Vascular Endothelial Growth Factor-C Expression In Carcinoma Of Endometrium And Its Relationship To Lymph Node Metastasis

Object: (1) To investigate the expression of VEGF-C, and its receptor, VEGFR-3 in carcinoma of endometrium. (2) To analysis the relationship between VEGF-C, LVD(lymphatic vessel density), which marked with podoplanin and VEGFR-3, and lymph node metastasis. To detect the mechanism of lymphatic invasion in cancer.Methods: To detect the expression of VEGF-C in carcinoma of endometrium,normal endometrium and endometrial hyperplasia by using immunohistochemical staining. The lymphatics wihich marked with podoplanin and VEGFR-3 were counted in tumor tissue and its lymph node.Results: (1) No VEGF-C was expressed in normal endometrium and endometrial hyperplasia. (2) VEGF-C was found in cytoplasm, it presented in 77.80% of cases in carcinoma of endometrium. (3) Expression of VEGF-C was much higher in lymph node-positive group (88.00%) than that of lymph node-negative group (65.00%) (P=0.004); the stage of III-IV (82.14%) was higher than that of I -II (70.59%) (P=0.042). It had no significant correlation with differentiation and pathologic types (P>0.05). (4) Podopalnin was found in cytoplasm of lymphatic endothelial cell (LEC), which presented between tumor and normal tissues. (5) VEGFR-3 was found in cytoplasm, wihich mainly distributed in LEC, and also presented in micro blood vessels and matrix. (6) The number of podoplanin-positive and VEGFR-3-positive vessels was higher in VEGF-C-positive group (P=0.028); LVD was much higher in lymph node-positive group than that of lymph node-negative gruoup (P=0.01). It had no significant correlation with tumor stage,differentiation and pathological types. (7) A strong correlation was found between VEGF-C expression and LVD,lymph node metastasis (P=0.001, r=0.460; P=0.003, r=0.439). Futhermore, there was a close correlation between LVD and lymph node metastasis (P=0.008, r=0.391).Conclusion: (1) High expression of VEGF-C may influence the pathogenesis of lymph node metastasis in carcinoma of endometrium. (2) Excepting LEC, VEGFR-3 also presented in micro blood vessel and matrix; podoplanin only presented in LEC. The result was more specific and precise by using podoplanin and VEGFR-3 to mark lymphatic vessel, which depleted the influence of micro blood vessel. (3) VEGF-C, produced by tumor cells, may induce the proliferation of lymphatic vessels through VEGFR-3, resulting in the development of invasion of cancer cells into the lymphatic vessel and lymph node metastasis.