Objective: To analyze the prognostic significance of TP53, Bcl-2, Bcl-6, Myc proteins expression by immunohistochemical method (IHC) in diffuse large B cell Lymphoma (DLBCL) . Methods: Clinical and pathologic data of 223 patients with DLBCL hospitalized in Zhejiang First Hospital from March 2009 to June 2015 were retrospectively analyzed. Results: The 223 cases, a median age of 56 years old with a male predominance, had shown a 39.0% of TP53 positive expression, 38.6% of Myc, 69.1% of Bcl-2, 56.5% of Bcl-6, and 22.7% of Myc/Bcl-2 double expression. According to Hans' classification, 27.4% were GCB and 72.6% were non-GCB. With a median follow-up of 38 (2-97) months, the 3 and 5 years survival rates were 70% and 66% , respectively. By multivariate analysis, TP53 over-expression and Myc/Bcl-2 double expression were independently associated with poor outcomes. 3-year and 5-year overall survival were 59% and 57% for patients with TP53 positive, 77% and 71% for patients with TP53 negative expression. Patients with non-GCB subtype receiving chemotherapy combined with rituximab had a higher OS than those without rituximab. But rituximab did not improve the prognosis of patients with TP53 positive. Conclusion: Myc/Bcl-2 double expression and TP53 over-expression are poor prognosis for DLBCL patients. Patients with Myc/Bcl-2 double expression have shorter OS. Patients with non-GCB subtype who received chemotherapy combined with rituximab have a better OS than those without rituximab. But rituximab does not improve the prognosis of patients with TP53 positive.
目的： 探讨TP53、Bcl-2、Bcl-6、Myc蛋白表达对弥漫大B细胞淋巴瘤（DLBCL）患者预后的影响。 方法： 回顾性分析223例DLBCL患者的临床资料，对有完整病理资料患者的石蜡标本采用免疫组化法进行TP53、Bcl-2、Bcl-6、Myc蛋白表达检查，并结合临床资料进行预后影响因素分析。 结果： ①223例患者中男133例，女90例，中位发病年龄为56（15～83）岁。所有患者均进行TP53、Myc、Bcl-2、Bcl-6蛋白检测，阳性率分别为39.0%、38.6%、69.1%、56.5%，Myc/Bcl-2双表达22.7%（64/223）；按照Hans分型分类，生发中心起源B细胞亚型（GCB型）占27.4%，non-GCB占72.6%。②进一步分析发现TP53蛋白表达组non-GCB亚型居多（81.6%对66.9%，P＝0.021），且与Myc表达存在显著正相关（P<0.001）。③219例患者获得完整随访资料，中位随访时间为38（2～97）个月，3、5年总生存（OS）率分别为70%、66%。单因素分析结果显示Bcl-6蛋白表达为预后良好因素（P＝0.034），TP53高表达（P＝0.007）、Myc/Bcl-2双表达（P＝0.012）为预后不良因素。多因素分析结果显示TP53高表达（HR＝1.848，95%CI 1.025～2.968，P＝0.010）及Myc/Bcl-2双表达（HR＝1.124，95%CI 1.134～2.256，P＝0.032）为独立预后不良因素。④TP53阳性与阴性组患者3年OS率分别为59%和77%，5年OS率分别为57%和71%，差异均有统计学意义（P值均<0.05）。 结论： 免疫组化法检测Myc/Bcl-2双表达及TP53高表达能够预测DLBCL患者的预后，Myc/Bcl-2双表达及TP53高表达是DLBCL患者的独立预后不良因素。.
Keywords: Lymphoma, large B cell, diffuse; Prognosis; Proto-oncogene proteins c-bcl-2; Proto-oncogene proteins c-myc; Tumor suppressor protein p53.