GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression
Céline Pinheiro1,2, Bárbara Sousa3, André Albergaria1,3, Joana Paredes3, Rozany Dufloth4, Daniella Vieira5, Fernando Schmitt3,6 and Fátima Baltazar1,2
1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, 2ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal, 3IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal, 4Hospital e Maternidade Celso Pierro da Pontifícia Universidade Católica de Campinas, Campinas/São Paulo, Brazil, 5Federal University of Santa Catarina UFSC Florianópolis (SC), Brazil and 6Medical Faculty of the University of Porto, Porto, Portugal.
Offprint requests to: Fátima Baltazar, Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal. e-mail: firstname.lastname@example.org
Summary. 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 clinicopathological 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. Histol Histopathol 26, 1279-1286 (2011)
Key words: GLUT1, CAIX, Monocarboxylate transporters (MCTs), CD147/EMMPRIN, Breast carcinoma, Immunohistochemistry