Tumor VEGF expression correlates with tumor stage and identifies prognostically different groups in patients with clear cell renal cell carcinoma

Objectives: Vascular endothelialgrowthfactor(VEGF)isapotentinduceroftumorangiogenesisandrepresentsthekeyelementinthepathogenesis ofclearcellrenalcellcarcinoma(ccRCC).TheaimofthisstudywastoinvestigatetheuseoftumorVEGFexpressionasaparameter toidentifytumorstageandprognosticallydifferentpatientgroups.Methods andmaterials: We retrospectivelycollectedclinicaldataof137patientstreatedwithpartialorradicalnephrectomyatourinstitutions fororgan-confined, locallyadvanced,andmetastaticccRCCsbetween1984and2013.TumorcellVEGFimmunohistochemicalexpression wascomparedwithpathologicalandclinicalfeaturesincludingage,sex,tumorstage,andFuhrmangrade.ComparisonofVEGFexpression levelsbetweentumorstageswasperformedviaKruskal-Wallisnonparametrictest.SurvivalanalysiswasconductedviaKaplan-Meier product-limitmethod,andMantel-Haenszellog-ranktestwasemployedtocomparesurvivalamonggroups.Results: Medianageatdiagnosiswas61years(range:33–85y).TumorstagewaspT1N0M0in67patients(49%),pT2N0M0in5(4%),andpT3N0M0in25(18%),while40patients(29%)hadmetastatictumorsat diagnosis.FuhrmannucleargradewasG1in22patients(16%),G2in60(44%),G3in33(24%),G4in13patients(9%),andunknownin9patients. TumorVEGFwasdifferentiallyexpressedamongdifferentstages(P o 0.001)andinlow(G1–2)andhigh(G3–4) Fuhrmangradetumors(P o 0.001).Nosignificantdifferenceswerefoundwhenstratifyingbysex(P ¼ 0.06)orage(P ¼ 0.29).Medianoverallsurvival(OS)frompartialorradicalnephrectomywas161months(range:1–366).Weobservedasignificantly longerOSinpatientswithlow(o25%)vs.high(425%)VEGFexpressionlevels(medianOS206vs.65mo, P o 0.001).Conclusions: OurdatashowthattumorcellVEGFexpressionissignificantly associatedwithtumorstageandFuhrmangradeandisable topredictpatientoutcome,suggestingapotentialuseofthisparameter inidentifyingprognosticallydifferentpatientswithccRCC.