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The Expression And Significance Of HER2 In Primary Gastric Cancer And Corresponding Metastatic Lymph Nodes

Posted on:2016-06-16Degree:MasterType:Thesis
Country:ChinaCandidate:D X YangFull Text:PDF
GTID:2284330461469803Subject:Surgery
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Background and Objective:Malignant tumor is one of the most important cause of human death, and the stomach cancer is the second high fatality rate in the world.Evidence from the American cancer society suggests that the world in 2007, about 7.6 million people die for malignant tumor, about 12.3 million were new cases, currently was about 45 million human cancer cases.Cancer has become the first leading cause of death in the developed countries, and accounting for 21.6% of the deaths.In 2010, the world will be more than 8 million people died for cancer, that instead of cardiovascular disease (CVD) to become the world’s deadliest diseases.According to 2011 statistics, in our country each year has about one hundred and ninety thousand new cases of gastric cancer patients[1], also is the third higher, after lung cancer and liver cancer deaths causes, each year about two hundred thousand people have died of stomach cancer. Benefit of the tumor knowledge propaganda and the popularization of gastroscope examination such as the implementation of the positive coping strategies, it had decline trend in mortality in recent years.However, on the treatment strategy, progress is still slowly. Patients with early gastric cancer’s treatment result is good, but the early diagnosis it is difficult, but patients with advanced gastric cancer survival rates are low, part of the reason may be due to its effective inspection strategy is limited, often at the time of diagnosis was late stage, and for the treatment of patients with advanced cancer solutions is limited, so the prognosis is poor, the implementation of standardized treatment of stage I cancer of the stomach 5-year survival rate is 82-95%, II period was 55%, III period is 15-30%, while IV period is only 2%[2].How to deal with the situation as a problem in medical research.In recent years, along with the advance of science and technology and the further understanding the mechanism of cancer, the study of tumor also go deep into the cellular, molecular and gene level, and even some involved in cell differentiation, proliferation and migration of genetic and molecular mechanisms also have been found and understood treatment mode have been found and the application gradually.On the treatment of cancer, surgery and chemical drug treatment and radiation results had some changed than the previous, but progress has been slow.Targeted therapy has become the new one of hotspots researches in recent years, human epidermal growth factor receptor 2 (HER-2) gene and protein expression has become one of the hot spot of research on molecular targeted therapy.HER-2/ neu is the human epidermal growth factor receptor’s (epidermal growth factor receptor, EGFR) second member of the family, EGFR family members include HER-1, HER-2, HER-3, HER-4, often expressed in a variety of epithelial origin tumors,such as breast cancer,bladder cancer, ovarian cancer, gastric cancer[3], lung adenocarcinoma, the expression rate is about 0.4%- 12.4%, it involves those tumor’s occurrence, development process. Part of the study also hints that it also involves tumor’s invasive and metastatic. In breast cancer, HER-2 expression rate is about 25% of the patients, and about molecular target therapy for patients with breast cancer treatment and prognosis[4].As it expressed in bladder cancer rate is about 12.4%, and its role in the tumor and the treatment of guiding significance to need to be further research.In gastric cancer, a large number of studies have shown that in gastric cancer HER-2 expression rate is about 3.9%- 51.1%, on average about expressed in 16.4% of patients with gastric cancer, it play a impotant role in gastric cancer occurrence and development,is adverse prognostic factor in patients with gastric cancer[3,5].By bead sheet resistance as a recombinant DNA derived humanized monoclonal antibodies, it can be selectively and human epidermal growth factor receptor 2 (HER-2) outside of the cell phase effect, antitumor effect.In addition, in the stomach cancer strains have higher expression rate of HER-2[6], and gastric cancer in vitro and in vivo preclinical model, according to the data by bead sheet resistance in combination of platinum and fluorine pyrimidine drugs against its HER-2 targets of therapy has a significant anti-tumor effect, that can improve the patients’ overall survival rate and mortality risk[7].Based on this result, at foreign countries, in 2010,Drug Administration in Europe and the United States food and drug administration (FDA) has approved a combination of chemotherapy treatment by target therapy of HER2 positive patients with stomach and the stomach- esophagus junction cancer.At home, after medical workers unremitting efforts, in 2011, HER-2 expert group of gastric cancer HER-2 testing guidelines issued, normal the gastric cancer detection and scoring criteria, provides reference for the analysis of HER-2 in cancer of the stomach.In 2013, has published a consensus HER-2 positive advanced gastric cancer molecular targeted therapy, It also recommend positive HER-2 expression are considered in the treatment of patients with molecular targeted therapy.At present, in our country, the more is when the patient is sick in the lymph nodes or distant metastasis of the advanced-state,Reason