Expression And Clinical Significance Of VEGF-C,VEGFR-3,HER-2 In Breast Cancer

Objective:Blood and lymph vessel angiogenesis, vascular permeability and endothelial cells are regulated by vascular endothelial growth factor family (VEGFs). VEGF-C is the ligand of VEGFR-3, and the affinity between VEGF-C and VEGFR-3 is increased through cleavage of the protein precursor.Also,VEGF-C binds to VEGFR-2,which promotes blood and lymph vessel angiogenesis inside tumor,and transfer of tumor cells.The aim of this project is investigating the expression of VEGF-C, VEGFR-3 and human epidermal growth factor receptor-2 (HER-2) in breast cancer tissues, discussing its consequences and relationship with other patho- logical factors, and establish a theoretical foundation for clinical diagno- stics and treatments.Methods: In order to study the expression of VEGF-C in invasive ductal carcinoma tissues, VEGFR-3, HER-2 and lymphatic vessel density (LVD) were measured using Immuno-Histo Chemistry approach (including 30 lymphatic metastasis samples and 25 non-lymphatic metastasis samples).Results:1.The expression of VEGF-C in cytoplast of breast cancer cells. Expression of VEGF-C was found in 81.8% (45/55) breast cancer tissue samples, and 93.3% (28/30) lymphatic metastasis tissue samples. On the other hand, only 68.0% (17/25) non-lymphatic metastasis samples express VEGF-C.According to this t-test,the two sets data are significantly different (P<0.05). In histological grade (I,â…¡,â…¢), VEGF-C expression was found in 54.5% (6/11) grade I samples, 87.5 % (21/24) grade II samples and 90.0%(18/20) grade III samples; the statistic analysis shows significant difference between each sample set (P<0.05). The expression of VEGF-C is not affected by age, menstrual status, tumor size, estrogen and progesterone receptor status (P>0.05).2.The expression of VEGFR-3 in cytoplast of breast cancer cells. Expression of VEGFR-3 was found in 72.7% (40/55) breast cancer tissue samples, and 86.7% (26/30) lymphatic metastasis tissue samples. On the other hand, only 56.0% (14/25) non-lymphatic metastasis samples expres- sing VEGFR-3, according to t-test, the two sets data are significantly di- fferent (P<0.05). In histological grade (I,â…¡,â…¢), VEGFR-3 expression was found in 63.6% (7/11) grade I samples, 66.7 % (16/24) grade II samples and 85.0%(17/20) grade III samples; the statistic analysis shows significant difference between each sample set (P<0.05). The expression of VEGFR-3 is not affected by age, menstrual status, tumor size, estrogen and proge- sterone receptor status (P>0.05).3.The expression of HER-2 in cytoplast and epicyte of breast cancer cells. Expression of HER-2 was found in 67.3% (37/55) breast cancer tissue samples, and 80.0% (24/30) lymphatic metastasis tissue samples. On the other hand, only 52.0% (13/25) non-lymphatic metastasis samples expressing HER-2, according to t-test,the two sets data are significantly different (P<0.05). In histological grade (I,â…¡,â…¢), HER-2 expression was found in 36.4% (4/11) grade I samples, 58.3 % (14/24) grade II samples and 95.0%(19/20) grade III samples; the statistic analysis shows significant difference between each sample set (P<0.05). Tumors were grouped into two data sets according to sizes; in the small tumor group (tumor diameter less than 2cm), 48.0% (12/25) samples were HER-2 positive; in the bigger tumor group, 83.3% (25/30) were HER-2 positive, the two samples sets are significantly different (P<0.05). The expression of VEGF-3 is not affected by age, menstrual status, tumor size, estrogen and progesterone receptor status (P>0.05).4.The positive rate expression of VEGF-C is higher than HER-2 , 30 out of 37 HER-2 positive samples are VEGF-C.5.The positive rate expression of VEGFR-3 is higher than HER-2, 28 out of 37 HER-2 positive samples are VEGFR-3.6.The level of LVD in VEGF-C positive and negative groups are significant difference (P<0.05) Conclusion:1.The presences of VEGF-C and VEGFR-3 have direct relationship with HER-2 expression;HER-2 is able to enhance the expression of VEGF- C and VEGFR-3. All three factors could be taken as index of breast cancer prognostic.2.The presences of VEGF-C, VEGFR-3 and HER-2 have direct rela- tionship with tumor histological grade and lymphatic metastasis.3.There is direct relationship between the expression of VEGF-C and LVD, the expression of VEGF-C might promote lymph angiogenesis inside tumor; lymphatic metastasis of breast cancer is related to high expression level of VEGF-C.