多重打击弥漫性大B细胞淋巴瘤的检测及其临床病理学研究

发布时间：2018-01-10 22:19

  本文关键词：多重打击弥漫性大B细胞淋巴瘤的检测及其临床病理学研究　出处：《遵义医学院》2016年硕士论文　论文类型：学位论文

  更多相关文章： 弥漫性大B细胞淋巴瘤 多重打击 MYC BCL-2 BCL-6 易位 免疫表型 荧光原位杂交 临床病理 预后

【摘要】：目的：多重打击弥漫性大B细胞淋巴瘤是一种以分子遗传学特点命名的高度侵袭性的弥漫性大B细胞淋巴瘤。该类肿瘤的发病率低,临床病理特点复杂,预后差。由于多重打击弥漫性大B细胞淋巴瘤对DA-EPOCH-R化疗方案具有较好反应,因此很有必要将其及时检出,指导临床治疗。本研究通过对DLBCL样本相关蛋白的检测,再结合分子遗传学技术检测出多重打击弥漫性大B细胞淋巴瘤,并探讨其临床病理学特征。方法：本研究共收集四川省人民医院病理科诊断为DLBCL病例374例,经两位资深淋巴瘤专家进行重新阅片,最后筛选出满足实验条件的病例348例。病理诊断标准参照2008版造血与淋巴组织肿瘤WHO分类。免疫组织化学(IHC)检测采用EnVision二步法,对所选样本进行了c-MYC、CD10、BCL-6、MUM-1、BCL-2、CD5、Ki-67等蛋白的检测。]DLBCL的免疫分型采用Hans分型。采用组织原位杂交(ISH)方法检测EB病毒编码的小分子RNA (EBER)。采用荧光原位杂交(FISH)方法对c-MYC蛋白阳性病例进行MYC基因易位的检测,并对MYC基因易位病例再行BCL-2和BCL-6基因易位的FISH检测。对348例病例进行了临床资料的收集及随访,最后结合临床资料、随访结果及实验结果进行综合统计学分析。结果：1、MHL检测结果：(1)348例DLBCL中,c-MYC蛋白阳性178例(51.1%),BCL-2蛋白阳性288例(82.8%)；c-MYC和BCL-2蛋白共同表达的双表达淋巴瘤(DEL)158例(45.4%)；BCL-6蛋白阳性134例(38.5%)。(2)348例DLBCL中,47例(13.5%)存在MYC基因易位,单打击淋巴瘤(SHL)6例(1.7%),双重打击淋巴瘤(DHL)36例(10.3%),三重打击淋巴瘤(THL)5例(1.4%)。2、MHL的临床病理学特征：(1)47例MHL患者中位年龄为62岁,年龄分布为19岁～82岁。(2)女性多于男性,男女性别比为1：1.25。(3)淋巴结内25例(53.2%),淋巴结外22例(46.8%)。(4)就诊时多数(86.1%)患者处于Ann Arbor临床分期Ⅲ期～Ⅳ期,75%的患者血清乳酸脱氢酶(LDH)水平不同程度升高,47.1%的患者伴随B症状,69.4%的患者国际预后指数(IPI)评分为3分～5分。(5)组织形态学分型：中心母细胞型39例(83%),免疫母细胞型8例(17%)。(6)免疫表型：CD10阳性21例(44.7%)BCL-6阳性22例(46.8%); Mum-1阳性14例(29.8%)；Ki-67PI中位百分率为70%,≥60% 38例(80.9%)；c-MYC/BCL-2双表达病例46例(97.9%)。(7) Hans分型：GCB型33例(70.2%),Non-GCB型14例(29.8%),比例为2.36：1。(8)EBV原位杂交检测：EBER阳性18例(38.3%)。(9)治疗及生存分析：36例有随访资料的患者中16例(44.5%)仅行手术治疗,20例(55.5%)行手术联合化疗,化疗方案包括CHOP方案、R-CHOP方案、DA-EPOCH-R方案。随访1个月～64个月,中位生存时间6±1.1个月,平均生存时间11.5±2.1个月,存活5例(13.9%),死亡31例(86.1%)。结论：(1)多重打击DLBCL是一类少见的具有独特临床意义的侵袭性淋巴瘤。(2)IHC是初筛DLBCL中MHL的有效工具,FISH是验证MHL的金标准,IHC结合FISH检测的方法简单实用,适用于临床普查。(3)MHL以女性多见,多发于淋巴结内,Ann Arbor I临床分期晚,LDH水平高,IPI评分高,Hans分型以GCB型为主,Ki-67PI高,EBV感染阳性率相对较高。(4) Ann Arbor I临床分期晚、GCB亚型、BCL-2阳性、EBV感染阳性是MHL患者的独立影响因素。(5)MHL较非MHL患者治疗效果差、预后差。(6)MHL较DEL患者预后差,DEL较非DEL患者预后差。
[Abstract]:Objective: to combat multiple diffuse large B cell lymphoma is a name on the molecular genetics characteristics of highly invasive diffuse large B cell lymphoma. The tumor incidence rate is low, the clinical pathological characteristics of complex and poor prognosis. The multiple impact of diffuse large B cell lymphoma has a better response to DA-EPOCH-R chemotherapy, therefore it is necessary to timely detection, to guide the clinical treatment. This study through the detection of samples of DLBCL related protein, combined with molecular genetics technology to detect multiple impact of diffuse large B cell lymphoma, and to explore its clinical pathological features. Methods: This study collected the pathology department of Sichuan Provincial People's Hospital diagnosed 374 cases of DLBCL, the two senior experts for re reading lymphoma, finally selected to meet the experimental conditions of 348 cases. The pathological diagnosis standard of 2008 edition of hematopoietic and lymphoid tissue tumor WHO tumor classification. Immunohistochemistry (IHC) detected by EnVision two step method, the selected samples were c-MYC, CD10, BCL-6, MUM-1, BCL-2, CD5,.]DLBCL, Ki-67 and other immune detection protein typing by Hans genotyping. In situ hybridization (ISH) with small molecular RNA method for detection of EB virus the encoding (EBER). By using fluorescence in situ hybridization (FISH) detection method for MYC gene translocation of c-MYC protein positive cases, FISH detection of MYC gene translocation cases and re translocation of BCL-2 and BCL-6 genes. Of 348 cases were collected and follow-up clinical data, finally combined with clinical data, follow-up study the experimental results and comprehensive statistics. Results: 1, the results of MHL (1): 348 cases of DLBCL, c-MYC protein was positive in 178 cases (51.1%), BCL-2 protein was positive in 288 cases (82.8%); the co expression of c-MYC and BCL-2 protein expression (DEL) double lymphoma in 158 cases (45.4%); BC L-6铔嬬櫧闃虫，

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