title: Characterization of monocarboxylate transporter activity in hepatocellular carcinoma.
abstract: OBJECTIVE
  To assess the immunoexpression of hypoxia-related markers in samples from cirrhosis and primary and metastatic hepatocellular carcinoma (HCC).
  
  
  METHODS
  From a total of 5836 autopsies performed at the Pathology Department - University of Sao Paulo School of Medicine Hospital - from 2003 to 2009, 188 presented primary liver tumors. Immunohistochemical reactivity for monocarboxylate transporters (MCTs)-1, 2 and 4, CD147 and glucose transporter-1 (GLUT1) was assessed in necropsies from 80 cases of HCC. Data were stored and analyzed using the IBM SPSS statistical software (version 19, IBM Company, Armonk, NY). All comparisons were examined for statistical significance using Pearson's χ (2) test and Fisher's exact test (when n < 5). The threshold for significant P values was established as P < 0.05.
  
  
  RESULTS
  Plasma membrane expression of MCT4 and overall expression of GLUT1 showed progressively higher expression from non-neoplastic to primary HCC and to metastases. In contrast, overall expression of MCT2 was progressively decreased from non-neoplastic to primary HCC and to metastases. MCT1 (overall and plasma membrane expression), MCT2 and CD147 plasma membrane expression were associated with absence of cirrhosis, while plasma membrane expression of CD147 was also associated with absence of HBV infection. MCT2 overall expression was associated with lower liver weight, absence of metastasis and absence of abdominal dissemination. Additionally, MCT4 plasma membrane positivity was strongly associated with Ki-67 expression.
  
  
  CONCLUSIONS
  MCT4 and GLUT1 appear to play a role in HCC progression, while MCT2 is lost during progression and associated with better prognosis.
authors.affiliation: Venâncio A Alves, Aloisio Felipe-Silva, Adhemar Longatto-Filho, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP 1246-903, Brazil.
authors.forename: Venâncio A
authors.initials: VA
authors.lastname: Alves
authors.affiliation: Venâncio A Alves, Aloisio Felipe-Silva, Adhemar Longatto-Filho, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP 1246-903, Brazil.
authors.forename: Céline
authors.initials: C
authors.lastname: Pinheiro
authors.affiliation: Venâncio A Alves, Aloisio Felipe-Silva, Adhemar Longatto-Filho, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP 1246-903, Brazil.
authors.forename: Filipa
authors.initials: F
authors.lastname: Morais-Santos
authors.affiliation: Venâncio A Alves, Aloisio Felipe-Silva, Adhemar Longatto-Filho, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP 1246-903, Brazil.
authors.forename: Aloisio
authors.initials: A
authors.lastname: Felipe-Silva
authors.affiliation: Venâncio A Alves, Aloisio Felipe-Silva, Adhemar Longatto-Filho, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP 1246-903, Brazil.
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.affiliation: Venâncio A Alves, Aloisio Felipe-Silva, Adhemar Longatto-Filho, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP 1246-903, Brazil.
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
mesh_terms: D001344:Autopsy; D051926:Basigin / Q000032:analysis; D001938:Brazil; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000556:secondary; D002462:Cell Membrane / Q000737:chemistry*; D016009:Chi-Square Distribution; D018450:Disease Progression; D051272:Glucose Transporter Type 1 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology; D027501:Monocarboxylic Acid Transporters / Q000032:analysis*; D009124:Muscle Proteins / Q000032:analysis; D011379:Prognosis; D027981:Symporters / Q000032:analysis; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D051926:Basigin; D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human; C406962:SLC16A4 protein, human; C490427:SLC16A7 protein, human; C495677:SLC2A1 protein, human
keywords: Cirrhosis; Glucose transporter-1; Glycolysis; Hepatocellular carcinoma; Monocarboxylate transporters