Research On Relationship Between Lymphatic Metastasis And Expression Of VEGF-D, CXCR4 In Human Breast Carcinoma

OBJICTIVE To analyze the relationship between lymph node metastasis and expression of vascular endothelial growth factor D(VEGF-D) and CXCR chemokine receptor-4(CXCR4) in breast carcinoma.To elucidate the molecular mechanism of lymphatic metastasis in breast carcinoma and to provide a new method for carcinoma treatment.METHODS 53 case infiltrative ductal breast carcinoma,40 case atypical hyperplasia of breast and 20 case nomal breast tissue were choosen to detect VEGF-D and CXCR4 by immunohistochemical method.Lymphatic microvessel density(LMVD) was identified by D2-40 marker.RESULTS(1) The LMVD level in carcinoma group(17.68±4.07) was much higher than in hyperplasia group(11.26±3.12) and control(5.80±1.24)(P＜0.05).The LMVD level in peritumoral region(19.32±3.47) was much higher than in intratumoral region(10.91±2.07)(P＜0.05).The LMVD level in lymph node metastasis group(21.16±5.02) was higher than in no lymph node metastasis group(14.14±2.25)(P＜0.05).(2) The expression rate of VEGF-D were 64.2%(34/53) in carcinoma group, 30%(12/40) in hyperplasia group and 5%(1/20) in control.There was statistical difference between them(x~2=28.04,P＜0.05).The positive expression rate of VEGF-D were 87.1%(27/31) in lymph node metastasis group,31.8%(7/22) in no lymph node metastasis group.There was significant difference between them(x~2=17.10,P＜0.05).(3) The positive expression rate of VEGF-D in breast carcinoma had no correlation compared with age and expression of ER,PR,Cerb-2(P＞0.05 respectively),was significantly related to clinical stage,histological grade(P＜0.05 respectively).(4) The expression rate of CXCR4 were 52.8%(28/53) in carcinoma group,25% (10/40) in hyperplasia group and 10%(2/20) in control.There was statistical difference between them(x~2=22.02,P＜0.05).The positive expression rate of CXCR4 were 77.4%(24/31) in lymph node metastasis group,18.1%(4/22) in no lymph node metastasis group.There was significant difference between them(x~2=18.01,P＜0.05).(5) The positive expression rate of CXCR4 in breast carcinoma had no correlation compared with age and expression of ER,PR,Cerb-2(P＞0.05 respectively),was significantly related to the clinical stage and histological grade(P＜0.05 respectively).(6) The VEGF-D positive LMVD level(21.18±3.82) was higher than in VEGF-D negative(13.95±2.07)(P＜0.05).The CXCR4 positive LMVD level(19.18±3.32) had no significant difference compared with the CXCR4 negative(17.56±2.49)(P＞0.05).(7) The positive expression rate of VEGF-D had correlation compared with the positive expression rate of CXCR4 in breast carcinoma.(r=0.318 P＜0.05).Conclusion(1) The VEGF-D may induce lymphangiogenesis and promote the lymph node metastasis of breast carcinoma.The detection of VEGF-D has an important clinical significance in evaluating prognosis of tumor.(2) CXCR4 play a vital role in the tumor invasion,which have no correlation with the lymphgiogenesis in breast carcinoma.The high expression of CXCR4 may promote the lymph node metastasis of breast carcinoma by accelerating lympthatic invasion,which may be used as a valuable marker in assessing biological behavior and metastasis potential in breast carcinoma.(3) The new-born lymphatic vessels are found in breast carcinoma.The lymphatic vessels density level is much higher in the peritumoral region.Peritumoral lymphatic vessels may be an important pathway of nodal metastasis.(4) The increase of LMVD level is closely related to lymph node metastasis which indicate that the increase of LMVD level is an important procedure of lymphatic vessels metastasis.LMVD can be used as a tumoral metastasis index.(5)There is a synergistic effect between VEGF-D and CXCR4 in nodal metastasis of breast carcinoma,Combined detect of VEGF-D and CXCR4 is helpful to assessing prognosis.