Prognostic factors for primary central nervous system lymphomas treated with high-dose methotrexate-based chemo-radiotherapy
Prognostic factors for primary central nervous system lymphomas treated with high-dose methotrexate-based chemo-radiotherapy
复制标题
大剂量甲氨蝶呤放化疗治疗原发性中枢神经系统淋巴瘤的预后因素
DOI：
10.1093/jjco/hyx098
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发表时间：
2017
影响因子：
2.4
通讯作者：
Nagane Motoo
中科院分区：
文献类型：
--
作者：
Lee Jeunghun;Shishido-Hara Yukiko;Suzuki Kaori;Shimizu Saki;Kobayashi Keiichi;Kamma Hiroshi;Shiokawa Yoshiaki;Nagane Motoo
背景：原发性中枢神经系统淋巴瘤（PCNSL）尽管采用高剂量甲氨蝶呤化疗，但仍是一种侵袭性和难治性肿瘤。年龄和运动状态是影响预后的重要临床因素，但影响预后的其他因素，尤其是分子因素仍不确定。方法研究41例以甲氨蝶呤为主的PCNSL患者的临床、神经影像学和免疫组织化学资料，评估潜在预后因素对临床预后的影响以及这些因素之间的相关性。中位无进展生存期（PFS）和总生存期（OS）分别为29个月和73个月。错配修复（MMR）蛋白MLH1、MSH2、MSH6和PMS2的表达紧密相关，MSH2的高表达与更好的OS和PFS显著相关（P= 0.005和P= 0.007），而甲氨蝶呤代谢相关蛋白不影响生存。此外，PMS2低表达是甲氨蝶呤耐药的独立预测因子（P= 0.039）。在神经影像学发现中，穹窿和被盖/掌受累与较差的OS （P< 0.001和P= 0.013）和PFS （P= 0.014和P= 0.043）显著相关。生发中心B细胞(GCB)-PCNSL亚型与非GCB亚型相比，具有更好的存活率。在癌基因方面，cmyc阳性患者OS较差（P= 0.046）。通过多变量分析，MSH2和穹窿累及是OS和PFS的独立预测因子，而被盖/腱膜位置和cMYC表达与OS显著相关。结论虽然还需要进一步的研究，但这些结果表明MMR蛋白的表达，以及特定的深部位置和cMYC的表达，可能是PCNSL的一种新的预后和预测指标。
BackgroundPrimary central nervous system lymphoma (PCNSL) remains an aggressive and refractory tumor despite high-dose methotrexate-based chemo-radiotherapy. Age and performance status have been shown to be important clinical prognostic factors, however others, especially molecular factors, affecting the prognosis are still uncertain.MethodsWe investigate clinical, neuroimaging and immunohistochemical data in tissue from 41 PCNSL patients treated primarily with methotrexate-based chemo-radiotherapy and evaluate the influence of potential prognostic factors on clinical outcome as well as correlation among these factors.ResultsMedian progression-free survival (PFS) and overall survival (OS) were 29 and 73 months, respectively. Expression of the mismatch repair (MMR) proteins, MLH1, MSH2, MSH6 and PMS2, correlated tightly with each other and high expression of MSH2 was significantly associated with better OS and PFS (P= 0.005 andP= 0.007), while methotrexate metabolism-related proteins did not affect survival. In addition, low expression of PMS2 was an independent predictor of methotrexate resistance (P= 0.039). Among neuroimaging findings, involvement of the fornix and tegmentum/velum were significantly associated with poorer OS (P< 0.001 andP= 0.013) and PFS (P= 0.014 andP= 0.043, respectively). Germinal center B cell (GCB)-PCNSL subtype as opposed to non-GCB subtype, tended toward better survival. Regarding oncogenes, cMYC-positive cases showed unfavorable OS (P= 0.046). By multivariate analysis, MSH2 and involvement of the fornix were independent predictors for both OS and PFS, whereas tegmentum/velum location and cMYC expression were significantly associated with OS.ConclusionsAlthough further studies are needed, these results suggest that MMR protein expression, as well as specific deep locations and cMYC expression, may be a novel prognostic and predictive markers for PCNSL.