Expressions Of VEGF-C And VEGF-D And Their Correlation With Lymphangiogenesis And Angiogenesis In Gallbladder Carcinoma

【Objective】Lymph node metastasis is the most common form of progression in gallbladder cancer. Whereas VEGF-C and-D have well-defined actions on neoplastic lymphangiogenesis and angiogenesis though VEGFR-3 and VEGFR-2 respectively, the function of the VEGF-C/VEGF-D/receptors pathway in gallbladder carcinoma is largely unknown. Based on reason above, we try to approach expressions of VEGF-C and VEGF-D and their correlation with lymphangiogenesis and angiogenesis in gallbladder carcinoma tissue. All those will provide the experimental foundation for anti-lymph angiogenic therapy in gallbladder cancer.【Methods】Fifty cases of gallbladder carcinoma with complete clinical and pathological data were analyzed. The expression of VEGF-C and-D, D2-40, CD31 was assayed by immunohistochemical staining, with 10 samples of normal gallbladder tissues away from cancer and 19 samples of chronic cholecystitis as controls. Establish a semi-quantitative score the level of VEGF-C and VEGF-D expression and analyse the relationship between the expression of VEGF-C,VEGF-D, MLVD and MVD. And also their correlation with clinicopathological findings were analyzed retrospectively.【Results】Thirty-two (64%) of the 50 gallbladder cancers were positive for VEGF-C protein expression by immunohistochemistry and the positive rate of VEGF-D protein expression was 62.0%(31/50). The protein expression of VEGF-C and VEGF-D in tumor tissues was significantly higher than that in normal gallbladder tissues away from the tumor (P<0.05), but no correlation with that in chronic cholecystitis (P<0.05).The immunoreactivity for VEGF-C and VEGF-D was more intense at the site of deepest invasion than at the central portion or superficial part of the tumor. The VEGF-C expression correlated with the patient age and lymph node metastasis (both P<0.05). The VEGF-D expression only correlated with lymph node metastasis (P<0.05). In the 50 gallbladder cancers, the MLVD was 6.9±3.6 and the MVD was 36.1±12.8. The MLVD in both VEGF-C and-D positive groups was significantly higher than that in the negative groups (P= 0.000), and the lymph node metastasis also increased. MVD in both VEGF-C and-D positive groups was higher than that in the negative groups (P<0.05), and it was also correlated with tumor differentiation (P<0.05). A significant positive correlation was also found between VEGF-C and VEGF-D expression (r= 0.498, P= 0.000). In the 10 chronic cholecystitis, the MLVD in both VEGF-C and-D positive groups was significantly higher than that in the negative groups(P<0.05), and MVD in VEGF-D positive group was higher than that in the negative group (P<0.05).【Conclusion】VEGF-C and VEGF-D are involved in the lymphangiogenesis and angiogenesis in gallbladder carcinoma, promote lymph node metastasis of the tumor, and both are important in the regulation of lymphangiogenesis and angiogenesis in this cancer. VEGF-C and VEGF-D are of clinical significance in evaluating lymph node metastatic potency and estimation of prognosis in gallbladder carcinoma.