic astrocytomas of all 18 patients revealed wild-type . Clinically, there was a significant correlation of subtotal resection with the occurrence of relapse (P=0.005) and of the localization of the tumor with the extent of resection (P=0.031). Gross total resection was achieved significantly more often in pediatric patients than in adult patients (P=0.003). Adult patients demonstrated more relapses following the first tumor resection (P=0.001). The present study indicates that methylation of is associated with a poor clinical course and represents an age-independent risk factor for an unfavorable outcome. Other influential factors of outcome were the age of the patient and extent of resection.
、、视网膜母细胞瘤转录共抑制因子1（RB1）和O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的启动子甲基化影响多种胶质瘤亚型的预后。然而，这些基因的启动子甲基化是否也对毛细胞型星形细胞瘤的临床病程有影响仍不清楚。采用甲基化特异性聚合酶链反应，分析了18例毛细胞型星形细胞瘤中肿瘤抑制基因、、、和的甲基化状态。对异柠檬酸脱氢酶（NADP(+)）1（IDH1）基因的R132H突变进行免疫组织化学染色。收集包括年龄、性别、肿瘤定位、切除范围、治疗方式、无进展生存期和总生存期在内的临床数据。、、和的甲基化指数分别为0.0、0.0、5.6%（1/18）和44.5%（8/18）。如果MGMT启动子发生甲基化，复发和后续二次治疗的概率会显著增加（P=0.019）。1例发生MGMT甲基化的患者临床病程较差。18例患者的毛细胞型星形细胞瘤均显示IDH1野生型。临床上，次全切除与复发的发生有显著相关性（P=0.005），肿瘤定位与切除范围有显著相关性（P=0.031）。小儿患者实现全切除的比例明显高于成人患者（P=0.003）。成人患者首次肿瘤切除后复发更多（P=0.001）。本研究表明，MGMT甲基化与不良临床病程相关，是一个与年龄无关的不良预后危险因素。其他影响预后的因素是患者年龄和切除范围。