for patients with HER-2 positive research focused on the related research of gastric cancer primary focal more, for the corresponding research in lymph node metastases is less, especially,the HER-2 negative in gastric cancer primary tumors of patients,but with lymph node metastasis positive, its expression in the lymph node metastases of less research,About the lymph node metastases of HER-2 expression level, and the clinical pathological parameters, targeted therapy and prognosis of patients with the results of the study is no unified conclusion.This study by immunohistochemistry (IHC) method to detect its HER-2 expression in patients with gastric cancer, to explore its HER-2 and the prognosis of patients with gastric cancer, and the relationship between them, in order to provide more clinical basis for gastric cancer targeted therapy.This experiment by immunohistochemical S-P method to detect HER-2 in stomach tumor tissue, cut edge expression levels in the organization, and analysis HER-2 expression and gastric cancer patients with the relationship between the clinical pathologic factors, to explore the diagnosis and treatment of gastric cancer, the role of the judge and prognosis of malignant degree.Methods:We Selecte 60 clinical cases in July 2013 to July 2014, luzhou medical school affiliated hospital gastrointestinal surgery R0 resection surgery, and postoperative pathological examination confirmed that have lymph node metastasis of gastric carcinoma,A11 patients with complete clinical data without any preoperative radiotherapy, chemotherapy and other adjuvant treatment history,Surgical removal of the specimen with intact tumor tissue and cut edge normal tissue. Selected tumor tissue and cut edge normal tissues and lymph nodes metastases specimens each 60 cases, all specimens were confirmed by pathological examination.Using immunohistochemical S-P method to detect HER-2 expression level in the area of primary gastric cancer and lymph node metastases, the detection of lymph node metastases, we will analyze the cases of metastases,to test all specimens or detect HER-2 positive so far.Result analysis, expression level of the 60 cases of gastric cancer primary tumors and cut edge normal tissue specimens and lymph node metastases in the sample comparison, analysis of primary tumors and lymph node metastases of HER-2 and gastric cancer in patients with clinical pathological factors,and the relationship between primary tumors and lymph node metastases with the correlation of HER-2 expression will be analyzed.Result:1. HER-2 expression rate in the primary site of gastric cancer was 21.67% (13/60), in the cut edge is no expression in normal tissue (0/60), the positive expression rate have obvious difference, that has no statistical significance (P< 0.05).Positive expression of HER-2 in primary gastric cancer tissue and the patient’s gender, age, tumor location, degree of differentiation has no significant difference (P> 0.05), and TNM stage of the tumor, tissue infiltration depth has a statistical difference (P< 0.05).2. The expression of HER-2 in the corresponding lymph node metastases (positive) express rate is 18.33% (11/60).HER-2 in the corresponding positive expression rate of lymph node metastases in cancer tissue with the patient’s gender, age, degree of tumor differentiation has no statistical difference (P> 0.05), and TNM stage of the tumor, the part of the cancer tissue and cancer tissue infiltration depth has statistically difference (P< 0.05).3. In 60 gastric cancer cases tissue and lymph node metastases tissues:primary tumors and lymph node metastases are positive for a total of 6 cases of HER-2 expression,Primary tumors were positive for the expression of HER-2 in cancer tissue and corresponding lymph node metastasis carcinoma tissue HER-2 expression appears in a total of 7 cases of negative;The primary focal HER-2 present negative expression in cancer tissue and corresponding lymph node metastasis carcinoma tissue is positive HER-2 expression in 5 cases.4. HER-2 over expression in gastric cancer primary carcinoma tissues and in corresponding lymph node metastasis carcinoma tissue has no statistical difference (P> 0.05).Conclusion:1. In sichuan yunnan and guizhou fringe areas,In gastric cancer patients,The positivity of HER-2 expression rate has similar result with reported at home and abroad;This study shows that the expression of HER-2 may mainly associated with tumor progression, but not play a major role in the eraly stage of tumor, in addition,the expression of HER-2 have not clearly correlation with location, age, gender, tissue differentiation degree.2. The positivity of HER-2 expression in Gastric cancer metastasis lymph node has more closely relationship with tumor primary site (stomach bottom/cardia), tumor infiltration depth and TNM staging.In addition, HER-2 expression in primary focal and lymph node metastases in gastric cancer have heterogeneity, upper location gastric cancer metastasis lymph node in the patients and under the age of 60 have higher positive rate, that hint this part of patients with positivity of HER-2 expression gastric cancer cells have a higher potential of lymph node metastasis.Part of the patients (HER-2 expression of gastric cancer is negative, and expression of HER-2 in lymph node metastases is positive), could bring into Trastuzumab treatment, Therefore, detection HER-2 expression of lymph node metastases at the same time can be a effective supplement to original site testing.
Keywords/Search Tags:gastric cancer, HER-2 over-expression
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