Study On The Mechanism And Clinical Significance Of SFRP1 And SFRP2-antagonists Of Wnt Singaling Pathway In Renal Cell Carcinoma

Objective:The study was designed to investigate the expression of Secreted Frizzled Related Protein-1(SFRP1) and Secreted Frizzled Related Protein-2(SFRP2)-antagonists of Wnt singaling pathway in renal cell carcinoma,and to determine the mechanism underlying the aberrance of the expression and its clinical significance.Method:The clincopathological characteristic of 55 patients with renal cell carcinoma from department of urology of Nanjing General Hospital between January 2009 and June 2010 after radical nephrectomy were analyzed retrospectively, according to preoperative imaging data, intraoperative condition and postoperative pathological report.The histological diagnosis of the tumors was made by two experienced pathologists based on 2004 WHO classification of renal cell carcinoma and 2010 AJCC staging criteria for pathological stage, and according to three classification of tumor cell grade.15 normal renal tissues were collected about 5cm away from the tumor as control. All specimens were confirmed renal cell carcinoma and normal kidney tissue by H-E staining. Review the pathology material of all cases again,55cases and 15 normal renal tissues were investigated by Immunohistochemical En Vision two-step staining with SFRP1,SFRP2 andβ-catenin. SPSS 16.0 software was used for statistical analysis of the association between its protein expression level and RCC histological subtype, pathologic stage,tumor cell grade, gender, age, clinical manifestations and tumor size, as well as the correlation of SFRP1, SFRP2 andβ-catenin protein expression in RCC.Results:In 55 cases with RCC, SFRP1 was positively stained in 14 cases(14/55). According to WHO histological subtype classification,9 cases were in CCRCC,3 cases were in PRCC,2 cases were in ChRCC. According to Pathological TNM stage,10 cases were in StageⅠ,3 cases were in StageⅡ,1 cases were in StageⅢ, no-expression was in StageIV. According to tumor cell grade,12 cases were in G1,2 cases were in G2, no- expression was in G3.The decreased expression of SFRP1 is correlated with the Pathological TNM stage and tumor cell grade(P<0.05). However, there is no-related with the age, sex, tumor size, histological types and Clinical symptoms (P>0.05). In 55 cases with RCC, SFRP2 was positively stained in 15 cases (15/55). According to WHO histological subtype classification,8 cases were in CCRCC,3 cases were in PRCC,4 cases were in ChRCC. According to Pathological TNM stage,11 cases were in StageⅠ,3 cases were in Stage II,1 cases were in StageⅢ, no- expression was in StageⅣ. According to tumor cell grade,13 cases were in G1, 2 cases were in G2, no- expression was in G3. The decreased expression of SFRP2 is correlated with the Pathological TNM stage and tumor cell grade(P<0.05). However, there is no- related with the age, sex, tumor size, histological types and Clinical symptoms (P>0.05). In 55 cases with RCC, aberrantβ-catenin expression was in 44 cases (44/55). According to WHO histological subtype classification,29 cases were in CCRCC,8 cases were in PRCC,7 cases were in ChRCC. According to Pathological TNM stage,14 cases were in StageⅠ,8 cases were in StageⅡ,15 cases were in StageⅢ,7 cases were in StageⅣ. According to tumor cell grade,18 cases were in G1,18 cases were in G2,8 cases were in G3. The aberrantβ-catenin expression is correlated with the Pathological TNM stage and tumor cell grade(P<0.05). However, there is no-related with the age, sex, tumor size, histological types and Clinical symptoms (P>0.05).7 cases of IV pathological stage and 8 cases of tumor cell poorly differentiated were aberrantβ-catenin expression and the lost expression of SFRP1 and SFRP2. In 15 normal renal tissues, positive expression of SFRP1 and SFRP2 protein can be tested in 13 (13/15) and 14 (14/15) samples respectively. Normalβ-catenin membrane expression can be found in 15 normal renal tissues. The difference between tumor and normal tissue is significant (P<0.05). In renal cell carcinoma, aberrantβ-catenin staining asscociated with both SFRP1 and SFRP2 expression by statistical analysis. SFRP1 negative expression and abnormal P-catenin protein expression was positively correlated (r=0.543, P<0.001), SFRP2 negative expression and abnormalβ-catenin protein expression was positively correlated (r=0.465, P<0.001). At the same time in renal cell carcinoma, SFRP1 expression asscociated with SFRP2, SFRP1 and SFRP2 expression was positively correlated (r=0.392, P=0.003).Conclusion:1. In normal kidney tissue, SFRP1 protein mainly expression in renal tubular epithelial cells, SFRP2 protein mainly expressed in glomerular endothelial cells and tubulointerstitial endothelial cells,β-catenin protein mainly expressed in renal tubular epithelial cell membrane.2. In renal cell carcinoma, SFRP1 and SFRP2 were downregulated or weakened, while P-catenin appears missing of the membrane or ectopic expression.3. In renal cell carcinoma, the downregulation or reduced expression of SFRP1 and SFRP2 was correlated with aberrant expression ofβ-catenin.4. The downregulation or reduced expression of SFRP1 and SFRP2 is correlated with Pathological TNM stage. However, there is no-related with the histological types.