Clinical Value Of Tissue HER2mRNA Expression And Serum Protein Level In Primary Breast Cancer By Quantitative Detection

Background:The proto-oncogene HER2, also named C-erbB-2or Her-2/neu, coding185,000bp transmembrane protein p185,which has the activation of transmembrane protein tyrosine kinase,HER2protein extracellular region fragment HER2ECD is the section of glycosylated receptor protein,it can be split from cellular membrane into peripheral blood circulation.HER2is express widely in epidermal growth factor receptor family.It can suppress the apoptosis of tumor cell, promote tne angiogenesis of tumor new vessels, increase the invasiveness of tumor cells, destroy the anti-invasion barrier of organism tissue, thus promote tumor progression. Many study discover that the tumor cells with HER2overexpression were not insensitivity to chemotherapy, thus, it can be recognized as a prognostic marker of the sensitivity of chemotherapy in breast cancer, it is an important target of molecule targeted therapy of breast cancer. At present, most of the studies’ findings show that the overexpression of HER2protein may show a worse prognosis of breast cancer pateins, but there still were some study shou that HER2has no obviously significance for breast cancer pateins’prognosis.Objective:Quantitative analysis a larger number of clinical cases’ primary breast cancer tissues’HER2mRNA express levels, elucidate the relationship between tissue HER2mRNA、serum HER2protein expression and tissue HER2protein express levels. Analyses the correlation between clinicopathologic factors and tissue HER2mRNA、 serum HER2protein expression levels. Evaluate the clinical value of HER2in breast cancer differential diagnosis and prognosis.Methods:Use Real-time reverse transcription-polymerase chain reaction (QRT-PCR) assay to detect the HER2mRNA levels of233mammary gland infitrating ductal carcinoma; Receiver Operating Characteristic (ROC) curve was used to identify the cut-off value of KIF1B mRNA level to group the patients. Chi square test was used to compare the differences between/among groups. Survival analysis was carried out according to Kaplan-Meier analysis. Log-rank test was used to compare the differences of survival between groups. Cox proportional hazards regression model was used to evaluate the significance of HER2mRNA level for predicting the prognosis of breast cancer patients.protein dot-blot assay and enzyme-linked immunosorbent assay(ELISA) detect56patiens with mammary gland innocuousness disease and133primary breast cancer patiens’ serum HER2protein levels. Chi square test was used to compare the differences between/among groups.Rank-sum test to compare the differences between patiens with mammary gland innocuousness disease and133primary breast cancer patiens’serum HER2protein levels.Results:The correlations between primary breast cancer HER2mRNA and breast cancer: Spearman rank correlation analysis show that the dependability between breast cancer tissue HER2mRNA and HER2protein is good(r=0.860, P=0.00006).ER-negative, PR-negative cases’HER2mRNA is higher than ER-positive、PR-positive cases(P=0.000, P=0.000).There were no statistics difference between age menopausal state、tumor size、clinical stage、histology grade、lymphoid node state(P>0.05).Low HER2mRNA level group and high HER2mRNA level groups’ disease free survival and non metastases survival are lower than middle HER2mRNA level group(P=0.008, P=0.0005); Low HER2mRNA level group and high HER2mRNA level groups’three years disease-free survival and metastasis-free survival and five years disease-free survival and metastasis-free survival are lower than middle HER2mRNA level group(P=0.014, P=0.002;P=0.050, P=0.016). The clinical stage and node-positive numbers and PR status were independent prognostic factors of breast cancer by analysis of Multivariate Cox proportional hazards regression model. HER2status was not an independent prognostic factors in this study.The correlations between serum HER2protein and breast cancer:Spearman rank correlation analysis show that the dependability between breast cancer serum HER2protein and tissue HER2protein is good(r=0.568, P=0.016). The serum HER2levels of patients whose tumor diameter is smaller than2cm is lower than patients whose tumor diameter is larger than2cm; serum HER2protein levels of patients whose lymphoid node-positive numbers are more than4is lower than patients whose lymphoid node-positive numbers are fewer than4(.P=0.028); PR-positive breast cancer patients’serum HER2protein levels is lower than PR-negtive patients(P=0.012).Breast cancer patients’serum HER2level is higher than mammary gland innocuousness patients(P=0.045).Conclusion:HER2mRNA levels in primary breast cancer tissue is coincidence with HER2protein levels in breast cancer tissues, its expression is associated with ER、PR states. Low and high HER2mRNA level have a poor prognosis. All of these show that Her2mRNA can be used to direct chemotherapy plan, evaluate breast cancer patients’ prognosis.Serum HER2protein levels is coincidence with HER2protein levels in breast cancer tissues,it show that serum HER protein can be used to dynamic monitoring the state of post-operation patients, participate the direction chemotherapy plan, guide the molecular argeted therapy. Serum HER2protein levels has positive correlation with tumor size and the number of positive numbers, high levels of serum HER2protein is correlation with the progression of breast cancer. Breast cancer patients’serum HER2level is higher than mammary gland innocuousness patients...