Significance Of COX-2 And VEGF-C Expression In Urothelial Carcinoma Of Upper Urinary Tract

Objectivs: To assess the expression pattern of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor C (VEGF-C) in human upper urinary tract urothelial carcinoma(UUTUC) , and to evaluate their clinical significance.Methods: Our study comprised samples from 43 patients (median age at 65years, range 37-81)with UUTUC who underwent nephroureterectomy at Fujian Provincial Hospital between January 2002 and June 2009. All specimens were pathologically confirmed. Patients included 32men and 11women, 28 were renal pelvis carcinoma, 15 were ureteral carcinoma. 12 upper urinary tract normal urothelial epithelium specimens which also pathologically confirmed were taken as control group. 5 from the renal pelvis after nephrectomy because of renal trauma, 7 from the ureter after nephroureterectomy because of renal cell carcinoma(RCC). According to the TNM classification system and WHO(1998)grading system, they were: 1 case of 0 stage, 14 cases of I stage, 5 cases of II stage, 14 cases of III stage, 9 cases of IV stage; 15 cases of G1, 19 cases of G2, 9 cases of G3. Lymph node metastasis was found in 6 samples.Two-steps immunohistochemistry was applied to detect the expression pattern of COX-2 and VEGF-C in 43 UUTUC tissues and 12 normal upper urinary tract(UUT) tissues. The possible relationship of COX-2 and VEGF-C immunoreactivity with tumor grade,stage,lymph node metastasis was evaluated.Results:1. The expression of COX-2 was mainly distributed in tumor cell cytoplasm, positive expressions were found in 76.7% patients with UUTUC, the positive expression rates in UUTUC were significantly higher than that in 12 normal UUT tissues (P<0.01). COX-2 immunoreactivity in tumor cells correlated with tumor grade and stage (P<0.05), while the correlation was not found with gender and age and sites(renal pelvis or ureter). There was no significant correlation between expression level of COX-2 and lymph node metastasis (P=0.09).2. The expression of VEGF-C was mainly distributed in tumor cell cytoplasm, positive expressions were found in 67.4% patients with UUTUC, the positive expression rates in UUTUC were significantly higher than that in 12 normal UUT tissues (P<0.01). VEGF-C immunoreactivity in tumor cells correlated with tumor grade and stage (P<0.05), while the correlation was not found with gender and age and sites(renal pelvis or ureter). The expression level of VEGF-C correlated with lymph node metastasis(P=0.011).3. There was positive correlation between VEGF-C expression with COX-2 expression in UUTUC tissues (r=0.675,P<0.01).Conclusions: 1. Both the expression of COX-2 and VEGF-C were positive in UUTUC, and the positive expression rates were higher than that in normal tissues. 2. Both COX-2 and VEGF-C expressions are related to the grade and stage of UUTUC. 3. There is correlation between VEGF-C expression and lymph node metastasis of UUTUC. The co-expression pattern of COX-2 and VEGF-C in UUTUC suggest that they may act synergistically in development and progression of UUTUC.