Expression Of Vascular Endothelial Growth Factor C(VEGF-C) And Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) In Transitional Cell Carcinoma (TCC) Of Bladder

IntroductionTumor of bladder is the most common tumor in urinary system, and it ranks the eighth place among common tumors in our country. Its 97% pathological type stems from epithelia tissue,and most of them is transitional cell carcinoma. The main metastatic mode of transitional cell carcinoma is lymphatic metastasis.In the recent years, with the recognition of reaction between vascular endo-thelia growth factor VEGF and tumorangiogenesis, some growth factors and receptors with specific effect on endothelium of lymph — vessel were found in succession , and new path is opened for studying lymphatic metastasis. VEGF - C was found by Jounov( et. al) in 1996 in cell nutrient fluid for cancer of the prostate gland, as a kind of factor that can stimulate tyrosine phosphorylating of receptor VEGFR - 3 , it was then separated and purified, and its cDNA was cloned, it was verified as a kind of new congener of VEGF,namely, VEGF - C. Its receptor VEGFR - 3 is relatively specifically expressed on endotheliocyte of lymph -vessel. Kaipainen(et. al) found that VEGF - C and its receptor VEGFR -3 is the only group of regulatory factor that regulates the formation of lymph - vessel of embryonic tissue and physiological function of lymph - vessel in mature individual that has been found up to now, thus VEGF - C is also called lymph - vessel endotheliocyte growth factor, it has merely little amount of expression in the endocrine cell and endocrine glands cell of respiratory tract and alimentary tract of normal adult. Its receptor VEGFR - 3 exists in all endotheliocytes in the primary stage of embryogeny, and it is then positioned on venule and lymph - ves-sel. It is the specific label of mature lymph - vessel endotheliocytes. It is shown in many research results that new lymph - vessel and dilated lymph — vessel a-round tumor may be seen in the tumor tissue. VEGFR - 3 presents high expression on lymph - vessel with carcinoma embolus and lymph - vessel endothelio-cyte in lymph node with tumor metastasis. The VEGFR - 3 of endotheliocyte of new blood vessel in tumor is newly expressed again. That suggests VEGF - C/ VEGFR - 3 regulatory system may regulate the formation of tumor mesenchyme vascular net and the genesis of lymph - vessel. It is found through research that the expression of VEGF - C and (or) VEGFR -3 are (is) increased in tumor cells of carcinoma of colon, cancer of the rectum, cancer of the prostate gland, gastric cancer, cancer of the esophagus, mammary cancer, and so on, the expression of VEGFR - 3 and the expression of VEGF - C present positive correlation, it presents negative correlation with the differentiation extent of tumor, and it is closely associated with the metastasis of tumor cell. VEGF — C may stimulate the proliferation of lymph - vessel, lymphatic metastasis is the main path for metastasis of transitional cell carcinoma of bladder, it is also the important factor that affects postoperative recurrence and survival. There is still little research on the expression of VEGF - C and its receptor VEGFR - 3 in transitional cell carcinoma of bladder at home and abroad, it needs further studying.Objective:To investigate to VEGF - C and VEGFR - 3 expression in bladder tumor and the significance in evaluating the stage and classification and get to know the relationship between the expression and the recurrence of bladder tumor.Method44 cases of surgically resected bladder transitional cell carcinoma sample were collected in 1998 - 2003 and 10 cases of normal bladder tissue come from transvesical prostatectomy. VEGF - C, VEGFR - 3 expression were detected by SP of immunothistochemistry. The SPSS 11.0 statistical package program wasused for all analysis.Result1,Expression of VEGF - C and its receptor VEGFR - 3 in normal bladder tissue: there is no expression of VEGF - C and its receptor VEGFR - 3 in 10 cases of normal bladder tissue.2,Expression of VEGF - C and its receptor VEGFR -3 in transitional cell carcinoma of bladder: the positive rate of VEGF - C in 44 cases of transitional cell carcinoma tissue of bladder is 90. 9% (40/44) , the positive product is brown grain located within cytoplasm of transitional cell carcinoma of bladder. The expression of VEGF - C in well - differentiated (Gl grade) transitional cell carcinoma of bladder is mostly seen in the cells around cancer nest, the staining is relatively weak,it mostly presents diffused distribution in poorly differentiated ( G3 grade) transitional cell carcinoma, the staining is reactively stong. The positive rate of VEGFR -3 is 81. 8% (36/44) , positive product is located in cytoplasm of transitional cell carcinoma of bladder and the interstitial vassal endothe-liocyte cytoplasm. The difference between both of them and the expression in normal bladder tissue has significant sense (both P =0.000)3,The relation between expression of VEGF - C and its receptor VEGFR -3 and clinical pathological feature of transitional cell carcinoma of bladder: it is shown through statistical analysis that the expression of VEGFR - 3 in transitional cell carcinoma of bladder presents positive correlation (r =0. 9899, P =0. 000 ). the expression of VEGF - C and its receptor VEGFR - 3 and the degree of differentiation of transitional cell carcinoma of bladder presents negative correlation ( r = 0. 383, P = 0. 010, r = 0. 379, P = 0. 011) , the difference between expressions of VEGF - C and its receptor VEGFR - 3 in well - differentiated carcinoma ( G1 ) and poorly differentiated carcinoma ( G3) and medium differentiated carcinoma ( G2) and poorly differentiated carcinoma ( G3) has significant sense ( P =0. 031/0. 011: P =0. 010/0. 043 ) , and the difference in well - differentiated carcinoma (G1) and medium differentiated carcinoma (G2) has no significant sense (P =0. 554/0. 395). The expression of VEGF - C and its re-...