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Relationship Of Epidermal Growth Factor Receptor Expression With Clinical Symptoms And Metastasis Of Invasive Breast Cancer

Posted on:2020-10-06Degree:MasterType:Thesis
Country:ChinaCandidate:L H HanFull Text:PDF
GTID:2404330575451579Subject:General surgery
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Background and objective Breast cancer,characterized by high heterogeneity in terms of its etiology and pathology,is the most frequently occurring cancer in women and poses a serious healthy menace,with an increasing tendency of morbidity.There are 1.3 million new cases in 2008 worldwide.However,1.7 million new cases of breast cancer or 25% of all female cancers were diagnosed according to GLOBOCAN statistics for 2012.In China,breast cancer has ranked second in the incidence of malignant tumors,ranked first in female malignant tumors and seriously threatened the health of women.Current managements of breast cancer containing diagnosis and treatment have rapidly progressed into the molecular era.Molecularly targeted therapy of breast cancer is also integrated into other treatments,such as surgery,chemo-therapy,radiotherapy,hormone therapy,and anticancer drugs.As breast cancer-related molecules,estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER2),have defined prognosis and identified tumors for targeted therapy for decades,the underlying molecular mechanisms of breast cancer are complicated and remain unknown,and there are other highly specific molecules involved in its occurrence and development.Previous studies have shown that high expression of epidermal growth factor receptor(EGFR)occurs in many tumor diseases,such as breast cancer,head and neck cancer,ovarian cancer,bladder cancer,and kidney cancer.It is suggested that ubiquitin-specific peptidase 18 could promote breast cancer growth by up-regulating EGFR and activating the AKT/Skp2 pathway,which indicated that EGFR was involved in occurrence and development of breast cancer.Thus,this research tried to analyze and explore the role of EGFR in the clinical symptom and metastasis of patients with invasive breast cancer(IBC)through retrospective analysis of about 189 patients with IBC.Methods 1.A total of 189 patients with IBC admitted to our hospital from January 2014 to June 2017 were selected in this research.The age of patients was 36–69 years.Pathological data of all patients were collected,including tumor size,patients' age,lymph node metastasis condition,clinical stages,conditions of recurrence,and metastasis.2.Immunohistochemistry was carried out on paraffin-embedded tumor tissue by using SP immunohistochemistry kit and DAB chromogenic kit.Staining for EGFR was performed on 5-mm-thick sections with the rabbit antihuman EGFR monoclonal antibody.After sections were deparaffinized,rehydrated,and incubated in 3% H2O2 to block endogenous peroxidase activity,all sections were placed into sodium citrate buffer(0.01 M,p H 6.0)and boiled in a microwave oven for antigen retrieval.To block nonspecific binding,the sections were incubated in 5% bovine serum albuminat 37°C for 30 min.Then the sections were incubated overnight with the rabbit antihuman EGFR monoclonal antibody(1:50).After rewarming at 37°C for 30 min,the sections were incubated with the goat antirabbit Ig G(1:100)for 30 min at 37°C,and the immunoreactions were visualized using DAB.In the end,the sections were counterstained with hematoxylin,dehydrated,and covered with cover slips.Images were observed using an automatic microscope 3.Total protein in the IBC tissues was isolated using a total protein extraction kit.Protein concentration was determined using the bicinchoninic acid assay following the standard protocol.Protein samples(50 mg)were resolved by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis and transferred to polyvinylidene fluoride membranes.Membranes were then blocked and incubated overnight with the primary antibody,anti-rabbit EGFR(1:500;),anti-rabbit b-actin(1:1,000),and subsequently incubated with horseradish peroxidase-linked goat anti-rabbit Ig G secondary antibody(1:5,000).Band intensities were quantified using Quantity One software and normalized to b-actin.4.SPSS 21.0 software and chi-square test were used to analyze the relationship between the expression of EGFR and clinicopathological parameters in breast cancer tissues and paratumor breast tissues.When P < 0.05,the difference was statistically significant,and there was a significant difference at P < 0.01.Results The results of statistical analysis showed that the positive expression of EGFR in IBC(140/189 = 74.07%)was significantly higher than that of paratumor breast tissues(23/189 = 12.16%)(P < 0.01).There was no significant correlation between the expression of EGFR and patients' onset age as well as menopausal status(P > 0.05),but it was significantly correlated with the diameter of tumor mass,lymph node metastasis,TNM staging,and histological gradation(P < 0.05).The positive expression of EGFR in estrogen receptor(ER)-negative group(64 tissues,84.2%)was significantly higher than that in ER-positive group(76 tissues,67.3%)(P < 0.05).There was no significant difference in the positive expression of EGFR between progesterone receptor(PR)-positive group(73 tissues,73.0%)and PR-negative group(67 tissues,75.3%)(P > 0.05).The positive expression of EGFR in human epidermal growth factor receptor 2(HER2)-positive group(67 tissues,84.8%)was significantly higher than that in HER2-negative group(73 tissues,66.4%),with a significant difference(P < 0.05).Conclusion The high expression of EGFR can be used to predict the severity of IBC,as well as the candidate biomarkers of metastasis,and it may also be associated with poor prognosis of IBC patients.
Keywords/Search Tags:epidermal growth factor receptor, invasive breast cancer, positive expression, paratumor breast tissues
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