Filipits Martin, Jaeger Ulrich, Pohl Gudrun, Stranzl Thomas, Simonitsch Ingrid, Kaider Alexandra, Skrabs Cathrin, Pirker Robert
Department of Internal Medicine I, Division of Oncology, University of Vienna, A-1090 Vienna, Austria.
Clin Cancer Res. 2002 Mar;8(3):729-33.
Cyclin D3 is an important regulator for transition from G(1) to the S phase of the cell cycle. Cyclin D3 expression is associated with cell proliferation in lymphoid tissues, but its impact on clinical outcome in non-Hodgkin's lymphomas has not been studied. Therefore, we determined the clinical relevance of cyclin D3 expression in patients with diffuse large B-cell lymphoma. We examined the relation between cyclin D3 expression at diagnosis and response to conventional polychemotherapy and overall survival in 81 previously untreated patients with diffuse large B-cell lymphoma. Cyclin D3 expression was assessed by immunohistochemistry. Cyclin D3 immunostaining ranged from 0-100% (median, 30%) of the lymphoma cells. Patients with high (>or=50% cyclin D3-positive lymphoma cells) cyclin D3 expression had a more advanced clinical stage (P = 0.003) and more often had extranodal disease in more than one site (P = 0.007) than patients with low cyclin D3 expression. Patients with high cyclin D3 expression had a significantly lower complete response rate (17% versus 74%; P < 0.001) and a shorter overall survival (3-year survival rate, 18% versus 74%; P < 0.001) than those with low cyclin D3 expression. Multivariate analyses that included cyclin D3 and the International Prognostic Index demonstrated that cyclin D3 expression had independent effects on the complete response rates and overall survival of the patients. In conclusion, high cyclin D3 expression is an independent predictive and prognostic factor associated with poor clinical outcome in patients with diffuse large B-cell lymphoma.
细胞周期蛋白D3是细胞周期从G(1)期向S期转变的重要调节因子。细胞周期蛋白D3的表达与淋巴组织中的细胞增殖相关，但尚未研究其对非霍奇金淋巴瘤临床结局的影响。因此，我们确定了弥漫性大B细胞淋巴瘤患者中细胞周期蛋白D3表达的临床相关性。我们研究了81例未经治疗的弥漫性大B细胞淋巴瘤患者诊断时细胞周期蛋白D3的表达与对传统多药化疗的反应及总生存期之间的关系。通过免疫组织化学评估细胞周期蛋白D3的表达。细胞周期蛋白D3免疫染色范围为淋巴瘤细胞的0 - 100%（中位数为30%）。与细胞周期蛋白D3低表达的患者相比，细胞周期蛋白D3高表达（≥50%细胞周期蛋白D3阳性淋巴瘤细胞）的患者临床分期更晚（P = 0.003），且更常出现多个部位的结外病变（P = 0.007）。细胞周期蛋白D3高表达的患者完全缓解率显著更低（17%对74%；P < 0.001），总生存期更短（3年生存率，18%对74%；P < 0.001）。纳入细胞周期蛋白D3和国际预后指数的多变量分析表明，细胞周期蛋白D3的表达对患者的完全缓解率和总生存期有独立影响。总之，细胞周期蛋白D3高表达是弥漫性大B细胞淋巴瘤患者临床结局差的独立预测和预后因素。
