Immunohistochemical expression of angiogenic cytokines and their receptors in reactive benign lymph nodes and non-Hodgkin lymphoma.
Angiogenic cytokines regulate B-cell lymphopoiesis and are related to prognosis in B-cell lymphoproliferative disorders. Transforming growth factor-beta (TGF-beta) inhibits mature B-cell proliferation and immunoglobulin production. Increased levels of serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are associated with poor prognosis in non-Hodgkin lymphoma (NHL). To understand the expression of angiogenic cytokines at different stages of B-cell differentiation in lymph nodes, we examined the immunohistochemical expression of TGF-beta, VEGF, bFGF, and their receptors in five patients with reactive benign lymphadenopathy and 12 patients with B-cell NHL (mantle cell lymphoma, 4; small cleaved cell follicular lymphoma, 5; lymphoplasmacytic lymphoma, 3). In benign lymph nodes, TGF-beta1, TGF-beta2, and TGFbetaRII were positive in prefollicular mantle cells, follicular center cells, and postfollicular plasma cells. Basic FGF, FGF-R1, and FGF-R4 were positive in large follicular center cells and postfollicular plasma cells. Vascular endothelial growth factor was positive in large follicular center cells and postfollicular plasma cells. In NHL, TGF-beta and its receptors were weakly positive in small cleaved cell follicular lymphoma; VEGF was strongly positive in lymphoplasmacytic lymphoma and weakly positive in mantle cell lymphoma. Basic FGF and its receptors were negative in NHL; however, FGF-R4 was positive in some cases of small cleaved cell follicular lymphoma. Our findings suggest that TGF-beta, bFGF, and their receptors have opposite roles in B-cell differentiation and maturation in benign lymph nodes. Transforming growth factor-beta and its receptors have an important role in germinal center development; loss of their activity could be associated with abnormal clonal proliferation of NHL.
Ho
Ching-Liang
CL
Division of Hematopathology, Mayo Clinic, Rochester, MN 55905, USA.
Sheu
Lai-Fa
LF
Li
Chin-Yang
CY
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D018121:Receptors, Cytokine / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016207:Cytokines; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D018121:Receptors, Cytokine; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2