AIM:Toinvestigatetheproteinexpressionofphosphataseandtensinhomolog(PTEN)inhumanliverbiopsiesofpatientswithalcoholicandnon-alcoholicliverdisease.METHODS:PTENproteinexpressionwasassessedbyimmunohistochemistryinformalin-fixed,paraffinembeddedliversectionsofpatientswithnon-alcoholicfattyliverdisease(NAFLD)(n=44)oralcoholicliverdisease(ALD)(n=25).Liverresectionsobtainedfrom3healthysubjectscandidateforpartialliverdonationservedascontrols.Histologicalevaluationswereperformedbytwoexperiencedpathologists,anddiagnosesestablishedbasedoninternationalcriteria.TheintensityofthePTENstaininginnucleiwascomparedbetweensteatoticandnon-steatoticareasofeachliverfragmentanalyzed.Foreachliverspecimen,theantibody-stainedsectionswereexaminedandscoredblindlybythreeindependentobservers,whowereunawareofthepatients’clinicalhistory.RESULTS:Inhealthyinpiduals,PTENimmunostainingwasintenseinboththecytoplasmandnucleiofallhepatocytes.However,PTENwasstronglydownregulatedinboththenucleusandthecytoplasmofhepatocytesfromsteatoticareasinpatientswithNAFLD,independentlyofthediseasestage.Incontrast,nochangesinPTENproteinexpressionwereobservedinpatientswithALD,regardlessofthepresenceofsteatosisorthestageofthedisease.ThedegreeofPTENdownregulationinhepatocytesofpatientswithNAFLDcorrelatedwiththepercentageofsteatosis(r=0.3061,P=0.0459)andtheBMI(r=0.4268,P=0.0043).Hovewer,inpatientswithALD,PTENexpressionwasnotcorrelatedwiththepercentageofsteatosiswithorwithoutobesityasaconfoundingfactor(P=0.5574).Finally,PTENexpressionlevelinsteatoticareasofALDpatientswassignificantlydifferentfromthatseeninsteatoticareasofNAFLDpatients(P<0.0001).CONCLUSION:PTENproteinexpressionisdownregulatedearlyinNAFLD,butnotinALD.PTENimmunohistochemicaldetectioncouldhelpinthedifferentialdiagnosisofN
