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100例彌漫大B細(xì)胞淋巴瘤臨床病理、分子遺傳學(xué)改變及與預(yù)后相關(guān)性研究

發(fā)布時(shí)間:2018-03-30 12:32

  本文選題:彌漫大B細(xì)胞淋巴瘤 切入點(diǎn):免疫表型 出處:《新疆醫(yī)科大學(xué)》2014年碩士論文


【摘要】:目的:探討100例彌漫大B細(xì)胞淋巴瘤臨床病理改變及分子遺傳學(xué)特征及其對(duì)預(yù)后的影響。以促進(jìn)對(duì)DLBCL病理特征及分子遺傳學(xué)改變的進(jìn)一步認(rèn)識(shí),進(jìn)而從分子水平了解DLBCL的發(fā)生、發(fā)展以及轉(zhuǎn)歸。方法:收集2007~2014年間由新疆醫(yī)科大學(xué)第一附屬醫(yī)院收治經(jīng)手術(shù)切除并由病理確診的100例DLBCL病例。整理臨床資料,參照2008版WHO造血與淋巴組織腫瘤分類診斷標(biāo)準(zhǔn)復(fù)查閱片。應(yīng)用免疫組化(Envision二步法)觀察CD3、CD5、CD10、CD20、CD23、CD34、CD43、Bcl-2、Bcl-6、MUM-1、CyclinD1、Ki-67的表達(dá)情況;應(yīng)用原位雜交技術(shù)檢測(cè)EBER;應(yīng)用熒光原位雜交(FISH)技術(shù)檢測(cè)100例DLBCL中BCL-2、BCL-6、C-myc基因的改變;結(jié)合臨床病理資料進(jìn)行統(tǒng)計(jì)分析,篩選影響100例DLBCL患者預(yù)后的危險(xiǎn)因素。結(jié)果:本研究中DLBCL發(fā)病的高峰年齡為31~50歲,男性發(fā)病率略高于女性(男/女=1.27:1);原發(fā)于淋巴結(jié)內(nèi)患者59例。原發(fā)于結(jié)外器官的患者41例,其中以原發(fā)性中樞神經(jīng)系統(tǒng)彌漫大B細(xì)胞淋巴瘤最為多見(jiàn),為30例。臨床分期中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水平顯著高于I-II期患者(P<0.05)。B癥狀患者血清LDH水平(311.43±213.83)U/L,A癥狀患者血清LDH水平(231.79±119.33)U/L,B癥狀患者血清LDH水平顯著高于A癥狀患者,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水平顯著高于I-II期,P0.05。B癥狀患者β2-MG水平(3133.52±1013.23)ug/L,A癥狀患者血清β2-MG (2055.31±955.67)ug/L, B癥狀患者β2-MG水平顯著高于A癥狀患者,P0.05。形態(tài)學(xué)以中心母細(xì)胞型為主(92/100)。100例患者中CD3陽(yáng)性7例(7.00%)、CD10陽(yáng)性11例(11.00%)、CD20陽(yáng)性94例(94.00%)、CD34陽(yáng)性79例(79.00%)、Bcl-2陽(yáng)性55例(55.00%)、Bcl-6陽(yáng)性89例(89.00%)、MUM-1陽(yáng)性75例(75.00%)。CD10蛋白表達(dá)與ECOG評(píng)分相關(guān)(P=0.003)。免疫表型:生發(fā)中心起源19例,非生發(fā)中心起源81例。5例EBER陽(yáng)性,其中1例為GCB,4例為non-GCB。僅ESR與免疫學(xué)表型之間差異具有統(tǒng)計(jì)學(xué)意義(P=0.017)。5例EBER陽(yáng)性均為中心母細(xì)胞型。FISH檢測(cè):Bcl-2/IgH基因融合1例,BCL-2基因擴(kuò)增7例。BCL-6基因重排8例。C-myc基因重排2例。單因素生存分析顯示:血清LDH水平、原發(fā)腫瘤大小、IPI評(píng)分及治療效果等因素的生存時(shí)間差異具有統(tǒng)計(jì)學(xué)意義(P<0.05),多因素Cox分析結(jié)果顯示:血清LDH水平、原發(fā)腫瘤大小及治療效果是影響DLBCL患者預(yù)后的獨(dú)立因素。結(jié)論:本研究顯示DLBCL發(fā)病以男性多見(jiàn),結(jié)內(nèi)起病多見(jiàn);血清LDH增高的患者預(yù)后較差。且血清LDH升高與AnnArbor臨床分期相關(guān);血清β2-MG水平與AnnArbor臨床分期相關(guān),但與預(yù)后無(wú)關(guān);DLBCL的組織學(xué)亞型以中心母細(xì)胞型最常見(jiàn);單因素生存分析顯示:血清LDH水平、原發(fā)腫瘤大小、IPI評(píng)分及治療效果等因素對(duì)預(yù)后的影響差異具有統(tǒng)計(jì)學(xué)意義(P<0.05);颊甙l(fā)病年齡、性別、民族、是否存在B癥狀、臨床分期、ECOG評(píng)分、治療方式、Bcl-2蛋白表達(dá)、Bcl-6蛋白表達(dá)及基因突變等因素的生存時(shí)間差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);Cox多因素分析顯示:血清LDH水平、原發(fā)腫瘤大小及治療效果是影響DLBCL患者預(yù)后的獨(dú)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?zhèn)h呬腑琛

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