Department of Neurosurgery, Nagoya University, Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
J Neurooncol. 2010 Jul;98(3):341-8. doi: 10.1007/s11060-009-0078-z. Epub 2009 Dec 13.
Several biomarkers have been identified as prognostic factors in primary central nervous system lymphoma (PCNSL). However, the correlation between the histogenetic origin of PCNSL and the response to therapy is still unclear. To elucidate the utility of immunophenotypic markers in predicting clinical outcomes, we investigated 27 immunocompetent patients with PCNSL treated with high-dose methotrexate therapy. Of the 27 patients, 25 received whole-brain radiotherapy after high-dose methotrexate. Immunostaining for CD5, CD10, BCL-6, and MUM-1 was used to determine the immunophenotypic profile of diffuse large B-cell lymphoma of PCNSL. We then evaluated whether immunophenotypic markers were associated with the response to therapy or patients' survival. The response to induction high-dose methotrexate therapy was determined by magnetic resonance imaging after three courses of i.v. high-dose methotrexate. We categorized B-cell lymphomas into three known subtypes: germinal center B-cell (GCB), activated-GCB, and post-GCB subtypes according to immunohistochemical profile. All the BCL-6-positive samples were co-positive for MUM-1 and therefore classified into activated-GCB subtype. BCL-6 expression in this study was associated with poor progression-free survival (P = 0.038). No immunophenotypic markers or subtypes had a significant effect on the response to high-dose methotrexate therapy. However, the response itself was a significant predictor for both progression-free survival (P < 0.001) and overall survival (P = 0.003). Further investigation is needed to assess BCL-6 as a potential prognostic factor in PCNSL.
已经有几种生物标志物被确定为原发性中枢神经系统淋巴瘤（PCNSL）的预后因素。然而，PCNSL 的组织发生起源与治疗反应之间的相关性尚不清楚。为了阐明免疫表型标志物在预测临床结果方面的作用，我们研究了 27 例接受大剂量甲氨蝶呤治疗的免疫功能正常的 PCNSL 患者。在这 27 例患者中，25 例在大剂量甲氨蝶呤治疗后接受全脑放疗。我们使用 CD5、CD10、BCL-6 和 MUM-1 的免疫染色来确定 PCNSL 的弥漫性大 B 细胞淋巴瘤的免疫表型特征。然后，我们评估了免疫表型标志物是否与治疗反应或患者的生存相关。诱导性大剂量甲氨蝶呤治疗的反应通过静脉注射大剂量甲氨蝶呤三个疗程后的磁共振成像来确定。我们根据免疫组织化学特征将 B 细胞淋巴瘤分为三个已知亚型：生发中心 B 细胞（GCB）、活化-GCB 和后-GCB 亚型。所有 BCL-6 阳性样本均与 MUM-1 共阳性，因此被归类为活化-GCB 亚型。本研究中 BCL-6 的表达与无进展生存期（P = 0.038）较差相关。没有免疫表型标志物或亚型对大剂量甲氨蝶呤治疗的反应有显著影响。然而，反应本身是无进展生存期（P < 0.001）和总生存期（P = 0.003）的显著预测因素。需要进一步研究来评估 BCL-6 作为 PCNSL 的潜在预后因素。
