| Research backgroundBreast cancer is one of the malignant tumors which seriously harm the physical and mental health of women. The pathogenesis of breast cancer is complicated, and there are many factors that affect the breast cancer. With the change of people’s life style and environment, the incidence of breast cancer in our country increased significantly, and showed a trend of youth. Due to the heterogeneity of breast cancer, there were differences in treatment response and prognosis in patients. With the development of molecular biology, especially genetic science, this difference is due to the difference of gene level. In recent years, it is a hot research topic to search for new molecular markers for breast cancer patients to provide better personalized treatment.MET(Mesenchymal-epithelial transition) is located in 7q31, which is a member of the tyrosine kinase family and its ligand is HGF(Hepatocyte growth factor). MET with the ligand binding by the receptor kinase domain dimerization and cytoplasm of auto phosphorylation, leading to activation of intracellular signaling pathways. MET signaling pathway plays an important role in maintaining the physiological function of normal tissues, including embryonic development, blood vessel formation, cell growth and wound healing. Activation of HGF/MET in the development of cancer can lead to invasion, cell proliferation, angiogenesis, cell migration, and the proliferation of blood vessels. Because the value of the met gene, gene copy number increase, gene mutation or receptor overexpression leads to tumor, such as breast cancer, non small cell lung cancer, gastric cancer, esophageal cancer, uterine endometrial cancer, liver cancer, head and neck cancer, rectal cancer and renal cancer. The activation of abnormal HGF/MET signaling pathway in these tumors is closely related to the malignant degree and the prognosis of the tumor. Studies have indicated that MET plays a key role in acquired drug resistance through interactions with other pathways, such as the RTKS family, especially EGFR.EGFR(Epidermal growth factor receptor) is the product of c-erb B-1 gene is located in 7p11-13, one of the four members of the epidermal growth factor receptor family. The intracellular region(tyrosine kinase domain), extracellular region and tyrosine kinase active ligand transmembrane region, a short film by(ligand binding domain). EGFR can be a large number of ligands including growth factor activation of epidermal growth factor(EGF) and transforming growth factor alpha(TGF- alpha). The combination of EGFR and ligand leads to tyrosine kinase phosphorylation of residues, induced downstream signal. The activation of epidermal growth factor tyrosine residues in the ligand dependent region as the signal sensor and the binding sites of regulatory proteins to regulate intracellular matrix signal flow. Phosphatidylinositol 3 kinase(PI3K) and Akt pathways and pathway of RAS/MAPK is the main signal mechanism and their role is control important biological functions including cell proliferation, survival, angiogenesis and metastasis to resist cell apoptosis. Studies have confirmed that in many malignant tumors(metastatic breast cancer, non small cell lung cancer) EGFR overexpression occurs.In the study of pancreatic cancer, non small cell lung cancer, MET and EGFR in the study found that there is a complex interaction between the pathways, and participate in the occurrence, development and metastasis of the tumor. But the two expression in breast cancer and its relationship with the current literature are rarely reported. The experimental group was treated with immune of IHC(Immunohistochemistry) and FISH(the molecular fluorescence in situ hybridization) was used to detect breast cancer type in the met gene, EGFR protein expression and gene amplification. To further elaborate the relationship between the two types of breast cancer molecular classification, clinical pathological indicators and the correlation between the two.Materials and methods:Study subjects: collected from the First Affiliated Hospital of Zhengzhou University from 2011 to 2015, 100 cases of breast cancer were diagnosed by surgical resection and pathological diagnosis. All cases did not receive radiotherapy, chemotherapy, endocrine therapy before surgery. Operation methods include breast cancer radical mastectomy, modified radical mastectomy, breast conserving and axillary lymph node dissection. According to the expression of ER, PR, HER-2 and KI67 in pathological report, the paraffin blocks were divided into different types.Methods: using immunohistochemical streptavidin biotin peroxidase method(SP method) and fish(fluorescence in situ hybridization) detection met and EGFR protein in the tissue expression. Statistical analysis using statistical software spss21.0, using non parametric test Kruskal Wallis h test(Wilcoxon test) analysis Met and EGFR in breast cancer molecular classification of expression with Spearman method to analyze the correlation between met and EGFR genes, Mann Whitney U rank sum test analysis met and EGFR and clinical pathological parameters, P < 0.05 for differences were statistically significant.Result:1 The positive rate of MET protein is 20% in breast carcinoma. The met protein in the luminal a subtype of breast cancer positive rate is 13%, in luminal B breast cancer positive rate is 0. In basal like breast cancer, the positive rate is 52%, in HER-2 positive breast cancer, the positive rate is 10%. The expression of MET protein is mainly expressed in the basal like breast.P<0.052 The positive rate of EGFR in breast cancer is 17%. The positive rate of EGFR protein in the lumen of A in breast cancer was 0 in luminal B breast cancer positive rate is 0, the positive rate in the basal cell type in breast cancer is 63%, the positive rate in HER-2 positive breast cancer is 0. The expression of EGFR protein is mainly expressed in the basal cell like breast cancer. P<0.053 The expression of MET protein is significantly correlated with EGFR protein in breast cancer, r=0.572,P < 0.054 In breast cancer, MET gene amplification in 15 cases, the positive rate is 15%. The HER-2 positive and luminal B breast cancer without gene amplification; in luminal a type amplification in 2 cases(positive rate of 5%); In BLBC amplification of 13 cases(positive rate was 48%) and MET gene is mainy amplificated in basal like breast cancer. P<0.055 Among breast cancer, EGFR amplification in 14 cases, the positive rate is 14%. But no amplification is found in Luminal Atype, HER-2 positive type and Luminal B type. 14 cases are amplified in BLBC type breast cancer(positive rate 52%), the EGFR gene is amplified in basal like breast cancer. P<0.056 Amplification of MET gene is associated with EGFR gene amplification r=0.686,P<0.05.7 The amplification of MET gene is positively correlated with the expression of MET protein r=0.701,P<0.05.8 The amplification of EGFR gene is positively correlated with the expression of EGFR protein r=0.928,P<0.05.9 MET gene has not connect with the patient’s age, menopausal status, tumor size, lymph node metastasis, histological grade P>0.05, but it is related to the TNM stage, P<0.05.10 EGFR gene has not associate with the patient’s age, menopausal status, tumor size, histological grade P>0.05, but it is related to the TNM stage and lymph node metastasis, P<0.05.Conclusion:The expression of MET gene and EGFR gene is closely related to basal like breast cancer, and the analysis of the two is helpful to predict the prognosis of basal like breast cancer, and provide theoretical basis for clinical treatment. |
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