| Objective:By observing the expression of HER-2 in patients with advanced gastric cancer between different individuals and before and after surgery,as well as between primary and metastatic foci,and in different regions of the primary tumor in the same individual.Objective to analyze the effect of temporal and spatial heterogeneity of tumor on the over expression of HER-2 in patients with advanced gastric cancer.In order to provide theoretical basis for further study on the accurate and individualized treatment of gastric cancer.Method:A total of 521 patients with adenocarcinoma of the stomach or gastroesophageal junction were collected from prospective,multicenter,open,randomized controlled phase III clinical trials(NCT01516944).Among them,277 patients were operated on directly,and the other patients were treated with neoadjuvant chemotherapy(n = 244).Immunohistochemical staining(IHC)method,the direct operation of 277 cases of advanced gastric cancer patients after operation to detect the expression of HER-2(2+ and 3+ is that the overexpression of HER-2 protein).To analyze the effect of tumor heterogeneity on the over expression of HER-2 protein in different stages of patients with advanced gastric cancer.To observe the expression of HER-2 in patients with advanced gastric cancer before and after chemotherapy,before and after chemotherapy,and to analyze the effect of HER-2 on tumor heterogeneity.Observation of patients with advanced gastric cancer primary tumor and metastasis(lymph node metastasis,liver metastasis,peritoneal exfoliated cells(PLC)positive expression of HER-2 in different areas of the state),the primary focus of the analysis of the effect of tumor heterogeneity on HER-2 expression of advanced gastric cancer patients.Result:1 277 cases of surgery patients,HER-2 expression and the age and sex of patients,tumor size,distant metastasis,vascular invasion,neural invasion had no statistical difference(P>0.05),and degree of differentiation,with Lauren type,depth of invasion,lymph node metastasis and TNM stage had statistical differences(P<0.05).2 277 cases of surgery patients,preoperative and postoperative biopsies specimens tested for HER-2 protein IHC,gastroscope bite the tissues examined HER-2 expression rate was 32.85%,over expression rate of 29.60%specimens measured HER-2 protein after operation,although in the preoperative and postoperative specimens specimens in two groups,HER-2score 0/ 1+ and 2+/3+ two group was very similar,but 41 cases(14.8%)paired samples IHC score inconsistent(biopsy score of 0/1+ in surgical specimens,score 2+/3+ score for 2+/3+ or biopsy specimens in surgical specimens,score0/1+).3 244 patients who received neoadjuvant chemotherapy,after neoadjuvant chemotherapy,15 cases were removed after chemotherapy in patients with gastroscope biopsy specimens for pathological bite of inflammatory tissue or atypical cells,in the remaining 229 patients,104 patients had chemotherapy before gastroscopy examination of the expression of bite HER-2,expression rate of HER-2 was 45.41%,86 patients with over expression of HER-2 after chemotherapy endoscopy biopsies,over expression rate is 37.55%.Although in the chemotherapy before and after endoscopic biopsies,HER-2 score of 0/1+ and 2+/3+ two group was very similar,but 26cases(11.35%)paired samples IHC score before chemotherapy were inconsistent(score of 0/1+ in the samples after chemotherapy or chemotherapy before the score 2+/3+ score was 2+/3+ in specimens of specimens after treatment then the score for 0/1+).4 30 cases of left supraclavicular lymph node metastasis,the primary tumor and lymph node HER-2 expression concordance rate was 86.67%.The odds ratio was 13.33%(4/30).4 cases of inconsistent expression of protein.Of which 2 cases of primary tumor and lymph node negative,overexpression of tumor HER-2 protein transfer(positive change),positive change rate was6.67%;of which 2 cases of primary tumor and metastatic lymph node positive,HER-2 negative expression(negative change),negative conversion rate was6.67%.The agreement of HER-2 protein expression in 12 cases of patients with positive liver biopsy was,and the inconsistency rate was: 16.67%(2/12).2 cases of inconsistent expression of protein.Of which 1 cases of primary liver metastases and negative HER-2 protein expression(positive change),positive change rate was 8.34%;of which 1 cases of primary tumor and liver metastasis positive and negative expression of HER-2 protein(negative change),negative conversion rate was 8.34%.In 5 cases of peritoneal lavage fluid exfoliative cells(PLC)positive patients,the consistency of HER-2protein expression between the newly diagnosed gastroscope biopsy and peritoneal lavage fluid was,and the inconsistency rate was: 60%(3/5).3 cases of inconsistent expression of protein.3 cases were positive,but HER-2 protein was negative(negative)in peritoneal lavage fluid.5 The same individual,244 patients who received neoadjuvant chemotherapy,after neoadjuvant chemotherapy,no specimens from 10 cases of patients with postoperative residual carcinoma(PCR after chemotherapy),the remaining 234 patients,the expression of HER-2 protein after operation(+)of about 86 people,over expression rate of about 36.75%.The difference was not statistically significant(P=0.166>0.05)(45.41%)compared with that before chemotherapy.Although the specimen before chemotherapy and postoperative endoscopic biopsies,HER-2 score of 0/1+ and 2+/3+ two group was very similar,before chemotherapy endoscopy biopsies specimens of HER-2(+)and(+)protein after a total of 76 people,before chemotherapy endoscopy biopsies specimens of HER-2 protein(-)and postoperative(co-)118,the consistency is 82.90%.However,the IHC scores of 40 patients(17.47%)were not consistent(the score of 0/1+ before chemotherapy was0/1+ after chemotherapy,the score was 2+/3+,and the score of 2+/3+ before chemotherapy was higher than that before chemotherapy.6 50 cases of surgery patients,patients with primary tumor of the same in different regions for coarse needle puncture and IHC method to detect the expression of cardiac,side and center,pyloric side three HER-2 protein consistent rate was 86%(43/50).About 14% of the IHC scores were inconsistent.In 7 patients,there was negative and over expression in the primary tumor.Conclusion:1 In the different individuals,with the depth of tumor invasion,lymph node metastasis,TNM staging increased,HER-2 protein overexpression rate increased,and the expression of HER-2 protein in the differentiation rate of gastric cancer patients in a larger proportion..2 In the same individual,preoperative and postoperative chemotherapy before and after chemotherapy,the expression of HER-2 in high consistency,but due to the tumor effect of temporal heterogeneity,comprehensive preoperative and postoperative chemotherapy before and after chemotherapy in patients with positive,can improve the positive rate of HER-2.3 HER-2 expression in liver metastasis and lymph node metastasis and peritoneal lavage fluid exfoliated cells in the HER-2 state has a spatial heterogeneity of the tumor,if the primary HER-2 negative,should be further detection of metastases.4 In 50 cases of gastric carcinoma,the expression of HER-2 was different in different regions of the same lesion.The results showed that the positive rate of HER-2 was related to the number of sites and the number of samples.Due to the spatial heterogeneity of tumor,the increase of tumor detection area would be helpful to evaluate the expression of HER-2. |
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