Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma： Possible role in tumor promotion and angiogenesis

AIM:Toinvestigatetheassociationofcyclooxygenase-2(COX-2)expressionwithangiogenesisandthenumberandtypeofinflammatorycells(macrophages/Kupffercells;mastcells)withinprimaryhepatocellularcarcinoma(HCC)tissuesandadjacentnon-tumorous(MT)tissues.METHODS:ImmunohistochemistryforCOX-2,CD34,CD68andmastcelltryptase(MCT)wasperformedon14well-characterizedseriesofliver-cirrhosis-associatedHCCpatients.COX-2expressionandthenumberofinflammatorycellsintumorlesionsandsurroundinglivertissuesofeachspecimenwerecompared.Moreover,COX-2,CD34stainingandthenumberofinflammatorycellsinareaswithdifferenthistologicaldegreeswithineachtumorsamplewerecomparativelyanalyzed.RESULTS:ThepercentageofCOX-2positivecellswassignificantlyhigherinNTtissuesthanintumors.COX-2expressionwashigherinwell-differentiatedHCCthaninpoorly-differentiatedtissues.Fewmastcellswereobservedwithinthetumormass,whereasahighernumberwasobservedinthesurroundingtissue,especiallyinperi-portalspacesofNTtissues.Abundantmacrophages/KupffercellswereobservedinNTtissues,whereasthenumberofcellswassignificantlylowerinthetumormass.However,ahighercellnumberwasobservedinthewell-differentiatedtumorandprogressivelydecreasedinrelationtothedifferentiationgrade.Withinthetumor,apositivecorrelationwasfoundbetweenCOX-2expressionandthenumberofmacrophages/Kupffercellsandmastcells.Moreover,therewasapositivecorrelationbetweenCD34andCOX-2expressionintumortissues.Comparisonbetweenwell-andpoorly-differentiatedHCCshowedthatthenumberofCD34-positivecellsdecreasedwithdedifferentiation.However,COX-2wastheonlyindependentvariableshowingapositivecorrelationwithCD34inamultivariateanalysis.CONCLUSION:ThepresenceofinflammatorycellsandCOX-2expressioninlivertumorsuggestsapossiblerelationshipwithtumorangiogenesis.COX-2expressingcellsandthenumberofmacro