title: Serum levels of inflammatory cytokines at diagnosis correlate to the bcl-6 and CD10 defined germinal centre (GC) phenotype and bcl-2 expression in patients with diffuse large B-cell lymphoma.
abstract: Circulating inflammatory cytokines have a prognostic impact independent of the information provided by the International Prognostic Index (IPI) in diffuse large B-cell lymphoma (DLBCL). The present study characterized prognostic cytokines in relation to stage-specific B-cell differentiation antigens and bcl-2 protein expression, assessed by immunohistochemistry in de novo DLBCL. Serum levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were found to be significantly lower in patients with a germinal centre (GC) phenotype (co-expression of bcl-6 and CD10) compared with the non-GC phenotype. IL-6 and TNF-alpha levels were significantly elevated in patients expressing bcl-2 protein. Serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were not associated with the GC phenotype. On the contrary, both VEGF and bFGF were strongly correlated to bcl-2 expression. In survival analysis, IPI score remained the most important independent prognostic factor. However, IL-6 and VEGF, combined with non-GC phenotype and bcl-2 positivity, respectively, had a similar independent prognostic power as the IPI. In conclusion, our data suggest that inflammatory cytokines are differently distributed in the GC and non-GC phenotypes and correlate to bcl-2 expression. Combining these biomarkers may add to the prognostic information given by clinical variables in the IPI alone.
authors.affiliation: Department of Haematology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. lampe@herlevhosp.kbhamt.dk
authors.forename: Lars M
authors.initials: LM
authors.lastname: Pedersen
authors.forename: Gitte W
authors.initials: GW
authors.lastname: Jürgensen
authors.forename: Hans E
authors.initials: HE
authors.lastname: Johnsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000097:blood*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D015260:Neprilysin