title: Angiogenin is up-regulated in the nucleus and cytoplasm in human primary breast carcinoma and is associated with markers of hypoxia but not survival.
abstract: Angiogenin, a 14.2 kD polypeptide that was originally noted for its angiogenic activity, is now increasingly recognized to have a multiplicity of biological roles in both physiological and pathological conditions. In breast cancer, there are conflicting studies questioning the role of angiogenin. Here, the pattern of expression of angiogenin during the transition from normal breast tissue to ductal carcinoma in situ and invasive carcinoma is reported together with the correlates between the level of angiogenin in 239 invasive carcinomas and standard clinicopathological parameters, hypoxia-inducible factor (HIF)-1 alpha and the HIF-1 alpha target gene DEC-1. This study shows that angiogenin expression is up-regulated in the cytoplasmic and nuclear compartments in in situ carcinoma and invasive carcinoma compared with normal breast tissue and that angiogenin expression in invasive carcinomas is significantly positively associated with high tumour grade (p = 0.03), positive oestrogen receptor (ER) status (p = 0.01), HIF-1 alpha (p = 0.001) and DEC 1 (p = 0.001), but not with patient age (p = 0.8), tumour size (p = 0.25), lymph node status (p = 0.69), epidermal growth factor receptor (p = 0.56) or microvessel density (p = 0.32). No difference in relapse-free (p = 0.26) or overall (p = 0.63) survival was observed in patients stratified by angiogenin expression. This study suggests that angiogenin may be important in breast cancer progression and that, through its relationship with ER, it may be a target for tamoxifen.
authors.affiliation: Nuffield Department Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Leticia
authors.initials: L
authors.lastname: Campo
authors.forename: Helen
authors.initials: H
authors.lastname: Turley
authors.forename: Cheng
authors.initials: C
authors.lastname: Han
authors.forename: Francesco
authors.initials: F
authors.lastname: Pezzella
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Gatter
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; C046366:angiogenin; D012259:Ribonuclease, Pancreatic