title: Expression of angiogenic factors and hypoxia inducible factors HIF 1, HIF 2 and CA IX in non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Angiogenesis in solid tumour pathology is well established but less is known about its role in haematological malignancies. Our study investigated the immunohistochemical expression of a variety of angiogenic and hypoxic factors and microvessel densities on 110 cases of high- and low-grade non-Hodgkin's lymphomas and reactive lymphoid tissues. methods and results: Expression of vascular endothelial growth factor (VEGF) was present in 82 (96%) of the non-Hodgkin's cases and 35 (100%) of the reactive lymphoid tissue cases. Both hypoxia inducible factors 1 alpha and 2 alpha (HIF 1 alpha, 2 alpha) were weakly expressed in the majority of high- and low-grade lymphomas. Carbonic anhydrase IX (CA IX), a HIF-inducible membrane-bound enzyme, expression was not abundant with membranous staining being present in seven (8%) of the lymphoma cases and none of the reactive cases. Thymidine phosphorylase (TP) was distributed amongst macrophages and follicular dendritic cells but was not present in the neoplastic population. The vasculature was stained using CD34 which gave rise to a distinct vascular, predominantly paracortical network present in low-grade lymphomas and reactive lymphoid tissue but which was lost in high-grade lymphomas.
  
  
  CONCLUSIONS
  Our results suggest that non-Hodgkin's lymphomas may be less angiogenic and hypoxically driven than most solid tumours, which has implications for possible future therapies.
authors.affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Stewart
authors.forename: K
authors.initials: K
authors.lastname: Talks
authors.forename: R
authors.initials: R
authors.lastname: Leek
authors.forename: H
authors.initials: H
authors.lastname: Turley
authors.forename: F
authors.initials: F
authors.lastname: Pezzella
authors.forename: A
authors.initials: A
authors.lastname: Harris
authors.forename: K
authors.initials: K
authors.lastname: Gatter
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008222:Lymphokines / Q000096:biosynthesis; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000096:biosynthesis; D013939:Thymidine Phosphorylase / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D043925:Angiogenesis Inducing Agents; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D013939:Thymidine Phosphorylase; D015534:Trans-Activators; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C089226:CA9 protein, human