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Expression Of PD-L1 In Breast Cancer And Its Clinical Significance

Posted on:2018-07-03Degree:MasterType:Thesis
Country:ChinaCandidate:C D FengFull Text:PDF
GTID:2504306575983629Subject:Oncology
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BackgroundNowadays,population-based medical research is being replaced by individualized precision medicine research,and tumor-targeted therapy is gradually replacing the traditional chemotherapy.Immunotherapy and tumor immunity has become the current medical research hotspot.Program cell death-ligand 1(PD-L1)is a transmembrane molecule belonging to the B7 immunoglobulin superfamily with a molecular weight between 40 kd and 50 kd.Its gene locates on human chromosome9p24.2.PD-L1 is a transmembrane protein molecule consisting of 290 amino acid subunits whose extracellular segment consists of immunoglobulin constant region Ig C and Ig V-like domains.PD-L1 is widely expressed on a variety of cell surfaces including natural killer cells,macrophages,myeloid dendritic cells,T cells,B cells,epithelial cells,vascular endothelial cells and so on.Moreover,a variety of solid tumor cell surfaces(non-small cell lung cancer,melanoma,renal cell carcinoma,breast cancer)are highly expressed PD-L1 molecules.The PD-1/PD-L1 signaling pathway,composed of programmed cell death-1(PD-1),is a physiological regulator of cell proliferation and growth factor production,and plays an important role in the activation of T cells and the regulation of the immune response.It has been found that PD-L1’s functions in vivo not only to activate T cells,but also to inhibit T cell-mediated immune response and promote the expression of PD-L1 tumor cells to escape the discern and wound of immune system.PD-L1 is highly expressed in tumor and plays an important role in tumorigenesis and development,making it possible to be a new target and tumor marker for tumor immunotherapy.At the same time,the drug clinical trials targeting PD-1/PD-L1 signaling pathway have also made important progress.Breast cancer is the most common malignancy in women,the incidence of which is increasing year by year.Breast cancer traditional treatment methods,including surgical treatment,radiation therapy and biological therapy.With the application of molecular immunology in the treatment of breast cancer,many immunological molecular markers have also become a hot topic in breast cancer research,such as ER,PR,her-2,Ki-67.They have become a routine immunization group of breast cancer patients.Recent studies have shown that the PD-1/PD-L1 signal pathway blockers show varying degrees of efficacy for PD-L1 solid tumors.San Antonio breast cancer symposium(SABCS)announced the results of a cohort study of early experiments,the results showed the PD-L1 express triple negative positive of metastatic breast cancer,keytruda total remission rate was 18.5% after treatment,the experimental results will also be a new immune therapeutic targets for breast cancer provides the experimental basis,may be after breast cancer herceptin monoclonal antibody treatment another important discovery,however,about the molecular classification of PD-L1 expression in breast cancer differ and precisely individualized treatment,killing tumor tissues,and the selection of optimal solution to find a balance host drugs and other issues still need to be solved,so further studies are needed to clear.PurposeDiscussing the expression of PD-L1 in breast cancer;The relationship between the type of breast cancer and the expression of PD-L1 protein;Clinical pathologic parameters were associated with PD-L1 protein.Methods225 specimens of breast cancer and 10 cases of adjacent tissues were selected.All specimens were fixed with 10% formalin solution and paraffin embedded.The paraffin blocks were then sectioned and cut into slices with a thickness of 4 μm.Tissue sections were detected by PD-L1 monoclonal antibody using Elivison two-step method of immunohistochemical.The data were used to analyze PD-L1 and its relationship between the clinical indicators of patients by X,2-test,exact probability method,logistics regression analysis and other statistical analysis.ResultsPD-L1 in breast cancer tissue mainly expressed in the cell membrane,and a small amount of expression in the cytoplasm.The positive rate of PD-L1 expression was 12%(27/225)in all cases,and PD-L1 was not detected in the adjacent tissues(0/20).There was no significant difference between the expression of PD-L1 and the age,T stage and menstrual status of the patients(P> 0.05),in metastatic breast cancer patients,the PD-L1 expression was not statistically different from the patient’s metastatic site and metastatic time(P> 0.05),There was significant difference between the expression of PD-L1 and the histopathological grade,molecular typing and metastasis(P <0.05).In metastatic breast cancer patients,the incidence of PD-L1 was higher than the PD-L1(P =0.05).ConclusionThe expression of PD-L1 was detected in breast cancer tissue.PD-L1 was positively correlated with histological grade 3 and Her-2 overexpression of molecular typing,and negatively correlated with Luminal type A of breast cancer.Therefore,PD-L1 may be a predictor of breast cancer progression,and the use of PD-L1 antagonists to block PD-1/PD-L1 pathway may be a new strategy for breast cancer immunotherapy.
Keywords/Search Tags:PD-L1, breast cancer, targeted therapy, molecular typing
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