Clinicopathological implications of nuclear factor κB signal pathway activation in diffuse large B-cell lymphoma

Hum Pathol. 2015 Apr;46(4):524-31. doi: 10.1016/j.humpath.2014.06.032. Epub 2014 Sep 21.

Abstract

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.

Keywords: Diffuse large B lymphoma; NF-κB pathway; P-p65; Prognosis; p52.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Prognosis
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Survival Rate

Substances

  • NF-kappa B