CD68、cyclin D 1蛋白和 bcl-6基因在弥漫性大 B 细胞淋巴瘤中的表达及意义
Expression of CD68, cyclin D1 and rearrangement of bcl-6 gene are adverse prognostic factors in diffuse large B-cell lymphoma
摘要目的:探讨CD68、cyclin D1蛋白表达及bcl-6基因重排对弥漫性大B细胞淋巴瘤(DLBCL)预后的影响。方法选取105例有详细随访资料的DLBCL患者石蜡样本,应用免疫组织化学EnVision法进行CD3、CD10、CD20、CD68、cyclin D1、bcl-6、MUM 1、SOX-11免疫标记,根据Han′s分类方法将DLBCL分为生发中心B细胞型( GCB型)和非生发中心B细胞型( non-GCB型);应用荧光原位杂交( FISH)技术检测bcl-6基因重排。应用统计软件分析CD68蛋白、cyclin D1蛋白、bcl-6基因、化疗方案及各临床因素与生存期之间的关系。分别以GCB型、non-GCB型免疫表型和CHOP、R-CHOP化疗方案分组,比较疗效差异。结果105例患者中GCB 型19例(18.1%), non-GCB 型86例(81.9%),CD68高表达18例(17.1%),cyclin D1高表达36例(34.3%)。 bcl-6基因重排21例(21.9%),CD68高表达、cyclin D1高表达与bcl-6基因重排三者之间无相关关系(P>0.05);单因素分析发现年龄≤60岁、临床分期Ⅰ~Ⅱ期、IPI评分0~2分、乳酸脱氢酶( LDH)<245 IU/L、GCB型、R-CHOP治疗方案患者的预后较好(P<0.05),性别、原发部位与预后无相关关系(P>0.05)。 CD68、cyclin D1高表达、bcl-6重排者预后不良( P<0.05);分层结果显示GCB型或non-GCB型CD68高表达对比同种免疫表型组都具有较差的预后,non-GCB型时cyclin D1高表达和bcl-6基因重排的预后不佳(P<0.01,P=0.02);治疗方案分层分析得出,在使用CHOP方案治疗时,CD68、cyclin D1高表达预后较差( P<0.05), R-CHOP 方案时, CD68、cyclin D1高表达与总生存期的差异无统计学意义(P=0.428和0.168)。多因素COX模型分析显示CD68高表达(P=0.026)、cyclin D1高表达(P=0.003)及LDH高水平(P=0.005)为各自独立的预后不良因素。结论 CD68、cyclin D1高表达和bcl-6基因重排提示预后差,CD68、cyclin D1蛋白和bcl-6基因可以作为与DLBCL患者预后指标。
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abstractsObjective To study expression of CD68, cyclin D1 protein and rearrangement of bcl-6 gene impact on the prognosis of diffuse large B-cell lymphoma ( DLBCL).Methods Gets paraffin samples of the 105 cases DLBCL with the detailed follow-up information , and were studied by using immunohistochemical EnVision method for CD 3, CD10, CD20, CD68, cyclin D1, bcl-6, MUM 1, SOX-11 immunolabeling.The DLBCL were classified into germinal center B cell-like ( GCB ) subtypes and non-germinal center B cell-like ( non-GCB) subtypes according to Hans′algorithm.Application of fluorescence in situ hybridization ( FISH ) technique to detect the bcl-6 gene rearrangement.The relationship between CD68, cyclin D1 protein, the bcl-6 gene and the curative effect of chemotherapy and survival was analyzed using statistical software.Respectively by GCB type , non-GCB type immune phenotype and CHOP , R-CHOP chemotherapy group , compare the curative effects.Results 105 patients had GCB 19 cases ( 18.1%) , non-GCB 86 cases ( 81.9%) , CD68 expression was 18 cases ( 17.1%) , cyclin D1 high expression 36 cases ( 34.3%) , bcl-6 gene rearrangement in 21 cases ( 21.9%) , there is no correlation among the three (P>0.05).One-way analysis of variance showed that age ≤60 years, clinical stageⅠ-Ⅱ, IPI score 0 to 2 points, LDH (U/L) <245 IU/L,GCB subtypes,R-CHOP therapy, the prognosis of patients with better (P<0.05), But gender, primary site no correlation with prognosis (P>0.05).CD68,cyclin D1 high expression , bcl-6 rearrangement had poor prognosis ( P <0.05 ).Stratification analysis results show GCB-type or non-GCB type with high expression of CD 68 contrast alloimmune phenotype groups had a poor prognosis,non-GCB type with high expression of cyclin D 1 and rearrangement of bcl-6 gene had a poor prognosis(P<0.001,P=0.02).Treatment scheme of layered display ,the CHOP treatment, significantly correlated with overall survival with high expression of CD 68, cyclin D1 ( P <0.05 ), the R-CHOP treatment, there was no statistically significant difference between CD 68, cyclin D1 high expression and overall survival ( P=0.428 and 0.168 ).Multivariate COX model analysis showed that high expression of CD68 (P=0.026), high expression of cyclin D1 (P=0.003) and high levels of LDH (P=0.005) were adverse prognostic factors independent.Conclusions high expression of CD68, cyclin D1 and rearrangement of bcl-6 gene suggests poor prognosis ,CD68, cyclin D1 protein and bcl-6 gene can be used as a prognostic indicator in patients with DLBCL .
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