Research Report
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2014; 20(33): 11780-11787
Published online Sep 7, 2014. doi: 10.3748/wjg.v20.i33.11780
Characterization of monocarboxylate transporter activity in hepatocellular carcinoma
Venâncio A Alves, Céline Pinheiro, Filipa Morais-Santos, Aloisio Felipe-Silva, Adhemar Longatto-Filho, Fátima Baltazar
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
Céline Pinheiro, Filipa Morais-Santos, Adhemar Longatto-Filho, Fátima Baltazar, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4704-553 Braga, Portugal
Céline Pinheiro, Filipa Morais-Santos, Adhemar Longatto-Filho, Fátima Baltazar, ICVS/3B’s-PT Government Associate Laboratory, 4710-057 Braga/ Guimarães, Portugal
Céline Pinheiro, Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, Barretos, São Paulo, SP 13083-970, Brazil
Céline Pinheiro, Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Sao Paulo, 14780-000, Brazil
Adhemar Longatto-Filho, Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, Barretos 14780-000, Brazil
Author contributions: All the authors contributed to this manuscript.
Correspondence to: Venâncio A Alves, MD, PhD, Professor, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, University of São Paulo School of Medicine, Brazil, Dr. Arnaldo Ave. 455 Room 1153, São Paulo, SP 1246-903, Brasil. venancio@uol.com.br
Telephone: +55-11-30617413 Fax: +55-11-30617413
Received: January 12, 2014
Revised: March 7, 2014
Accepted: June 14, 2014
Published online: September 7, 2014
Abstract

AIM: 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 χ2 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.

CONCLUSION: MCT4 and GLUT1 appear to play a role in HCC progression, while MCT2 is lost during progression and associated with better prognosis.

Keywords: Hepatocellular carcinoma, Monocarboxylate transporters, Glycolysis, Cirrhosis, Glucose transporter-1

Core tip: This paper describes, for the first time, the role of monocarboxylate transporters in hepatic carcinoma. The characterization of monocarboxylate transporter activity in acidic metabolism of primary and metastatic hepatocellular carcinoma microenvironment was studied in necropsy material and allowed us to precisely evaluate the impact of the more acidic microenvironment that is potentially maintained by monocarboxylate transporter 4 and glucose transporter-1 during hepatocellular carcinoma progression.