Chang Chung-Che, McClintock Sara, Cleveland Ronald P, Trzpuc Trent, Vesole David H, Logan Brent, Kajdacsy-Balla Andre, Perkins Sherrie L
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Am J Surg Pathol. 2004 Apr;28(4):464-70. doi: 10.1097/00000478-200404000-00005.
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. Immunohistochemical 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.
近期利用cDNA微阵列进行的研究表明，基因表达谱与生发中心（GC）B细胞相似的弥漫性大B细胞淋巴瘤（DLBCL）病例的预后明显好于基因表达谱类似于活化B细胞的DLBCL病例。本研究的目的是评估通过免疫组织化学使用一组GC B细胞（CD10和Bcl-6）和活化（MUM1/IRF4和CD138）标志物是否能确定初发性DLBCL患者的预后。对42例初发性DLBCL患者石蜡包埋组织进行上述标志物的免疫组织化学染色。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CD10和/或Bcl-6但不表达活化标志物的GC B细胞模式（A模式）；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（B模式）；表达MUM1/IRF4和/或CD138但不表达GC B细胞标志物的活化非GC B细胞模式（C模式）。A模式患者的总生存期明显好于其他两种模式的患者（Kaplan-Meier生存分析，P < 0.008，对数秩检验）。使用多变量Cox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。我们的结果表明，通过免疫组织化学检测这组GC B细胞和活化标志物的表达模式与DLBCL患者的预后相关。石蜡包埋组织的免疫组织化学分析比cDNA微阵列基因表达谱分析更容易获得，并且可能提供相似的预后信息。
