Activation of the NF-kappaB signalling pathway in diffuse large B-cell lymphoma: clinical implications.
OBJECTIVE
To characterize the activation of the nuclear factor (NF)-kappaB pathway in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry.


RESULTS
Sixty-six DLBCLs treated with anthracycline-containing chemotherapy were evaluated with antibodies against phosphorylated p65 (P-p65), p65, p50, p52, IKK alpha, and phosphorylated I kappaB (P-I kappaB). NF-kappaB activation was based on the expression of P-p65, P-I kappaB, and nuclear expression of p65 or p52 in the tumour cells. P-p65 and P-I kappaB were expressed in 13 (20%) and 17 cases (26%), respectively. p65, p52 and IKK alpha were found in the cytoplasm. A correlation was found between expression of P-p65 and P-I kappaB (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-I kappaB expression was not associated with either clinical response or survival. Bcl-2 was not preferentially expressed on DLBCL tumours with NF-kappaB activation, as determined by expression of P-p65 and P-I kappaB proteins.


CONCLUSIONS
NF-kappaB activation in DLBCL is preferentially mediated through the classical pathway and a novel mechanism involving phosphorylation of p65. Activation of NF-kappaB by P-p65 is associated with good prognosis. NF-kappaB activation is not confined to non-GC DLBCL exclusively.
Espinosa
I
I
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain.
Briones
J
J
Bordes
R
R
Brunet
S
S
Martino
R
R
Sureda
A
A
Sierra
J
J
Prat
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D055815:Young Adult
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA