The Correlation Between VEGF-C/VEGFR-3 Expressions And Lymph Node Metastasis Of Renal Cell Carcinoma

Objective:The objective of this study was to examine the expression of vascular endothelial growth factor-C(VEGF-C)and its receptor-3(Vascular Endothelium Growth Factor Receptor-3,VEGFR-3)in renal cell carcinoma(RCC)tissues,and to investigate the possible effect of VEGF-C/VEGFR-3 on lymph node metastasis in RCC tissues.Methods:From August 2012 to December 2013,a total of 45 patients who diagnosed as RCC in our hospital were enrolled in this study,including 25 males and 20 females with an age range of 25-66 years and an average age of 53.35±8.36.All patients were underwent medical imageology examines preoperatively,including type-B ultrasonic and CT,and performed radical nephrectomy.The pathological examines showed positive RCC of 45 patients postoperatively,including 1 chromogenic cell carcinoma,2 papillary adenocarcinomas and 42 renal clear cell carcinomas.Furthermore,pathological results showed 14 cases with Lymph node metastasis,while 31 subjects without Lymph node metastasis.Normal kidney tissues were randomly collected from 10 patients at the location more than 5 cm from the edge of the kidney tumor.Both RCC and normal kidney tissues were divided into two sections,one stored at-80 for mRNA levels examine,another fixed ?in 4% paraformaldehyde for immunohistochemistry(IHC),respectively.PCR was used to examine the VEGF-C mRNA level differences between the normal and RCC tissues,and between the tissues with and without lymph node metastasis.IHC was used to investigate the immunolocalization of VEGF-C/VEGFR-3 in the normal and RCC tissues,lymphatic vessel density(LVD)was also calculated in this study.SPSS statistical software(version 20.0)was used for statistical analysis.The rank sum test and the chi-square analysis were used to analysis enumeration data,and t test analyzed measurement data between two groups,respectively.The important findings in our study include the following points.Results:1.VEGF-C mRNA level expressions PCR results showed that the VEGF-C mRNA levels in RCC tissues were significantly higher than normal kidney tissues(0.556±0.181 and 0.252±0.114,respectively)(P=0.001),and higher clinical stages(?and ?)significantly higher than lower clinical stages(and ? ?)(0.724±0.163 and 0.527±0.187,respectively)(P=0.003).Moreover,significant differences of VEGF-C expressions were also existed between the RCC tissues with and without lymph node metastasis(0.683±0.164 and 0.542±0.191,respectively,P<0.01).However,no significant correlation was observed between VEGF-C expressions and age,gender and pathological grading(P>0.05).2.VEGF-C immunolocalization and expressions in normal kidney and RCC tissues IHC results showed that the VEGF-C positive cell rate in RCC tissues was significantly higher than normal kidney tissues(85% and 30%,respectively)(P<0.01),and lymphatic metastasis positive and higher clinical stage tissues significantly greater than lymphatic metastasis negative and lower clinical stage groups,respectively(P<0.01 and P<0.05,respectively).However,no significant correlation was observed between VEGF-C immunoexpression and age,gender and pathological grading(P>0.05).3.VEGFR-3 immunolocalization and expressions in normal kidney and RCC tissues IHC results showed that VEGFR-3 was immunolocalized at cytoplasm and membrane of lymphatic endothelial cells.No significant difference of LVD was observed between the RCC and normal kidney tissues(9.84±2.68 and 10.38±2.96,respectively)(P>0.05).However,the LVD of lymphatic metastasis positive and higher clinical stage tissues(12.05±2.18 and 11.69±2037,respectively)was significantly greater than lymphatic metastasis negative and lower clinical stage tissues(8.86±2.05 and 8.85±2024,respectively),respectively(P<0.01).Conclusion:In conclusion,VEGF-C mRNA level expressions at RCC tissues were significantly greater than normal kidney tissues(P=0.001),and significant differences were also observed between the lymphatic metastasis positive and negative tissues with respect to VEGF-C mRNA expressions(P<0.01).VEGF-C immunoexpressions at normal kidney and lymphatic metastasis negative tissues were significantly lower than RCC and lymphatic metastasis positive tissues(P=0.01),respectively.Moreover,the LVD of lymphatic metastasis positive tissues was significantly larger than negative tissues(P<0.01),inferring the RCC formation and lymphatic metastasis are associated with the higher expression of VEGF-C/VEGFR-3.