Obermann Ellen C, Went Philip, Pehrs Ann-Christine, Tzankov Alexandar, Wild Peter J, Pileri Stefano, Hofstaedter Ferdinand, Dirnhofer Stephan
Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
Oncol Rep. 2005 Dec;14(6):1461-7.
Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin's lymphoma in the Western world; it is characterized by marked genetic, morphological and clinical heterogeneity. The identification of prognostic markers could help to develop risk-adapted treatment strategies. As proliferation of cells is essential for tumour growth, analysis of the cell cycle and its individual phases might give additional information on tumour progression and clinical behaviour. To investigate the prognostic value of proteins specifically related to the cell cycle phases S, G2 and M in DLBCL, the expression of cyclin A as a marker of S phase and cyclin B1 as a G2/M phase marker were analysed in combination with other clinicopathological parameters in a large cohort of patients. Expression of cyclin B1 and cyclin A were determined by immunohistochemistry using tissue microarray methodology. Immunoreactivity for cyclin B1 and cyclin A was correlated with clinical data using a two-sided Fisher's exact test. Impact on overall survival was analysed by the Kaplan-Meier method. A negative prognostic impact was found for expression of cyclin B1. Nuclear and/or cytoplasmic staining in > or = 1% of tumour cells was significantly associated with shorter overall survival in the multivariate analysis (p=0.008). Furthermore, the prognostic impact of cyclin B1 expression was independent of the tumour stage. No prognostic significance was found for expression of cyclin A. In conclusion, this study demonstrates the independent prognostic value of an expression of cyclin B1 in DLBCL and proposes its evaluation as a prognostic marker in the assessment of this entity which is easily applicable in daily routine practice.
弥漫性大B细胞淋巴瘤（DLBCL）是西方世界最常见的非霍奇金淋巴瘤；其特征是具有显著的遗传、形态学和临床异质性。识别预后标志物有助于制定风险适应性治疗策略。由于细胞增殖对肿瘤生长至关重要，分析细胞周期及其各个阶段可能会提供有关肿瘤进展和临床行为的额外信息。为了研究与细胞周期S期、G2期和M期特异性相关的蛋白质在DLBCL中的预后价值，在一大群患者中，将细胞周期蛋白A作为S期标志物和细胞周期蛋白B1作为G2/M期标志物的表达与其他临床病理参数相结合进行分析。使用组织微阵列方法通过免疫组织化学测定细胞周期蛋白B1和细胞周期蛋白A的表达。使用双侧Fisher精确检验将细胞周期蛋白B1和细胞周期蛋白A的免疫反应性与临床数据相关联。通过Kaplan-Meier方法分析对总生存期的影响。发现细胞周期蛋白B1的表达具有负面预后影响。在多变量分析中，肿瘤细胞中≥1%的细胞核和/或细胞质染色与较短的总生存期显著相关（p=0.008）。此外，细胞周期蛋白B1表达的预后影响与肿瘤分期无关。未发现细胞周期蛋白A的表达具有预后意义。总之，本研究证明了细胞周期蛋白B1表达在DLBCL中的独立预后价值，并建议将其评估作为该实体评估中的预后标志物，这在日常临床实践中易于应用。
