Expression Of MACC1 And C-Met In Breast Cancer And The Clinical Significance

Objective: Metastasis associated in colon cancer-1(MACC1)is a new gene discovered by whole genome Scans by Stein in 2009.It is a very important regulatory factor of the HGF/c-Met signaling pathway that can regulate expression of c-Met.It plays a part in malignant transformation,cells invasion and the metastasis process of tumors,thus can be used to predict the risk of postoperative recurrence and metastasis.Currently,the views on the role of MACC1 and c-Met protein in the invasion and metastasis of breast cancer remain a matter of debate.some researchers think MACC1,c-Met protein has a great influence on the ability of proliferation,migration and related to the prognosis in breast cancer,but others hold different views.In this study,we detect the expression of MACC1 and c-Met in normal breast tissue,ductal carcinoma in situ(DCIS),DCIS with micro-invasive(DCIS-Mi)and invasion ductal carcinoma(IDC)from breast cancer patients by immunohistochemical for the first time.The different expressions in breast tissues were analyzed and the correlation between the expression of MACC1,c-Met and tumor clinical pathological in IDC patient was also analyzed.Our results provide more evidence for MACC1 and c-Met in breast cancer research.Methods: A total of 217 patients were collected at Department of Breast Surgery in affiliated hospital of Southwest medical university,from January 2014 to May 2015.Samples were divided into four groups,including 132 cases of IDC group,36 cases of DCIS-Mi group,29 cases of DCIS group and 20 cases of normal tissue group.The expressions of MACC1 and c-Met were detected by envision immunohistochemistry,and different expressions in breast tissues were analyzed.The correlation between the expression of MACC1,c-Met and tumor clinical pathological in IDC patient was also analyzed.All datas were analyzed by SPSS 17.0 statistical software system.The chi-square test method was applied to examine the count data,Fisher's exact test to pairwise comparison,Pearson correlation test to the correlation analysis.and value of P<0.05 denoted a statistically significant difference.Results:1.The positive expression ratios of MACC1 in four groups of breast tissues,normal breast tissues,DCIS,DCIS-Mi and IDC were 5%,34.5%,61.1% and 63.6%,respectively,the difference had reached significant level(P=0.000).The positive expression ratios of MACC1 in IDC,DCIS-Mi,DCIS tissues were much higher than normal tissue,the difference reached significant level(P<0.05).The positive expression ratios of MACC1 in IDC,DCIS-Mi groups were higher than that in DCIS group,the difference reached significant level(P<0.05).However there was no statistical difference between DCIS-Mi and IDC group(P>0.05).2.The positive expression ratios of c-Met in four groups of breast tissue including normal tissue,DCIS,DCIS-Mi and IDC were 5%,27.6%,58.3% and 64.1%,respectively,the difference reached significant level(P=0.004).The positive expression ratios of c-Met in IDC,DCIS-Mi,DCIS tissues were much higher than normal tissue,with significant difference(P<0.05).The positive expression ratios of c-Met in IDC,DCIS-Mi groups were higher than that in DCIS group,the difference reached significant level(P<0.05).However there was no statistical difference between DCIS-Mi and IDC group(P>0.05).3.The expression of MACC1 protein in IDC was significantly related to tumor size(P=0.004),lymphatic metastasis(P=0.019),distant metastasis(P=0.031),pTNM stage(P=0.006),WHO grade(P=0.008),vascular invasion(P=0.021),recurrence risk(P=0.000)and expression of ER(P=0.029),HER-2(P=0.013)(P<0.05).But there was no statistical difference in age,PR,Ki-67 and molecular subtyping(P>0.05).4.The expression of c-Met protein in IDC was significantly related to lymphatic metastasis(P=0.012),distant metastasis(P=0.004),pTNM stage(P=0.007),WHO grade(P=0.007),vascular invasion(P=0.024),recurrence risk(P=0.001)(P<0.05).there was no statistical difference in age,ER,PR,HER-2,Ki-67 and molecular subtyping(P>0.05).5.The expression of MACC1 protein was positively correlated with the c-Met protein in IDC(r=0.619,P=0.015)by Pearson correlation test result.Conclusions:1.The positive expression ratios of MACC1 and c-Met protein in normal tissues,DCIS,DCIS-Mi and IDC showed an increasing tendency.The positive expression ratios in IDC,DCIS-Mi groups were higher than that in DCIS group.But there was no statistical difference between DCIS-Mi and IDC group.Induced that MACC1,c-Met probably associated with tumor invasive capability and were an early event in the process of breast cancer.2.In IDC,the advanced pTNM stage,lymphatic metastasis,distant metastasis,vascular invasion,high WHO grade,and high recurrence risk groups MACC1 and c-Met protein were high expression which indicated that MACC1 and c-Met might involve in the invasion and metastasis of breast cancer.3.The expression of MACC1 protein in IDC is positively correlated with the c-Met protein.it suggested that MACC1 and c-Met may play a synergetic effect in the progression and metastasis of breast cancer.