多重打擊彌漫性大B細胞淋巴瘤的檢測及其臨床病理學(xué)研究
發(fā)布時間:2018-01-10 22:19
本文關(guān)鍵詞:多重打擊彌漫性大B細胞淋巴瘤的檢測及其臨床病理學(xué)研究 出處:《遵義醫(yī)學(xué)院》2016年碩士論文 論文類型:學(xué)位論文
更多相關(guān)文章: 彌漫性大B細胞淋巴瘤 多重打擊 MYC BCL-2 BCL-6 易位 免疫表型 熒光原位雜交 臨床病理 預(yù)后
【摘要】:目的:多重打擊彌漫性大B細胞淋巴瘤是一種以分子遺傳學(xué)特點命名的高度侵襲性的彌漫性大B細胞淋巴瘤。該類腫瘤的發(fā)病率低,臨床病理特點復(fù)雜,預(yù)后差。由于多重打擊彌漫性大B細胞淋巴瘤對DA-EPOCH-R化療方案具有較好反應(yīng),因此很有必要將其及時檢出,指導(dǎo)臨床治療。本研究通過對DLBCL樣本相關(guān)蛋白的檢測,再結(jié)合分子遺傳學(xué)技術(shù)檢測出多重打擊彌漫性大B細胞淋巴瘤,并探討其臨床病理學(xué)特征。方法:本研究共收集四川省人民醫(yī)院病理科診斷為DLBCL病例374例,經(jīng)兩位資深淋巴瘤專家進行重新閱片,最后篩選出滿足實驗條件的病例348例。病理診斷標(biāo)準(zhǔn)參照2008版造血與淋巴組織腫瘤WHO分類。免疫組織化學(xué)(IHC)檢測采用EnVision二步法,對所選樣本進行了c-MYC、CD10、BCL-6、MUM-1、BCL-2、CD5、Ki-67等蛋白的檢測。]DLBCL的免疫分型采用Hans分型。采用組織原位雜交(ISH)方法檢測EB病毒編碼的小分子RNA (EBER)。采用熒光原位雜交(FISH)方法對c-MYC蛋白陽性病例進行MYC基因易位的檢測,并對MYC基因易位病例再行BCL-2和BCL-6基因易位的FISH檢測。對348例病例進行了臨床資料的收集及隨訪,最后結(jié)合臨床資料、隨訪結(jié)果及實驗結(jié)果進行綜合統(tǒng)計學(xué)分析。結(jié)果:1、MHL檢測結(jié)果:(1)348例DLBCL中,c-MYC蛋白陽性178例(51.1%),BCL-2蛋白陽性288例(82.8%);c-MYC和BCL-2蛋白共同表達的雙表達淋巴瘤(DEL)158例(45.4%);BCL-6蛋白陽性134例(38.5%)。(2)348例DLBCL中,47例(13.5%)存在MYC基因易位,單打擊淋巴瘤(SHL)6例(1.7%),雙重打擊淋巴瘤(DHL)36例(10.3%),三重打擊淋巴瘤(THL)5例(1.4%)。2、MHL的臨床病理學(xué)特征:(1)47例MHL患者中位年齡為62歲,年齡分布為19歲~82歲。(2)女性多于男性,男女性別比為1:1.25。(3)淋巴結(jié)內(nèi)25例(53.2%),淋巴結(jié)外22例(46.8%)。(4)就診時多數(shù)(86.1%)患者處于Ann Arbor臨床分期Ⅲ期~Ⅳ期,75%的患者血清乳酸脫氫酶(LDH)水平不同程度升高,47.1%的患者伴隨B癥狀,69.4%的患者國際預(yù)后指數(shù)(IPI)評分為3分~5分。(5)組織形態(tài)學(xué)分型:中心母細胞型39例(83%),免疫母細胞型8例(17%)。(6)免疫表型:CD10陽性21例(44.7%)BCL-6陽性22例(46.8%); Mum-1陽性14例(29.8%);Ki-67PI中位百分率為70%,≥60% 38例(80.9%);c-MYC/BCL-2雙表達病例46例(97.9%)。(7) Hans分型:GCB型33例(70.2%),Non-GCB型14例(29.8%),比例為2.36:1。(8)EBV原位雜交檢測:EBER陽性18例(38.3%)。(9)治療及生存分析:36例有隨訪資料的患者中16例(44.5%)僅行手術(shù)治療,20例(55.5%)行手術(shù)聯(lián)合化療,化療方案包括CHOP方案、R-CHOP方案、DA-EPOCH-R方案。隨訪1個月~64個月,中位生存時間6±1.1個月,平均生存時間11.5±2.1個月,存活5例(13.9%),死亡31例(86.1%)。結(jié)論:(1)多重打擊DLBCL是一類少見的具有獨特臨床意義的侵襲性淋巴瘤。(2)IHC是初篩DLBCL中MHL的有效工具,FISH是驗證MHL的金標(biāo)準(zhǔn),IHC結(jié)合FISH檢測的方法簡單實用,適用于臨床普查。(3)MHL以女性多見,多發(fā)于淋巴結(jié)內(nèi),Ann Arbor I臨床分期晚,LDH水平高,IPI評分高,Hans分型以GCB型為主,Ki-67PI高,EBV感染陽性率相對較高。(4) Ann Arbor I臨床分期晚、GCB亞型、BCL-2陽性、EBV感染陽性是MHL患者的獨立影響因素。(5)MHL較非MHL患者治療效果差、預(yù)后差。(6)MHL較DEL患者預(yù)后差,DEL較非DEL患者預(yù)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铔嬬櫧闃蟲,
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