Activation of the NF-κB signalling pathway in diffuse large B-cell lymphoma: Clinical implications

Aim: To characterize the activation of the nuclear factor (NF)-κB pathway in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry. Methods and results: Sixty-six DLBCLs treated with anthracycline-containing chemotherapy were evaluated with antibodies against phosphorylated p65 (P-p65), p65, p50, p52, IKKα, and phosphorylated IκB (P-IκB). NF-κB activation was based on the expression of P-p65, P-IκB, and nuclear expression of p65 or p52 in the tumour cells. P-p65 and P-IκB were expressed in 13 (20%) and 17 cases (26%), respectively. p65, p52 and IKKα were found in the cytoplasm. A correlation was found between expression of P-p65 and P-IκB (P < 0.0001), but not between the two subtypes of DLBCL [germinal centre B cell and non-germinal centre (GC)]. P-p65+ tumours showed a better response to chemotherapy (P = 0.025) and a trend to increased event-free survival (P = 0.08). However, P-IκB expression was not associated with either clinical response or survival. Bcl-2 was not preferentially expressed on DLBCL tumours with NF-κB activation, as determined by expression of P-p65 and P-IκB proteins. Conclusions: NF-κB activation in DLBCL is preferentially mediated through the classical pathway and a novel mechanism involving phosphorylation of p65. Activation of NF-κB by P-p65 is associated with good prognosis. NF-κB activation is not confined to non-GC DLBCL exclusively. © 2008 The Authors.