Braaten Kristina M, Betensky Rebecca A, de Leval Laurence, Okada Yoshifumi, Hochberg Fred H, Louis David N, Harris Nancy L, Batchelor Tracy T
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Clin Cancer Res. 2003 Mar;9(3):1063-9.
The purpose of this study was to investigate the histogenetic origin of primary central nervous system lymphoma (PCNSL) with respect to stage of B-cell differentiation and to identify prognostic markers in a cohort of patients with PCNSL treated with i.v. high-dose methotrexate therapy.
This study included 33 patients with PCNSL treated with high-dose i.v. methotrexate at the Massachusetts General Hospital for whom archival tumor tissue was available. All 33 patients tested negative for HIV. The lymphomas were morphologically subclassified according to the Kiel system, as modified in the WHO classification. Immunohistochemistry for the following antigens was performed: BCL-6; BCL-2; MUM1; CD10; vs38c; CD138; CD44; p16; and p53. Fluorescence in situ hybridization and multiplex PCR for CDKN2A/p16 were also performed.
There were 17 women and 16 men enrolled, with a median age of 60 years. All tumors were diffuse large B-cell lymphomas. Of the 23 cases that could be subclassified, 22 were centroblastic, and 1 was immunoblastic. Twenty-six of 33 tumors were BCL-6+, 6 of 32 tumors were CD10+, 27 of 29 tumors were BCL-2+, 31 of 32 tumors were MUM1+, 11 of 31 tumors were CD44+, 4 of 33 tumors were vs38c+, and 0 of 32 tumors were CD138+. There were 18 of 32 (56%) complete responses and 8 of 32 (25%) partial responses to methotrexate, whereas 6 of 33 (18%) progressed during treatment. Ten patients died of disease. Expression of BCL-6 was significantly associated with longer overall survival (P = 0.002; median survival, 101 versus 14.7 months, with approximately 95% lower confidence limits of 41.7 and 8.8 months, respectively).
In this group of 33 patients with PCNSL, expression of BCL-6 was significantly associated with longer overall survival. BCL-6 warrants further investigation as a potentially important prognostic marker in this disease.
本研究旨在探讨原发性中枢神经系统淋巴瘤（PCNSL）在B细胞分化阶段的组织发生起源，并在一组接受静脉高剂量甲氨蝶呤治疗的PCNSL患者中识别预后标志物。
本研究纳入了33例在麻省总医院接受高剂量静脉甲氨蝶呤治疗且有存档肿瘤组织的PCNSL患者。所有33例患者HIV检测均为阴性。淋巴瘤根据WHO分类修订后的Kiel系统进行形态学亚分类。对以下抗原进行免疫组织化学检测：BCL-6、BCL-2、MUM1、CD10、vs38c、CD138、CD44、p16和p53。还进行了CDKN2A/p16的荧光原位杂交和多重PCR检测。
入组患者中17例为女性，16例为男性，中位年龄60岁。所有肿瘤均为弥漫性大B细胞淋巴瘤。在可亚分类的23例病例中，22例为中心母细胞性，1例为免疫母细胞性。33例肿瘤中26例BCL-6阳性，32例肿瘤中6例CD10阳性，29例肿瘤中27例BCL-2阳性，32例肿瘤中31例MUM1阳性，31例肿瘤中11例CD44阳性，33例肿瘤中4例vs38c阳性，32例肿瘤中0例CD138阳性。对甲氨蝶呤治疗有18例（56%）完全缓解，8例（25%）部分缓解，而33例中有6例（18%）在治疗期间病情进展。10例患者死于疾病。BCL-6的表达与更长的总生存期显著相关（P = 0.002；中位生存期分别为101个月和14.7个月，约95%置信下限分别为41.7个月和8.8个月）。
在这组33例PCNSL患者中，BCL-6的表达与更长的总生存期显著相关。BCL-6作为该疾病潜在的重要预后标志物值得进一步研究。
