Takano Shingo, Hattori Keiichiro, Ishikawa Eiichi, Narita Yoshitaka, Iwadate Yasuo, Yamaguchi Fumio, Nagane Motoo, Akimoto Jiro, Oka Hidehiro, Tanaka Satoshi, Sakata Mamiko, Matsuda Masahide, Yamamoto Tetsuya, Chiba Shigeru, Matsumura Akira
Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
World Neurosurg. 2018 Apr;112:e69-e73. doi: 10.1016/j.wneu.2017.12.028. Epub 2017 Dec 16.
Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88 L265P mutation, which is related to NF-κB signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor.
Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88 L265P mutation was evaluated by polymerase chain reaction and direct sequencing.
The MyD88 L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88 L265P mutation nor age >65 years alone significantly predicted overall survival relative to MyD88 wild type and age <65. The MyD88 L265P mutation was predominantly present in patients aged >65 years. Among age >65 patients, the MyD88 L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P < 0.04).
The MyD88 L265P mutation predicted a poor prognosis in elderly PCNSL patients. A new tailor-made treatment strategy might be needed for these patients.
近期对原发性中枢神经系统淋巴瘤（PCNSL）的基因分析表明，与核因子κB（NF-κB）信号传导相关的髓样分化因子88（MyD88）L265P突变是PCNSL的基因标志；因此，它可作为诊断的基因标志物和分子治疗的潜在靶点。然而，MyD88突变在PCNSL中的作用尚未明确。在本研究中，我们调查了多个机构中接受治疗的PCNSL患者的MyD88突变情况及其临床特征，以确定其作为预后因素的意义。
本研究纳入了来自8个机构的41例PCNSL（弥漫性大B细胞型）患者。他们的中位年龄为68岁；中位随访时间为26.7个月；中位总生存期为26.7个月；1年、3年和5年生存率分别为75.6%、58.5%和43.9%。从冷冻组织中提取脱氧核糖核酸，通过聚合酶链反应和直接测序评估MyD88 L265P突变。
41例患者中有61.0%（25/41）检测到MyD88 L265P突变。Kaplan-Meier分析显示，相对于MyD88野生型和年龄<65岁的患者，单独的MyD88 L265P突变或年龄>65岁均不能显著预测总生存期。MyD88 L265P突变主要出现在年龄>65岁的患者中。在年龄>65岁的患者中，与MyD88野生型相比，MyD88 L265P突变预示着更差的总生存期（11.5个月对56.2个月，P<0.04）。
MyD88 L265P突变预示老年PCNSL患者预后不良。可能需要为这些患者制定新的个性化治疗策略。
