100例弥漫大B细胞淋巴瘤临床病理、分子遗传学改变及与预后相关性研究

发布时间：2018-03-30 12:32

  本文选题：弥漫大B细胞淋巴瘤　切入点：免疫表型　出处：《新疆医科大学》2014年硕士论文

【摘要】：目的：探讨100例弥漫大B细胞淋巴瘤临床病理改变及分子遗传学特征及其对预后的影响。以促进对DLBCL病理特征及分子遗传学改变的进一步认识，进而从分子水平了解DLBCL的发生、发展以及转归。方法：收集2007～2014年间由新疆医科大学第一附属医院收治经手术切除并由病理确诊的100例DLBCL病例。整理临床资料，参照2008版WHO造血与淋巴组织肿瘤分类诊断标准复查阅片。应用免疫组化（Envision二步法）观察CD3、CD5、CD10、CD20、CD23、CD34、CD43、Bcl-2、Bcl-6、MUM-1、CyclinD1、Ki-67的表达情况；应用原位杂交技术检测EBER；应用荧光原位杂交（FISH）技术检测100例DLBCL中BCL-2、BCL-6、C-myc基因的改变；结合临床病理资料进行统计分析，筛选影响100例DLBCL患者预后的危险因素。结果：本研究中DLBCL发病的高峰年龄为31～50岁，男性发病率略高于女性（男/女=1.27：1）；原发于淋巴结内患者59例。原发于结外器官的患者41例，其中以原发性中枢神经系统弥漫大B细胞淋巴瘤最为多见，为30例。临床分期中I-II期患者共49例，血清LDH水平升高27例，血清LDH水平（186.11±58.67）U/L；III-IV期患者共51例，，血清LDH水平升高25例，血清LDH水平（287.19±177.63）U/L， III-IV期患者血清LDH水平显著高于I-II期患者（P＜0.05）。B症状患者血清LDH水平(311.43±213.83)U/L，A症状患者血清LDH水平(231.79±119.33)U/L，B症状患者血清LDH水平显著高于A症状患者，P=0.02。I-II期患者中血清β2-MG水平增高34例，β2-MG水平(1705.35±505.66)ug/L， III-IV期患者中血清β2-MG水平增高44例，β2-MG水平(3207.53±1067.33)ug/L，III-IV期β2-MG水平显著高于I-II期，P0.05。B症状患者β2-MG水平(3133.52±1013.23)ug/L，A症状患者血清β2-MG (2055.31±955.67)ug/L， B症状患者β2-MG水平显著高于A症状患者，P0.05。形态学以中心母细胞型为主（92/100）。100例患者中CD3阳性7例（7.00%）、CD10阳性11例（11.00%）、CD20阳性94例（94.00%）、CD34阳性79例（79.00%）、Bcl-2阳性55例（55.00%）、Bcl-6阳性89例（89.00%）、MUM-1阳性75例（75.00%）。CD10蛋白表达与ECOG评分相关（P=0.003）。免疫表型：生发中心起源19例，非生发中心起源81例。5例EBER阳性，其中1例为GCB，4例为non-GCB。仅ESR与免疫学表型之间差异具有统计学意义（P=0.017）。5例EBER阳性均为中心母细胞型。FISH检测：Bcl-2/IgH基因融合1例，BCL-2基因扩增7例。BCL-6基因重排8例。C-myc基因重排2例。单因素生存分析显示：血清LDH水平、原发肿瘤大小、IPI评分及治疗效果等因素的生存时间差异具有统计学意义（P＜0.05），多因素Cox分析结果显示：血清LDH水平、原发肿瘤大小及治疗效果是影响DLBCL患者预后的独立因素。结论：本研究显示DLBCL发病以男性多见，结内起病多见；血清LDH增高的患者预后较差。且血清LDH升高与AnnArbor临床分期相关；血清β2-MG水平与AnnArbor临床分期相关，但与预后无关；DLBCL的组织学亚型以中心母细胞型最常见；单因素生存分析显示：血清LDH水平、原发肿瘤大小、IPI评分及治疗效果等因素对预后的影响差异具有统计学意义（P＜0.05）。患者发病年龄、性别、民族、是否存在B症状、临床分期、ECOG评分、治疗方式、Bcl-2蛋白表达、Bcl-6蛋白表达及基因突变等因素的生存时间差异无统计学意义（P＞0.05）；Cox多因素分析显示：血清LDH水平、原发肿瘤大小及治疗效果是影响DLBCL患者预后的独立因素。
[Abstract]:Objective: To investigate 100 cases of diffuse large B cell lymphoma in clinical pathology and molecular genetics characteristics and its influence on the prognosis. In order to promote the further understanding of the pathological changes and molecular genetics characteristics of DLBCL, and then from the molecular level understanding of DLBCL occurrence, development and prognosis. Methods: collected 2007~2014 years from the First Affiliated Hospital of Xinjiang Medical University by surgery resection and 100 cases of DLBCL diagnosed by pathology. Organize the clinical data, according to the 2008 edition of the WHO classification of hematopoietic and lymphoid tissue tumor diagnosis standard review reading. Immunohistochemistry (Envision two steps) to observe CD3, CD5, CD10, CD20, CD23, CD34, CD43, Bcl-2, Bcl-6, MUM-1, CyclinD1, expression Ki-67; in situ hybridization was used to detect EBER; fluorescence in situ hybridization (FISH) technique to detect BCL-2 in 100 cases of DLBCL BCL-6, the change of C-myc gene with clinicopathological data; For statistical analysis, screening of risk factors affecting the prognosis of patients with DLBCL 100 cases. Results: in this study DLBCL the peak age of onset was 31~50 years, the incidence of male was higher than female (male / female =1.27:1); primary lymph nodes in 59 patients. 41 patients of primary extranodal organs, including in primary CNS diffuse large B cell lymphoma is the most common, 30 cases of patients with clinical stage I-II. A total of 49 cases, 27 cases with elevated serum LDH level, serum LDH level (186.11 + 58.67) U/L; III-IV patients with a total of 51 cases, 25 cases with elevated serum LDH levels, serum LDH the level of (287.19 + 177.63) U/L, LDH in serum III-IV level was significantly higher than I-II patients (P < 0.05).B symptoms in patients with serum LDH level (311.43 + 213.83) U/L, A in serum of patients with symptoms of LDH level (231.79 + 119.33) U/L, B in serum of patients with symptoms of LDH were significantly higher than that of patients with symptoms of A, P=0.02.I-II 鏈熸偅鑰呬腑琛

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