Zhao Qian, Fu Weijun, Jiang Hua, Du Juan, Zhang Chunyang, Xi Hao, Zhou Fan, Li Rong, Hou Jian
Department of Hematology, Myeloma and Lymphoma Center, Changzheng Hospital, Shanghai 200003, China.
Department of Hematology, Myeloma and Lymphoma Center, Changzheng Hospital, Shanghai 200003, China.
Hum Pathol. 2015 Apr;46(4):524-31. doi: 10.1016/j.humpath.2014.06.032. Epub 2014 Sep 21.
Although abnormal activation of the nuclear factor κB (NF-κB) signaling pathway plays an important role in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), only a few studies have dealt with the relation of NF-κB activation to clinical outcomes in this disease. We analyzed the clinical characteristics of 147 consecutive DLBCL patients, examined paraffin-embedded tissues from 120 of them to identify the activation of the NF-κB pathway by using immunohistochemical staining, and performed an overall survival (OS) analysis. Expression of P-p65 and p52 was found in 30.0% (n = 36) and 35.8% (n = 43) of the patients, respectively. Coexpression of these factors was found in 16.7% (n = 14) of the cases. Patients were divided into 4 groups according to P-p65 and/or p52 expression: P-p65(+) only, p52(+) only, both P-p65(+) and p52(+), and both P-p65(-) and p52(-). The 3-year OS rates in the 4 groups were 51.3%, 68.3%, 34.6%, and 85.8%, respectively (P = .006). Univariate analysis showed that early stage (P = .032), low International Prognostic Index score (P = .001), less than 2 extranodal metastases (P = .014), complete remission with chemotherapy (P < .0001), germinal-center B-cell-like subtype (P = .049), Ki-67 < 75% (P = .017), and P-p65(-) (P = .002) or p52(-) (P = .031) were associated with longer 3-year OS. Multivariate analysis indicated that P-p65 expression was an independent prognostic factor for shorter OS (P = .032). In conclusion, NF-κB pathway activation markers P-p65 and p52 predict poor survival in DLBCL patients.
尽管核因子κB（NF-κB）信号通路的异常激活在弥漫性大B细胞淋巴瘤（DLBCL）的发病机制中起重要作用，但仅有少数研究探讨了NF-κB激活与该疾病临床预后的关系。我们分析了147例连续的DLBCL患者的临床特征，对其中120例患者的石蜡包埋组织进行检查，通过免疫组化染色确定NF-κB通路的激活情况，并进行总生存（OS）分析。结果发现，分别有30.0%（n = 36）和35.8%（n = 43）的患者表达P-p65和p52。16.7%（n = 14）的病例中发现这两种因子共表达。根据P-p65和/或p52的表达情况将患者分为4组：仅P-p65(+)、仅p52(+)、P-p65(+)和p52(+)均阳性、P-p65(-)和p52(-)均阴性。4组患者的3年OS率分别为51.3%、68.3%、34.6%和85.8%（P = .006）。单因素分析显示，早期（P = .032）、国际预后指数评分低（P = .001）、结外转移少于2处（P = .014）、化疗后完全缓解（P < .0001）、生发中心B细胞样亚型（P = .049）、Ki-67<75%（P = .017）以及P-p65(-)（P = .002）或p52(-)（P = .031）与3年OS较长相关。多因素分析表明，P-p65表达是OS较短的独立预后因素（P = .032）。总之，NF-κB通路激活标志物P-p65和p52可预测DLBCL患者的不良生存。
