Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorGRANJA, S. C.
dc.contributor.authorLONGATTO-FILHO, A.
dc.contributor.authorCAMPOS, P. B. De
dc.contributor.authorOLIVEIRA, C. P.
dc.contributor.authorSTEFANO, J. T.
dc.contributor.authorMARTINS-FILHO, S. N.
dc.contributor.authorCHAGAS, A. L.
dc.contributor.authorHERMAN, P.
dc.contributor.authorD'ALBUQUERQUE, L. C.
dc.contributor.authorALVARES-DA-SILVA, M. Reis
dc.contributor.authorCARRILHO, F. J.
dc.contributor.authorBALTAZAR, F.
dc.contributor.authorALVES, V. A. F.
dc.date.accessioned2024-03-13T19:54:24Z
dc.date.available2024-03-13T19:54:24Z
dc.date.issued2022
dc.description.abstractIntroduction: 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.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.sponsorshipICVS, (PPBI-POCI-01-0145-FEDER-022122)
dc.description.sponsorshipFundação para a Ciência e a Tecnologia, FCT, (NORTE-01-0145-FEDER-000039, UIDB/50026/2020, UIDP/50026/2020)
dc.description.sponsorshipEuropean Regional Development Fund, ERDF, (SFRH/BPD/117858/2016)
dc.identifier.citationPATHOBIOLOGY, v.89, n.3, p.157-165, 2022
dc.identifier.doi10.1159/000521034
dc.identifier.issn1015-2008
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/58624
dc.language.isoeng
dc.publisherS. KARGER AGeng
dc.relation.ispartofPathobiology
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright S. KARGER AGeng
dc.subjectHepatocellular carcinomaeng
dc.subjectMonocarboxylate transporterseng
dc.subjectNon-alcoholic fatty liver diseaseeng
dc.subjectWarburg effecteng
dc.subject.otherbiomarkerseng
dc.subject.othercarcinoma, hepatocellulareng
dc.subject.otherglucose transporter type 1eng
dc.subject.otherhumanseng
dc.subject.otherlivereng
dc.subject.otherliver cirrhosiseng
dc.subject.otherliver neoplasmseng
dc.subject.othernon-alcoholic fatty liver diseaseeng
dc.subject.othercarbonate dehydratase ixeng
dc.subject.othercd147 antigeneng
dc.subject.otherchaperoneeng
dc.subject.otherglucose transporter 1eng
dc.subject.othermonocarboxylate transporter 1eng
dc.subject.othermonocarboxylate transporter 2eng
dc.subject.othermonocarboxylate transporter 4eng
dc.subject.otherbiological markereng
dc.subject.otherglucose transporter 1eng
dc.subject.otheradulteng
dc.subject.otheradvanced cancereng
dc.subject.otheragedeng
dc.subject.otherarticleeng
dc.subject.otherblood biochemistryeng
dc.subject.otherbody masseng
dc.subject.othercancer patienteng
dc.subject.othercancer stagingeng
dc.subject.othercancer survivaleng
dc.subject.othercancer tissueeng
dc.subject.othercell metabolismeng
dc.subject.otherclinical articleeng
dc.subject.otherclinical featureeng
dc.subject.othercohort analysiseng
dc.subject.othercontrolled studyeng
dc.subject.otherdemographyeng
dc.subject.otherdiabetes mellituseng
dc.subject.otherdisease associationeng
dc.subject.otherdyslipidemiaeng
dc.subject.otherenzyme activityeng
dc.subject.otherfemaleeng
dc.subject.otherhepatocellular carcinoma cell lineeng
dc.subject.otherhistopathologyeng
dc.subject.otherhumaneng
dc.subject.otherhuman celleng
dc.subject.otherhuman tissueeng
dc.subject.otherhypertensioneng
dc.subject.otherimmunohistochemistryeng
dc.subject.otherimmunoreactivityeng
dc.subject.otherliver cell carcinomaeng
dc.subject.otherliver cirrhosiseng
dc.subject.otherliver fibrosiseng
dc.subject.otherliver noduleeng
dc.subject.otherliver transplantationeng
dc.subject.othermaleeng
dc.subject.othermetabolic parameterseng
dc.subject.othernecroinflammationeng
dc.subject.othernonalcoholic fatty livereng
dc.subject.othernonalcoholic steatohepatitiseng
dc.subject.otheroverall survivaleng
dc.subject.otherphenotypeeng
dc.subject.otherprotein expressioneng
dc.subject.otherretrospective studyeng
dc.subject.otherrisk factoreng
dc.subject.otherwarburg effecteng
dc.subject.othercomplicationeng
dc.subject.otherlivereng
dc.subject.otherliver cell carcinomaeng
dc.subject.otherliver tumoreng
dc.subject.othernonalcoholic fatty livereng
dc.subject.otherpathologyeng
dc.titleNon-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolismeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryPortugal
hcfmusp.affiliation.countryisopt
hcfmusp.author.externalGRANJA, S. C.:Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal, ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal, Research Centre in Health and Environment (CISA), School of Health (ESS), Polytechnic Institute of Porto (P.PORTO), Porto, Portugal, Department of Pathological, Cytological and Thanatological Anatomy, ESS|P.PORTO, Porto, Portugal
hcfmusp.author.externalALVARES-DA-SILVA, M. Reis:Division of Gastroenterology, Hospital de Clinicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil
hcfmusp.author.externalBALTAZAR, F.:Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal, ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
hcfmusp.author.externalALVES, V. A. F.:Department of Pathology (LIM-14), University of São Paulo School of Medicine, São Paulo, Brazil
hcfmusp.citation.scopus2
hcfmusp.contributor.author-fmusphcADHEMAR LONGATTO FILHO
hcfmusp.contributor.author-fmusphcPRISCILA BRIZOLLA DE CAMPOS
hcfmusp.contributor.author-fmusphcCLAUDIA PINTO MARQUES SOUZA DE OLIVEIRA
hcfmusp.contributor.author-fmusphcJOSE TADEU STEFANO
hcfmusp.contributor.author-fmusphcSEBASTIAO NUNES MARTINS FILHO
hcfmusp.contributor.author-fmusphcALINE LOPES CHAGAS
hcfmusp.contributor.author-fmusphcPAULO HERMAN
hcfmusp.contributor.author-fmusphcLUIZ AUGUSTO CARNEIRO D ALBUQUERQUE
hcfmusp.contributor.author-fmusphcFLAIR JOSE CARRILHO
hcfmusp.description.beginpage157
hcfmusp.description.endpage165
hcfmusp.description.issue3
hcfmusp.description.volume89
hcfmusp.origemSCOPUS
hcfmusp.origem.dimensionspub.1144760120
hcfmusp.origem.pubmed35042213
hcfmusp.origem.scopus2-s2.0-85124030508
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