Hans Christine P, Weisenburger Dennis D, Greiner Timothy C, Chan Wing C, Aoun Patricia, Cochran Gregory T, Pan Zenggang, Smith Lynette M, Lynch James C, Bociek Robert Gregory, Bierman Philip J, Vose Julie M, Armitage James O
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
Mod Pathol. 2005 Oct;18(10):1377-84. doi: 10.1038/modpathol.3800434.
We sought to determine whether identification of poor-risk subgroups of diffuse large B-cell lymphoma (DLBCL) using immunohistochemical stains would have practical utility with regard to prognosis and therapeutic decisions. Tissue microarray blocks were created using replicate samples of formalin-fixed, paraffin-embedded tissue from 200 cases of de novo DLBCL. The sections were stained with antibodies to proteins that are expressed by activated or proliferating B cells including MUM1, FOXP1, bcl-2, survivin, protein kinase C-beta (PKC-beta), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P = 0.025) or PKC-beta (P = 0.015) was associated with a worse overall survival, whereas none of the other markers was predictive of overall survival. Patients with DLBCL that expressed either cyclin D2 or PKC-beta had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P = 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-beta was an independent predictor of poor overall survival (P = 0.035). Cyclin D2 and PKC-beta expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.
我们试图确定使用免疫组织化学染色法识别弥漫性大B细胞淋巴瘤（DLBCL）的高危亚组对于预后和治疗决策是否具有实际效用。利用200例初发性DLBCL的福尔马林固定、石蜡包埋组织的重复样本制作组织微阵列块。切片用针对活化或增殖B细胞表达的蛋白质的抗体进行染色，这些蛋白质包括MUM1、FOXP1、bcl-2、生存素、蛋白激酶C-β（PKC-β）、细胞周期蛋白D2、细胞周期蛋白D3和Ki-67。在单变量分析中，细胞周期蛋白D2（P = 0.025）或PKC-β（P = 0.015）的肿瘤表达与较差的总生存期相关，而其他标志物均不能预测总生存期。与两种标志物均为阴性的患者52%的5年总生存率相比，表达细胞周期蛋白D2或PKC-β的DLBCL患者的5年总生存率仅为30%（P = 0.0019）。在多变量分析中，细胞周期蛋白D2或PKC-β的表达是总生存期差的独立预测因子（P = 0.035）。细胞周期蛋白D2和PKC-β的表达将有助于为DLBCL患者设计一个“生物学预后指数”。
