Zinzani Pier Luigi, Dirnhofer Stephan, Sabattini Elena, Alinari Lapo, Piccaluga Pier Paolo, Stefoni Vittorio, Tani Monica, Musuraca Gerardo, Marchi Enrica, Falini Brunangelo, Baccarani Michele, Pileri Stefano A
Pathologic Anatomy & Lymphoma Unit, Institute of Haematology and Medical Oncology L. & A. Seràgnoli, Bologna University, Bologna, Italy.
Haematologica. 2005 Mar;90(3):341-7.
Patients with diffuse large B-cell lymphoma (DLBCL) could benefit from integration of well-established bioclinical prognostic factors with new tools - such as micro-arrays - exploring aberrant gene and/or protein expression.
Tissue micro-arrays (TMA) were constructed for the paraffin blocks of 68 patients with de novo DLBCL with nodal presentation, who underwent MACOP-B and were provided with complete clinical information. TMA were tested with specific antibodies against CD10, CD20, CD30, CD79a, CD138, Bcl-2, Bcl-6, IRF4, and IRTA1.
The following phenotypic subclassification was made: a) CD10 +/Bcl-6 + or Bcl-6+/IRF4 +, but Bcl-2-/CD30-/CD138-- suggesting B-cells gathering/leaving the germinal center (group 1; n=36); b) Bcl-2+/CD10-/Bcl-6- and CD30+ or CD138+ corresponding to putative non-germinal center B-cells with features of activation or plasmablastic/plasmacellular differentiation (group 2; n=17); c) CD30-/CD138- with extensive Bcl-2 positivity and variable CD10, Bcl-6 and IRF4 combinations (group 3; n=15). Mean IPI scores were 0.6, 1.9 and 1.1 for groups 1, 2 and 3, respectively (p= 0.001). Complete remission (CR) rates were 89%, 53% and 73% (p= 0.015). The 3-year relapse-free survival (RFS) rates are 86%, 41% and 63% (p=0.001) and 42-month overall survival (OS) rates are 91%, 38% and 66% (p=0.0002).
The present TMA-based study suggests an immunophenotypic profiling system for patients with de novo DLBCL that seems to provide additional prognostic information and contributes to the existing debate on the identification of suitable immunohistochemical surrogates of gene expression profiling results.
弥漫性大B细胞淋巴瘤（DLBCL）患者可从将成熟的生物临床预后因素与探索异常基因和/或蛋白质表达的新工具（如微阵列）相结合中获益。
为68例初发有淋巴结表现的DLBCL患者的石蜡块构建组织微阵列（TMA），这些患者接受了MACOP - B治疗并提供了完整的临床信息。用抗CD10、CD20、CD30、CD79a、CD138、Bcl - 2、Bcl - 6、IRF4和IRTA1的特异性抗体检测TMA。
进行了以下表型亚分类：a）CD10 +/Bcl - 6 +或Bcl - 6+/IRF4 +，但Bcl - 2 -/CD30 -/CD138 -，提示B细胞聚集/离开生发中心（第1组；n = 36）；b）Bcl - 2 +/CD10 -/Bcl - 6 -且CD30 +或CD138 +，对应具有激活或浆母细胞/浆细胞分化特征的假定非生发中心B细胞（第2组；n = 17）；c）CD30 -/CD138 -，Bcl - 2广泛阳性，CD10、Bcl - 6和IRF4组合多样（第3组；n = 15）。第1、2和3组的平均国际预后指数（IPI）评分分别为0.6、1.9和1.1（p = 0.001）。完全缓解（CR）率分别为89%、53%和73%（p = 0.015）。3年无复发生存率（RFS）分别为86%、41%和63%（p = 0.001），42个月总生存率（OS）分别为91%、38%和66%（p = 0.0002）。
目前基于TMA的研究为初发DLBCL患者提出了一种免疫表型分析系统，该系统似乎能提供额外的预后信息，并有助于当前关于鉴定合适的基因表达谱结果免疫组化替代指标的争论。
