The Role Of Hepatocyte Growth Factor In Tumor Proliferation And Angiogenesis In Breast Cancer

【Background and Objective】Hepatocyte growth factor(HGF ), also known asScatter factor(SF), is a pleiotropic growth factor that induces tumor cell proliferation,invasion and metastasis, and tumor angiogensis. The aim of this study is to investigatethe expression level of HGFmRNA and the role of it in tumor proliferation andangiogenesis in breast cancer so as to offer the theoretic basis to the mechanism ofbreast cancer; At the same time, the relationship between HGF and prognosis of breastcancer patient was also explored in order to provide the theory of the possibility of anew prognosis predictor for breast carcinoma.【Methods】In situ hybridization method was used to detect the expression levelof HGFmRNA in 75 cases of full follow-up invasive ductal breast cancer and 10 casesof benign breast tumor tissues. The expression level of HGF was judged by the totalscores of the strength of staining and the percentage of positive cells per 1000 countedneoplastic cells for each case. S-P immunohistochemical staining was also used todetect the expression level of K_i67 and MVD in 75 cases of invasive ductal breastcancer tissues. MVD were highlighted by staining their endothelial cellsimmunohistochemically for CD34, and then were counted in the most intense areas ofneovascularization. The expression of K_i67 was judged by the percentage of positivecells per 1000 counted neoplastic cells for each case. Correlation between HGF, andK_i67 and MVD were statistically analyzed in order to explore the role of HGF intumor proliferation and angiogenesis in breast cancer. At last, Kaplan-Meier methodand Cox proportional hazard regression model were used to assess the value of HGFin breast cancer prognosis.【Results】It was found that the expression level of HGF in breast cancer wassignificantly higher than that in breast benign tumor(72% VS 10%, P<0.05);Theexpression level of K_i67 and the value of MVD in tumor with positive HGFexpression were significantly higher than those with negative HGF expression(p<0.05), and there was a closely positive correlation among HGF, Ki67 and MVD,and the correlation coefficient were 0.450 and 0.520, respectively(both P<0.05); Theexpression level of Ki67 and the value of MVD in patients with positive lymoph nodemetastasis were significantly higher than those with negative lymoph node metastasis(p<0.05), and there was also a closely positive correlation among Ki67, MVD andlymoph node metastasis , the correlation coefficient were 0.305 and 0.353,respectively(both P<0.05); The expression of HGF has no significantly correlationwith age, lesions position, menopausal status, ER and PR (p>0.05), but hassignificantly correlation with tumor size, histological grade, TNM stage and lymophnode metastasis (p<0.05); Breast cancer patients with positive HGF expression hadsignificantly lower overall survival rate (OS) and disease free survival rate (DFS)when compared to those with negative HGF expression (p<0.05). In multivariate coxregression analysis, HGF was found to be the most important independent factor inpredicting patients' prognosis, even of greater import than lymoph node metastasis(RR=5.650). 【Conclusions】The results of experiment suggest that HGF was overexpressedin breast cancer tissue, and the overexpression of HGF was associated with tumoroccurrence, histological grade, TNM stage and lymoph node metastasis in patientswith breast cancer, which means that HGF may be a useful maker which can identifyhigh aggressive and metastatic potential in patients with breast cancer at early age.HGF was closely related with tumor proliferation and tumor angiogenesis, it mightplay a positive role in tumor invasion and metastasis by inducing tumor proliferationand tumor angiogenesis. HGF could be one of valuable prognosis indicators in breastcancer.