原发中枢神经系统弥漫性大B细胞淋巴瘤中bcl-2、C—MYC基因异常、蛋白表达及治疗方案选择对患者预后的影响  

Survival of patients with primary central nervous system diffuse large B-cell lymphoma： impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens

作　　者：尹文娟[1,3] 朱秀 杨海燕[2] 孙文勇[1] 吴梅娟[1] 

机构地区：[1]浙江省肿瘤医院病理科,杭州310022 [2]浙江省肿瘤医院淋巴瘤内科,杭州310022 [3]浙江省头颈肿瘤转化医学研究重点实验室

出　　处：《中华病理学杂志》2018年第1期32-38,共7页Chinese Journal of Pathology

摘　　要：目的 探讨原发中枢神经系统（PCNS）弥漫性大B细胞淋巴瘤（DLBCL）临床病理学特点,分析其中bcl-6、bcl-2、C-MYC基因异常、蛋白表达及治疗方案选择对患者预后的影响.方法 收集浙江省肿瘤医院2007年1月至2016年12月收治的33例PCNS-DLBCL患者资料,对33例患者样本进行免疫组织化学（IHC）染色以检测CD10、bcl-2、bcl-6、MUM1、MYC蛋白表达;原位杂交检测肿瘤组织中EB病毒编码的小RNA（EBER）;荧光原位杂交（FISH）检测bcl-6、bcl-2、C-MYC基因扩增及易位情况;利用单、双因素生存分析及 Cox 风险回归模型分析上述指标改变与预后的关系.结果33例患者,男女比为1.36：1.00,平均年龄56岁.20例为单发病灶,13例为多发病灶;12例累犯深部脑组织.所有患者接受部分或全部肿瘤切除,5例术后接受全脑放疗,9例接受高剂量甲氨蝶呤为基础的化疗,12例接受全脑放疗联合高剂量甲氨蝶呤为基础的化疗,7例未进一步治疗,8例患者在化疗时联合使用利妥昔单抗.按照 Hans 模型分类非生发中心型（non-GCB）27例（81.8%,27/33）.25例（75.8%,25/33）bcl-2蛋白表达阳性,其中8例（24.2%）为高表达（≥70%）,12例（36.4%） C-MYC蛋白表达阳性（≥40%）,C-MYC和bcl-2蛋白双表达者有6例（18.2%,6/33）.EBER阳性率为10.0%（3/30）.28例患者中检测到5例bcl-6基因异常;7例bcl-2基因异常;4例C-MYC基因异常,bcl-2、C-MYC基因同时发生异常（＂双打击＂）者2例（7.4%）.13例患者发现脑脊液中蛋白升高, 10例血中乳酸脱氢酶升高.随访时间2~90个月,平均生存时间（23.0 ± 3.7）个月,2年生存率为39.0%.单因素分析发现bcl-2蛋白高表达、MYC蛋白阳性、bcl-2基因异常是PCNS-DLBCL的不良预后指标,以高剂量甲氨蝶呤为基础的化疗、利妥昔单抗的应用为良性预后因素,双因素分析发现bcl-2、MYC蛋白双表达及bcl-2、C-MYC基因双打击为PCNS-DLBCL的不良预后因素.Cox多因素风险�Objective To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6,bcl-2,C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma（PCNS-DLBCL）. Methods Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining（IHC）. The presence of EB virus was detected by in situ hybridization （EBER）. Copy number variation（ICN）and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization（FISH）. The relationship between the above indexes and the prognosis was analyzed by univariate,bivariate survival analysis and multiple Cox hazard regression analysis. Results The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36 ：1.00,and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate（HD-MTX）based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model,27 cases were classified as non-GCB subtypes（81.8%）. Bcl-2 was positive in 25 cases（75.8%,25/33）and highly expressed in 8（24.2%）. MYC was positive in 12 cases（36.4%）and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%（3/30）, all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation

关 键 词：中枢神经系统肿瘤 淋巴瘤 大B-细胞 弥漫性 基因 MYC 原癌基因蛋白质 c—myc 预后 bcl-2蛋白 

分 类 号：R739.4[医药卫生—肿瘤]