Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPGRANJA, S. C.LONGATTO-FILHO, A.CAMPOS, P. B. DeOLIVEIRA, C. P.STEFANO, J. T.MARTINS-FILHO, S. N.CHAGAS, A. L.HERMAN, P.D'ALBUQUERQUE, L. C.ALVARES-DA-SILVA, M. ReisCARRILHO, F. J.BALTAZAR, F.ALVES, V. A. F.2024-03-132024-03-132022PATHOBIOLOGY, v.89, n.3, p.157-165, 20221015-2008https://observatorio.fm.usp.br/handle/OPI/58624Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.engrestrictedAccessHepatocellular carcinomaMonocarboxylate transportersNon-alcoholic fatty liver diseaseWarburg effectbiomarkerscarcinoma, hepatocellularglucose transporter type 1humansliverliver cirrhosisliver neoplasmsnon-alcoholic fatty liver diseasecarbonate dehydratase ixcd147 antigenchaperoneglucose transporter 1monocarboxylate transporter 1monocarboxylate transporter 2monocarboxylate transporter 4biological markerglucose transporter 1adultadvanced canceragedarticleblood biochemistrybody masscancer patientcancer stagingcancer survivalcancer tissuecell metabolismclinical articleclinical featurecohort analysiscontrolled studydemographydiabetes mellitusdisease associationdyslipidemiaenzyme activityfemalehepatocellular carcinoma cell linehistopathologyhumanhuman cellhuman tissuehypertensionimmunohistochemistryimmunoreactivityliver cell carcinomaliver cirrhosisliver fibrosisliver noduleliver transplantationmalemetabolic parametersnecroinflammationnonalcoholic fatty livernonalcoholic steatohepatitisoverall survivalphenotypeprotein expressionretrospective studyrisk factorwarburg effectcomplicationliverliver cell carcinomaliver tumornonalcoholic fatty liverpathologyarticleCopyright S. KARGER AG10.1159/000521034