title: GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression.
abstract: The goal of the present work was to evaluate the correlation of glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX) with the monocarboxylate transporters 1 (MCT1) and 4 (MCT4) and their chaperone, CD147, in breast cancer. The clinico-pathological value of GLUT1 and CAIX was also evaluated. For that, we analysed the immunohistochemical expression of GLUT1 and CAIX, in a large series of invasive breast carcinoma samples (n=124), previously characterized for MCT1, MCT4 and CD147 expression. GLUT1 expression was found in 46% of the cases (57/124), while CAIX was found in 18% of the cases (22/122). Importantly, both MCT1 and CD147, but not MCT4, were associated with GLUT1 and CAIX expression. Also, GLUT1 and CAIX correlated with each other. Concerning the clinico-pathological values, GLUT1 was associated with high grade tumours, basal-like subtype, absence of progesterone receptor, presence of vimentin and high proliferative index as measured by Ki-67. Additionally, CAIX was associated with large tumour size, high histological grade, basal-like subtype, absence of estrogen and progesterone receptors and presence of basal cytokeratins and vimentin expression. Finally, patients with CAIX positive tumours had a significantly shorter disease-free survival. The association between MCT1 and both GLUT1 and CAIX may result from hypoxia-mediated metabolic adaptations, which confer a glycolytic, acid-resistant and more aggressive phenotype to cancer cells.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Pinheiro
authors.forename: B
authors.initials: B
authors.lastname: Sousa
authors.forename: A
authors.initials: A
authors.lastname: Albergaria
authors.forename: J
authors.initials: J
authors.lastname: Paredes
authors.forename: R
authors.initials: R
authors.lastname: Dufloth
authors.forename: D
authors.initials: D
authors.lastname: Vieira
authors.forename: F
authors.initials: F
authors.lastname: Schmitt
authors.forename: F
authors.initials: F
authors.lastname: Baltazar
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis / Q000235:genetics*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D046888:Tissue Array Analysis; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D051272:Glucose Transporter Type 1; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C495677:SLC2A1 protein, human; C089226:CA9 protein, human