title: Lactate dehydrogenase 5 expression in non-Hodgkin B-cell lymphomas is associated with hypoxia regulated proteins.
abstract: The expression of lactate dehydrogenase 5 (LDH5), the major LDH isoenzyme sustaining the anaerobic transformation glycolysis was examined in B-cell non-Hodgkin lymphomas. Multi-tissue slides obtained from patients with diffuse large B-cell lymphomas (DLBCL; 95 cases), follicular lymphomas (FL; 49 cases) and from non-neoplastic lymph nodes (48 cases) were used for immuhistochemical analysis. High LDH5 expression (cytoplasmic and nuclear) was noted in 79/95 and 29/49 cases of DLBCL and FL, respectively (p = 0.002). No expression was noted in non-neoplastic lymphocytes. In DLBCL, LDH5 expression was significantly related to hypoxia inducible factor HIF1alpha, HIF2alpha, vascular endothelial growth factor (VEGF) and phosphorylated vascular endothelial growth factor receptor 2 (VEGFR2/KDR) expression. In FL, however, a significant relation was confirmed with pVEGFR2/KDR and HIF2alpha. FL cases with the highest microvessel density were those, which lacked both LDH5 and VEGF expression. It is concluded that LDH5 is highly upregulated in B-cell non-Hodgkin lymphomas and is in direct relation to HIFs expression. LDH5 expression is linked with activated VEGFR2/KDR expression in both lymphoid lesions.
authors.affiliation: Department of Pathology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: Francesco
authors.initials: F
authors.lastname: Pezzella
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
authors.forename: Helen
authors.initials: H
authors.lastname: Turley
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Gatter
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000235:genetics*; D000080864:Lactate Dehydrogenase 5; D016393:Lymphoma, B-Cell / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D040301:Vascular Endothelial Growth Factor Receptor-2