The Study Of Correlation Between Expression Of VEGF-C/D In TAMs And Lymphatic Metastasis In Breast Cancer

Objective To analyze the relationship between the expression of vascular endothelial growth-C/D(VEGF-C/D) in tumer-assoiciated macrophages(TAMs) and lymphatic metastasis in breast cancer.To provide new channel for diagnosis,treat and prognosis of breast cancer.Methods CD₆₈,VEGF-C,VEGF-D and D_2-40 were detected by immunohistochemistry technique SP in 53 cases of breast cancer,30 cases of benign lesion and 20 cases of normal breast tissue.TAMs and microlymphatic vessel density (MLVD) were marked by CD₆₈ and D_2-40 antibody respectively;The double staining was also used to determine VEGF-C and VEGF-D expression in TAMs.Results 1.D_2-40 expression in breast cancer(1) The MLVD level in breast cancer(17.79±4.02) was much higher than in benign lesion(6.43±2.42) and normal tissue(2.00±1.03)(P＜0.01);The MLVD level in peritumoral region(17.75±3.99) was much higher than in intratumoral region(8.68±3.38)(P＜0.01);The MLVD level in lymph node metastasis group(20.71±1.81) was higher than in no lymph node metastasis group(13.68±2.23)(P＜0.01).(2) The MLVD in breast cancer had no correlation compared with age,clinical stage and the expression of ER,PR,Cerb-2(P＞0.05,respectively);but there was statistical difference between histological gradeâ… ,â…¡andâ…¢(P<0.05),the expression of MLVD in gradeâ…¢(20.76±2.22) was much higher thanâ… (14.76±2.75) andâ…¡(17.84±4.30).2.CD₆₈ expression in TAMs of breast cancer(1) The positive expression rate of CD₆₈ in TAMs were 58.50%(31/53) in breast cancer,13.33%(4/30) in benign lesion and 15.00%(3/20) in normal tissue,there was statistical difference between them(x²=21.89,P＜0.01);The positive expression rate of CD₆₈ in TAMs were 74.20%(23/31) in lymph metastasis,36.36%(8/22) in no lymph metastasis,there was significant difference between them(x²=7.59,P＜0.01).(2) The CD₆₈ positive expression rate in TAMs of breast cancer in histological grade(â… ,â…¡andâ…¢) were 35.29%(6/17),63.16(12/19) and 76.47(13/17) respectively, there were statistical difference between them(P＜0.05);It had no correlation compared with age,clinical stage and the expression of ER,PR,Cerb-2(P＞0.05,respectively).(3) The CD₆₈ positive MLVD level(18.81±3.80) was higher than in CD₆₈ negative (16.36±3.96)(P＜0.05);The CD₆₈ expression in TAMs was related to the level of MLVD (r_s=0.418,P=0.002),That is,with the expression of CD₆₈ in TAMs enhanced,the level of MLVD also enhanced.3.The expression of VEGF-C and VEGF-D in breast cancer(1) The positive expression rate of VEGF-C and VEGF-D respectively were 52.83% (28/53) and 49.06%(26/53) in breast cancer,10.00%(3/30) and 13.33%(4/30) in benign lesion,both were 10.0%(2/20) in normal tissue,there were statistical difference between them(P＜0.01,respectively);The positive expression rate of VEGF-C and VEGF-D both were 70.97%(22/31) in lymph node metastasis group,27.27%(6/22) and 18.18%(4/22) respectively in no lymph node metastasis group,there were significant difference between them(P＜0.01,respectively).(2) The expression of VEGF-C and VEGF-D in breast cancer had no correlation compared with age,clinical stage and the expression of ER,PR(P＞0.05,respectively);but there were statistical difference between histological grade(P＜0.05,respectively);In addition,The expression of VEGF-C were significantly related to the expression of Cerb-2(3) The VEGF-C and VEGF-D positive MLVD level were(19.25±3.20) and(19.58±3.09) respectively,VEGF-C and VEGF-D negative MLVD level were(16.16±4.26) and (16.07±4.10) respectively,there were statistical difference between them(P＜0.01, respectively);The VEGF-C and VEGF-D expression were related to the level of MLVD (r_s=0.413,P=0.002 and r_s=0.426,P=0.001),That is,with the expression of VEGF-C and VEGF-D in breast cancer enhanced,the level of MLVD also enhanced.4.VEGF-C and VEGF-D expression in TAMs of breast cancer(1) The double immunohistochemical staining showed that VEGF-C and VEGF-D positive expression in TAMs respectively were(17.15±4.17) and(14.05±3.32) of breast cancer,which occupied total number of TAMs(97.95±12.40) about 11.5%-21.4%and 9.0%-17.7%,the mean of them were 17.3%and 14.2%.(2) VEGF-C and VEGF-D expression in TAMs of breat cancer were both related to the number of TAMs(r_s =0.490 and r_s=0.464)(P＜0.05,respectively). Conclusions 1.TAMs may play a major role in peritumoral lymphatic neoangiogenesis and lymphatic metastasis,which may be used as a new target in diagnosis and treating of breast cancer.2.The new-born lymphatic vessels were found in breast cancer.The microlymphatic vessels density(MLVD) level in the peritumoral region is much higher than intratumoral region,it may be an important pathway of nodal metastasis in breast cancer.The MLVD is closely related to lymphatic metastasis,it could be used as a tumoral metastasis index in breast cancer.3.VEGF-C and VEGF-D participate in lymphangiogenesis and promote the lymphatic metastasis of breast cancer.4.The positive expression rate of CD₆₈ in TAMs have high positive expression rate of VEGF-C and VEGF-D,it indicates that turner cells and TAMs both secrete VEGF-C,VEGF-D in breat cancer,TAMs,VEGF-C and VEGF-D are speculated to have synergistic effect in growth,invasion and metastasis process of breast cancer.