Expression Of PD-L1 And VEGFR-2 Proteins In Primary Site Of Synchronous Metastatic Renal Cell Carcinoma And Its Relationship With Prognosis Of Targeted Therapy

ObjectiveTo investigate the expression of Programmed Death Protein-Ligand 1(PD-L1)and Vascular Endothelial Growth Factor Receptor 2(VEGFR-2)in primary site of synchronous metastatic renal cell carcinoma,and evaluate the correlation between the expression and the clinicopathological characteristics,as well as the prognosis of targeted therapy in these patients in order to provide theoretical basis for further exploration of targeted drugs and immunological checkpoint inhibitors in the treatment of advanced renal cell carcinoma.MethodsClinicopathological data of 96 patients with synchronous metastatic renal cell carcinoma treated with cytoreductive nephrectomy from January 2006 to January 2013 were studied retrospectively from National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences.The expression of PD-L1 and VEGFR-2 proteins in 96 cases of synchronous metastatic renal cell carcinoma was detected by immunohistochemical method,and the expression level was evaluated according to the degree of cell staining.All patients received targeted drug therapy(sunitinib or soranib).The experimental data were analyzed by spss19.0 software.Chi-square test and Fisher's exact probability method Fisher exact test were used to compare the expression of PD-L1 and VEGFR-2 with clinicopathological factors and the therapeutic efficacy of targeted therapy.Survival analysis was estimated with Kaplan-Meier method,and log-rank test for difference analysis.Results1.96 patients with synchronous metastatic renal cell carcinoma received cytoreductive nephrectomy and combined with targeted therapy.The median survival time was 24.0 months(95%confidence interval 22.7-25.3 months),and the 5-year survival rate was 13.5%.2.PD-L1 protein was positive in 38 cases(39.6%)and VEGFR-2 protein was positive in 56 cases(58.3%)in 96 cases of synchronous metastatic renal cell carcinoma3.The results of single factor analysis showed that the expression of PD-L1 in the primary tumor tissues of the patients with synchronous metastatic renal cell carcinoma was not related to age,sex,KPS score,paraneoplastic syndrome,tumor diameter,LDH,blood calcium level,number of metastatic organs,pathological types(P>0.05),but related to Fuhrman classification and regional lymph node metastasis.The positive rate of PD-L1 expression in the poorly differentiated group(51.6%,33/64)was significantly higher than that in the well-differentiated group(15.6%,5/32)[x2=11.521,P=0.001],and in the regional lymph node metastasis group(57.1%,20/35)was also higher than that in non-lymph node metastasis group(29.5%,18/61)[?2=7.102,P=0.008].4.The expression of VEGFR-2 in the primary tumor tissues of the patients with synchronous metastatic renal cell carcinoma was not related to age,sex,KPS score,paraneoplastic syndrome,tumor diameter,LDH,blood calcium level,number of metastatic organs,pathological types(P>0.05),but linked with Fuhrman classification and regional lymph node metastasis.The positive rate of VEGFR-2 expression in the poorly differentiated group(65.6%,42/64)was apparently higher than that in the well-differentiated group(46.7%,14/32)[?2=4.200,P=0,04],and in the regional lymph node metastasis group(77.1%,27/35)was also higher than that in non-lymph node metastasis group(29.5%,29/61)[?2=8.018,P=0.005].5.The overall survival time of patients with positive expression of PD-L1 in the primary tumor tissues of synchronous metastatic renal cell carcinoma was markedly shorter than that of patients with negative expression(17 months,95%CI:15.7 months-18.3 months VS 27 months,95%CI:25.6 months-28.3 months)[?2=44.919,P=0.000],while the overall survival time of patients with positive expression of VEGFR-2 was significantly longer than that of patients with negative expression of VEGFR-2(25 months,95%CI:22.6 months-27.4 months VS 21 months,95%CI:18.3 months-23.6 months)[?2=5.620,P=0.018].6.Negative PD-L1 and positive VEGFR-2 expression in the primary tumor tissues of the patients with synchronous metastatic renal cell carcinoma achieved longer overall survival time than that positive PD-L1 and negative VEGFR-2 expression patients(17 months,95%:15.4 months-18.6months VS 30 months,95%CI:21.6 months-38.4 months)[?2=56.781,P=0.000].ConclusionsBoth PD-L1 and VEGFR-2 protein were expressed in the primary tumor tissues of the patients with synchronous metastatic renal cell carcinoma.The positive expression of PD-L1 and the negative expression of VEGFR-2 may be related to the poor therapeutic effect of targeted therapy of renal cell carcinoma,which needs to be confirmed by large clinical studies.