[Roles of VEGF-C and its receptor Flt-4 in proliferation and metastasis of primary breast cancer].
OBJECTIVE
Vascular endothelial growth factor-C(VEGF-C) is a member of VEGF family and the only factor that can combine receptor VEGFR-3 (fms-like tyrosine kinase, Flt-4) located at endothelium of lymphatic vessel and modulates the physiological function of lymphatic vessel. Previous study showed that VEGF-C/Flt-4 system play a modulating role in metastasis of many kinds of tumors, but there were few reports about its function for primary breast cancer at home and abroad. The objective of this study was to identify the function of VEGF-C/Flt-4 system in proliferation and metastasis of primary breast cancer and its significance.


METHODS
A series of 101 primary breast cancer specimens were detected for the expression of VEGF-C, Flt-4,and PCNA by Immunohistochemical methods.


RESULTS
Among 101 cases of breast cancer, the positive rate of VEGF-C was 93.1% (94/101), the positive rate of flt-4 was 86.1% (87/101). With the increase of the expression of VEGF-C, the positive index of flt-4 increased (r=0.816,P< 0.001). The positive rate of PCNA was 88.8% (89/101). With the increase of the expression of VEGF-C, the proliferation activity of PCNA was stronger (r=0.673,P< 0.001). The positive index of VEGF-C in lymph node metastases group (61.89+/-17.79) was significantly higher than that of no lymph node metastasis group (44.28+/-17.87)(P< 0.05). With the increase of VEGF-C protein level, the number of flt-4 positive vessels increased and significant differences among these groups were observed (P< 0.001). The number of flt-4 positive vessels in lymph node metastases group (15.55+/-3.63)was significantly higher than that of no lymph node metastasis group (10.71+/-2.90 ) (P< 0.05).


CONCLUSIONS
VEGF-C and Flt-4 are overexpressed in primary breast cancer and related to lymph node metastasis. VEGF-C can promote proliferation of breast cancer cell. VEGF-C/flt-4 system can promote vasculogenesis in stroma of breast cancer. The number of Flt-4 positive vessels is closely related to lymph node metastasis.
Liu
Fang
F
Department of Pathology, The First Affiliated Hospital of Guangzhou Medical Colledge, Guangzhou, Guangdong, 510120, PR China. gyliufang@hotmail.com
Zhang
Ya-Jie
YJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis / Q000502:physiology*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis / Q000502:physiology*
D018809:Proliferating Cell Nuclear Antigen; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3