Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma

Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma
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DOI:
10.1097/00000478-200404000-00005
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发表时间:
2004-04-01
影响因子:
5.6
通讯作者:
Perkins, SL
Perkins, SL
中科院分区:
医学1区
文献类型:
--
作者:
Chang, CC;McClintock, S;Perkins, SL

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最近的研究表明,基因表达谱类似于生发中心(GC)B细胞的弥漫性大B细胞淋巴瘤(DLBCL)病例比基因表达谱类似于活化B细胞的DLBCL病例预后好得多。本研究的目的是评估通过免疫组化使用一组GC B细胞(CD 10和Bcl-6)和活化(MUM 1/IRF 4和CD 138)标志物是否可定义新发DLBCL患者的预后。对42例原发DLBCL患者的石蜡包埋组织进行上述标记物的免疫组化染色。所有患者的中位随访时间为41个月(范围:1-103个月),存活患者的中位随访时间为65个月(范围:14-103个月)。这些病例可分为三种表达模式:表达CD 10和/或Bcl-6但不表达活化标志物的GC B细胞模式(模式A);表达至少一种GC B细胞标志物和一种活化标志物的活化GC B细胞模式(模式B);和表达MUM 1/IRF 4和/或CD 138但不表达GC B细胞标志物的活化非GC B细胞模式(模式C)。A型患者的总生存率明显高于其他两型患者(Kaplan-Meier生存分析,P < 0.008,log rank检验)。采用多因素考克斯比例风险回归分析,国际预后指数评分和这些标志物的表达模式是独立的预后指标。我们的研究结果表明,这组GC B细胞和活化标记物的表达模式与DLBCL患者的预后相关。石蜡包埋组织的免疫组化分析比基因表达谱的cDNA微阵列更容易获得,并可能提供类似的预后信息。
Recent studies with cDNA microarrays showed that diffuse large B-cell lymphoma (DLBCL) cases with gene expression profiles similar to germinal center (GC) B cells had much better prognosis than DLBCL cases with gene expression profiles resembling activated B cells. The goal of the current study is to evaluate if using a panel of GC B-cell (CD10 and Bcl-6) and activation (MUM1/IRF4 and CD138) markers by immunohistochemistry defines prognosis in patients with de novo DLBCL. Immunohistochermical stains for the above markers were performed on paraffin-embedded tissues from 42 de novo DLBCL patients. Median follow-up in all patients was 41 months (range, 1-103 months) and in surviving patients was 65 months (range, 14-103 months). These cases could be classified into three expression patterns: GC B-cell pattern (pattern A) expressing CD10 and/or Bcl-6 but not activation markers; activated GC B-cell pattern (pattern B) expressing at least one of GC B-cell markers and one of activation markers; and activated non-GC B-cell pattern (pattern C) expressing MUM1/IRF4 and/or CD138 but not GC B-cell markers. Patients with pattern A had much better overall survival than those with the other two patterns (Kaplan-Meier survival analysis, P < 0.008, log rank test). Using multivariate Cox proportional hazards regression analysis, the international prognostic index scores and the expression pattern of these markers were independent prognostic indicators. Our results suggest that expression patterns of this panel of GC B-cell and activation markers by immunohistochemistry correlate with the prognosis of patients with DLBCL. Immunohistochemical analysis on paraffin-embedded tissues is more readily available than gene expression profiling by cDNA microarray and may provide similar prognostic information.