Significance of stromal-1 and stromal-2 signatures and biologic prognostic model in diffuse large B-cell lymphoma

(整期优先)网络出版时间:2017-02-12
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Objective:DiffuseLargeBCellLymphoma(DLBCL)isaheterogeneousgroupoftumorswithdifferentbiologicalandclinicalcharacteristicsthathaveperseclinicaloutcomesandresponsetotherapy.Stromal-1signatureoftumormicroenvironmentofDLBCLrepresentsextracellularmatrixdepositionandhistiocyticinfiltrate,whereasstromal-2representsangiogenesisthatcouldaffecttumorprogression.Methods:Theaimofthepresentstudyistoassessthesignificanceofstromal-1signatureusingSPARC-1andstromal-2signatureusingCD31expressionandthenfinallytoconstructbiologicprognosticmodel(BPM)in60casesofDLBCLviaimmunohistochemistry.Results:Microvesseldensity(P<0.05)andSPARCpercentageofexpression(P<0.001)werehigherinDLBCL,includinggerminalandnongerminalcases,comparedwithreactivefollicularhyperplasia.Highmicrovesseldensitywassignificantlyassociatedwithsplenicinvolvement(P=0.008),highmitoticcount(P=0.045),andpresenceofcapsularinvasion(P=0.035).PercentageofSPARCexpressionwassignificantlyassociatedwithsplenicinvolvement(P=0.03).ConstructingBPMshowedthat42cases(70%)wereoflowbiologicscore(0–1)and18cases(30%)wereofhighbiologicscore(2–3).LowBPMcasesshowedlessprobabilityforsplenicinvolvement(P=0.04)andahigherrateofcompleteresponsetotherapycomparedwithhighscorecases(P=0.08).Conclusions:TheDLBCLmicroenvironmentcouldmodulatetumorprogressionbehaviorsinceangiogenesisandSPARCpositivestromalcellspromotedisseminationbyassociationwithspleeninvolvementandcapsularinvasion.Biologicprognosticmodels,includingmodifiedBPM,whichconsideredcelloriginofDLBCLandstromalsignaturepathways,coulddetermineDLBCLprogressionandresponsetotherapy.