[Study of the correlation between HER-2 gene and lymphangiogenesis and their prognostic significance in human breast cancer].

Objective To demonstrate the molecular mechanism of poor prognosis in HER-2 overexpressing breast carcinoma,to study the correlation between angiogenesis/lymphangiogenesis and HER- 2,and the effect of them in the progression and prognosis,so as to provide novel molecular markers for lymph node metastasis and prognosis in breast carcinoma.Methods(1)By using TaqMan real-time quantitative reverse transcription polymerase chain reaction(real-time qRT-PCR)technique and immunohistochemistry(IHC),the mRNA and protein expression of VEGF-C were detected in SKBR-3 and MDA-MB-231 cell lines before and after the interference with Herceptin.(2)Real-time qRT-PCR was performed to detect the mRNA expression of VEGF-C and -D genes in 67 cases of primary breast infiltrating ductal carcinoma.(3)160 formmalin-fixed paraffin-embedded infiltrating duetal carcinomas were selected. The protein expression of HER-2,VEGF-C,lymphatic vessel density(LVD)and lymphatic vessel invasion (LVI)were detected by IHC.Result(1)After interference with Herceptin,the VEGF-C mRNA and protein expression of sKBR-3 the cells decreased significantly.In primary breast cancer,the protein expression of HER-2 was positively correlated with VEGF-C protein expression(r=0.215,P0.05). There was a significantly positive correlation between VEGF-C protein expression and LVD(r=0.248,P 0.01).(2)VEGF-C mRNA expression in the patients with lymph node metastasis was higher than that in the patients without lymph node metastasis(1.6±0.5 vs 1.1±0.5)(t=2.196,P0.05).Logistic regression model showed HER-2,LVD and LVI were important factors influencing lymph node metastasis(all P0.05).(3)Kaplan-Meier analysis indicated that HER-2 protein overexpression,VEGF-C protein overexpression,and high LVD and LVI were associated with patient's worse disease-free survival(P_(uni) 0.05).Cox regression analysis indicated that HER-2 and LVI were the independent prognostic factors of breast cancer(both P_(mult0.05).Conclusion Through up-regulating VEGF-C expression,HER-2 overexpression induces lymphangiogenesis,promotes metastasis,and results in the poor prognosis of breast cancer.VEGF-C expression,LVD and LVI are novel prognostic indicators of breast cancer.