弥漫大B细胞淋巴瘤患者蛋白表达检测的预后意义  

Prognostic significance of proteins expression by immunohistochemical method in diffuse large B cell lymphoma

作　　者：俞文娟[1] 曹利红 王敬瀚[1] 王照明[1] 钱文斌[1] 佟红艳[1] 孟海涛[1] 麦文渊[1] 毛莉萍[1] 钱劼靖[1] 金洁[1] 

机构地区：[1]浙江大学医学院附属第一医院,杭州310003

出　　处：《中华血液学杂志》2017年第9期784-788,共5页Chinese Journal of Hematology

摘　　要：目的探讨TP53、Bcl-2、Bcl-6、Myc蛋白表达对弥漫大B细胞淋巴瘤（DLBcL）患者预后的影响。方法回顾性分析223例DLBCL患者的临床资料，对有完整病理资料患者的石蜡标本采用免疫组化法进行TP53、Bcl-2、Bcl-6、Myc蛋白表达检查，并结合临床资料进行预后影响因素分析。结果①223例患者中男133例，女90例，中位发病年龄为56（15～83）岁。所有患者均进行TP53、Myc、Bcl-2、Bcl-6蛋白检测，阳性率分别为39．0％、38．6％、69．1％、56．5％，Myc／Bcl-2双表达22．7％（64／223）；按照Hans分型分类，生发中心起源B细胞亚型（GCB型）占27．4％，non-GCB占72．6％。②进一步分析发现TP53蛋白表达组non—GCB亚型居多（81．6％对66．9％,P=0．021），且与Myc表达存在显著正相关（P〈0．001）。③219例患者获得完整随访资料，中位随访时间为38（2～97）个月，3、5年总生存（OS）率分别为70％、66％。单因素分析结果显示Bcl-6蛋白表达为预后良好因素（P=0．034），TP53高表达（P=0．007）、Myc／Bcl-2双表达（P=0．012）为预后不良因素。多因素分析结果显示TP53高表达（HR=1．848，95％CI 1．025-2．968，P=0．010）及Myc／Bcl-2双表达（HR=1．124，95％C11．134～2．256，P=0．032）为独立预后不良因素。④TP53阳性与阴性组患者3年OS率分别为59％和77％，5年OS率分别为57％和71％，差异均有统计学意义（P值均〈0．05）。结论免疫组化法检测Mye／Bcl-2双表达及TP53高表达能够预测DLBCL患者的预后,Myc／Bcl-2双表达及TP53高表达是DLBCL患者的独立预后不良因素。Objective To analyze the prognostic significance ofTP53, Bcl-2, Bcl-6, Myc proteins expression by immunohistochemical method （IHC） in diffuse large B cell Lymphoma （DLBCL）. Methods Clinical and pathologic data of 223 patients with DLBCL hospitalized in Zhejiang First Hospital from March 2009 to June 2015 were retrospectively analyzed. Results The 223 cases, a median age of 56 years old with a male predominance, had shown a 39.0% of TP53 positive expression, 38.6% of Myc, 69.1% of Bcl-2, 56.5% of Bcl-6, and 22.7% of Myc/Bcl-2 double expression. According to Hans＇ classification, 27.4% were GCB and 72.6% were non-GCB. With a median follow-up of 38 （2-97） months, the 3 and 5 years survival rates were 70% and 66%, respectively. By multivariate analysis, TP53 over- expression and Myc/Bcl-2 double expression were independently associated with poor outcomes. 3-year and 5-year overall survival were 59% and 57% for patients with TP53 positive, 77% and 71% for patientswith TP53 negative expression. Patients with non-GCB subtype receiving chemotherapy combined with rituximab had a higher OS than those without rituximab. But rituximab did not improve the prognosis of patients with TP53 positive. Conclusion Myc/Bcl-2 double expression and TP53 over-expression are poor prognosis for DLBCL patients. Patients with Myc/Bcl-2 double expression have shorter OS. Patients with non-GCB subtype who received chemotherapy combined with rituximab have a better OS than those without rituximab. But rituximab does not improve the prognosis of patients with TP53 positive.

关 键 词：淋巴瘤 大B细胞 弥漫性 肿瘤抑制蛋白质P53 原癌基因蛋白质c—myc 原癌 基因蛋白质c-bcl-2 预后 

分 类 号：R446.1[医药卫生—诊断学] R733[医药卫生—临床医学]