The Association Of Lymphangiogenesis And Biological Behavior In Bladder Transitional Cell Carcinoma

Objective To explore the expression of vascular endothelial growth factor-D (VEGF-D) and D2-40 which is a specific antibody for lymphatic endothelial cell. Moreover to investigate the distribution characteristics of lymphatic vessels, lymphatic vessel density (LVD) and the correlation with the clinical and pathologic factors in bladder transitional cell carcinoma (BTCC). Furthermore to analyze the possible mechanism of tumor growth, progression and lymph node metastasis in BTCC.Methods SP immunohistochemical method and tissue microarray were used to detect the expression of VEGF-D and SP immunohistochemical method was used to examine the expression of D2-40 in 15 normal bladder tissues and 53 samples of BTCC. Then the LVD was counted.Results The expression of VEGF-D in all the 15 normal bladder tissues was negative. However, only 14 BTCC tissues stained negatively of all the 53 BTCC tissues. The expression level of VEGF- D in BTCC tissue group was significantly higher than that in normal bladder tissue group (P<0.01). The expression of VEGF-D was associated with tumor grade(P<0.01), clinical stage(P<0.01) and lymph node metastasis (P<0.01), but not with the age (P>0.01) and sex (P>0.01). The LVD in intra-tumor of BTCC tissues was higher than that in normal bladder tissues (P<0.01). While the LVD in peri-tumor of BTCC tissue was significantly higher than that in normal bladder tissue (P<0.01). There were many differences in vary areas of tumor. The LVD in peri-tumor of BTCC tissue was significantly higher than that in intra-tumor (P<0.01). The LVD in intra-tumor positively correlated with tumor grade(P<0.01), clinical stage(P<0.01)and lymph node metastasis (P<0.01), but not with the age(P>0.01) and sex (P>0.01), as peri-tumor. And there was positive correlation between VEGF-D and LVD (P₃<0.01 r_s3=0.833).Conclusion1. The BTTC cells were stained positively for VEGF- D. And the expression of VEGF-D was associated with tumor grade, clinical stage and lymph node metastasis. It suggests that the expression of VEGF-D plays an important role in promoting BTCC growth, progression and lymph node metastasis. It may be a marker to predict the biology behavior of BTCC.2. The lymphatic vessvels appeared in BTCC, and some of them were the new vessvels. The lymphatic vessvels mainly distributed in the peri-tumor of tumor, the shapes of which were dilated. The LVD in intra-tumor and peri-tumor positively correlated with tumor grade, clinical stage and lymph node metastasis. The increase of LVD may be related to the invasion and lymph node metastasis of BTCC.3. VEGF-D may promote lymphangiogenesis process in the BTCC, and induce tumor lymph node metastasis.4. The detections of VEGF-D and LVD in the tissue of BTCC could be accepted as important markers to evaluate the lymph node metastasis. It could predict the prognosis of BTCC and provide the experimental and theoretical foundation to formulate the clinical treatment methods.