Nuclear factor-kappaB activation in primary lymphoma of bone

Abstract

Primary lymphoma of bone is a rare type of extranodal diffuse large B-cell lymphoma with a relatively favourable outcome. Recent scientific interest has focused on elucidating the role of nuclear factor-kappaB pathway in lymphomagenesis and its potential significance as a therapeutic target. In nodal B-cell non-Hodgkin lymphomas, constitutive activation of nuclear factor-kappaB appears to be involved in tumour cell survival, notably in the non-germinal centre type of diffuse large B-cell lymphoma. We investigated nuclear factor-kappaB activation via the classical and alternative pathway in primary lymphoma of bone, through immunohistochemical staining for nuclear factor-kappaB family members on tumour tissues of 50 patients. Nine cases (18 %) showed nuclear staining for p50, and one case showed nuclear co-expression of p52. None of the cases showed nuclear staining for c-Rel. The nuclear staining of p50 suggests that in a minority of primary lymphomas of bone nuclear factor-kappaB is constitutively activated via the classical pathway. In contrast to other extranodal types of diffuse large B-cell lymphoma, there was a lack of nuclear co-expression of p65, which might suggest activation of a different pathway. Activation of nuclear factor-kappaB through the alternative pathway does not appear to be significantly involved, as only one case showed significant nuclear expression for p52. Finally, nuclear expression of p50 was neither preferentially detected in non-germinal centre type or germinal centre type primary lymphoma of bone, nor related to poor prognosis. Therefore, in contrast to nodal diffuse large B-cell lymphoma, the nuclear factor-kappaB pathway does not appear to be an attractive therapeutic target in primary lymphoma of bone.