Study On The Expression And Relationship Of Endostatin, VEGF, BFGF And MVD In Renal Cell Carcinoma

Objective Renal cell carcinoma(RCC)is one of the most common malignant tumor in urinary system,accounts for about 3%of all human cancers,second only bladder carcinoma.Its incidence and mortality have continuously increased during the last 50 years.The tumor which accounts for about 45%of total have metastasized when patients first visit,and the percent 50 of cases relapse after operation.Five-year survival rates for RCC,although gradually improving,remain around 50～60% because of the high resistance of metastatic disease to traditional therapy including radi-and chemotherapy.A large amount of research has been done to explore new prognostic indicators for RCC,molecular immunotherapy,gene therapy and anti-neovascularization molecular targeted therapy are effective for advanced stage or metastatic RCC.However,numerous biomolecular factors are currently under investigation to determine their usefulness and correlation with diagnosis,stage and prognosis for RCC.These molecular markers include measures of tumor cell proliferation,growth factors,cell adhesion,apoptosis,telornerase activity and angiogenesis.Angiogenesis,the formation of new blood vessels out of pre-existing capillaries,plays a key role in the growth and metastasis of solid tumors.Renal cell carcinoma is a highly angiogenic tumor known to secrete vascular endothelial cell growth factor(VEGF).Endostatin is an endogenous antiangiogenic agent with antitumor activity in mice.This study was designed to investigate the involvement of angiogenesis and vascular control factors including endostatin,VEGF,bFGF and MVD in the pathogenesis of renal cell carcinoma and to provide some valuable criteria for biotherapy in renal cell carcinoma.Materials and methods A total of 50 consecutive patients from department of urology,second hospital of Tianjin medical university,Tianjin institute of urology (26 males and 24 females)with RCC undergoing nephrectomy and information complete,with accession from January 2005 through October 2007,were included in this study.The median age was 55 years with a range of 30～78 years.WHO grade:Ⅰgrade was in 15 cases,Ⅱgrade was in 24 cases,Ⅲgrade was in 11 cases.Robson clinical stage:Ⅰstage was in 14 cases,Ⅱstage was in 21 cases,Ⅲstage was in 10 cases,Ⅳstage was in 5 cases.Thirty normal tissue of＞2cm domain beside tumor were recruited as normal controls.Tissue from 50 cases of RCC by immunohistochemical staining was assessed without knowledge of the patient's clinicopathological characteristics by two senior pathology doctor through double blind method.The expression of endostatin,VEGF and bFGF is amber-coloured particle in cytoplasm.The score criteria apply method of liang zhong Xu.Areas of highest neovascularization with in the stained sections from each tumor were identified under low power light microscopy(×100)and detailedly studied under high power field(×200).The value of MVD per HPF was obtained by counting ten consecutive HPFs.Sizes of primary tumor were obtained from postoperative pathological reports.The relationship between endostatin,VEGF,bFGF and MVD, and tumor grade was determined.SPSS 13.0 software application was used for all analysis and statistical significance was defined as P values less than 0.05.Results(1)The expression ratios of endostatin in normal kidney tissue and in renal cell carcinoma were 36.7%and 76%respectively,showing significant difference (x~2=14.892,P＜0.01).The endostatin expression in 50 cases of carcinoma was associated with clinical stages(P＜0.05),while no significant difference was detected in sex,age,the size of tumor and histologic grade.(2)The expression ratios of VEGF in normal kidney tissue and in renal cell carcinoma were 20%and 74%respectively, showing significant difference(x~2=23.636,P＜0.01).The VEGF expression in 50 cases of carcinoma was associated with clinical stages(P＜0.05),while no significant difference was detected in sex,age,the size of tumor and histologic grade.(3)The expression ratios Of bFGF in normal kidney tissue and in renal cell carcinoma were 23.3%and 68%respectively,showing significant difference(x~2=16.426,P＜0.01). The bFGF expression in 50 cases of carcinoma was associated with clinical stages(P＜0.05),while no significant difference was detected in sex,age,the size of tumor and histologic grade.(4)The mean MVD in renal cell carcinoma and in normal tissue was(35.62±11.38)and(18.71±9.53)respectively,showing significant difference (t=6.824,P＜0.01).In 50 cases of carcinoma,the mean MVD in stageⅢ～Ⅳ(41.29±10.65)was much higher than in stageⅠ～Ⅱ(24.74±7.83)(P＜0.01),but had no significant difference in sex,age,size of tumor and histologic grade.(5)There were statistically significant correlation between endostatin and MVD,VEGF and MVD,bFGF and MVD,endostatin,VEGF and bFGF.Conclusion(1)The experiment suggests that endostatin,VEGF,bFGF and MVD play roles in oncogenesis and progression of renal cell carcinoma.(2)The high positive expression of endostatin,VEGF,bFGF was associated with high clinical stages(P＜0.05).(3)The high positive expression of MVD was associated with high clinical stages and grade(P＜0.05).(4)There is a significantly correlation between abundant endostatin,VEGF,bFGF and MVD in renal cell carcinoma.Angiogenic growth factors and angiogenesis inhibitor play an important role in the neoangiogenesis of renal cell carcinoma.(5)Endostatin,VEGF and bFGF may be important targets for antiangiogenesis therapy in patients with renal cell carcinoma.