| Background and Objective: As well known up to now,gastric cancer is one of the most frequent gastrointestinal malignant tumors.According to the statistical analysis data of 2012 GLOBOCAN[1],gastric cancer is the fifth most occurrent malignant tumor worldwide,which ranks second only to lung cancer,breast cancer,colorectal cancer and prostate cancer.More than 70% of the cases occur in developing countries,half of which occur in east Asia.Seriously,gastric cancer was the third leading cause of cancer-related death in China.Furthermore,the death rate is the highest in east Asia.In China,the incidence and mortality of gastric cancer were high,ranking the second and third places in all malignant tumors[2].There were no specific symptoms in the early stage of gastric cancer.When patients visit the clinic,they are often diagnosed with advanced gastric cancer.At present,surgery is still the main treatment for patients with gastric cancer.Although with the continuous improvement of the medical technology level and the deepening understanding of gastric cancer,the operation is more and more standardized,but its overall prognosis is still poor and the overall survival rate is still low.In order to improve the prognosis of patients with gastric cancer,most patients should be combined with chemotherapy,radiotherapy,immunotherapy or other comprehensive treatment methods before or after operation.Before,domestic and foreign scholars focused on the research of pathogenesis and pathology of gastric cancer,and the study of the immune status was less.With the researchers’ understanding of the immune status of gastric cancer,immunotherapy of gastric cancer is gradually emerging worldwide,with a view to further improve the prognosis of patients with gastric cancer.At present,it is believed that the occurrence and development of many malignancies such as gastric cancer are related to immune tolerance and the reduction of anti-tumor immunity.As for the body’s immunity,it can be divided into general immunity and local immunity,while local immunity can more accurately reflect the anti-tumor immunity of the host than the general immunity.At present,the density of dendritic cells(DC),regulatory T cells(Treg),cytotoxic T lymphocytes(GZMB~+CTL),nature killer cells and other immune cells in tumor microenvironment is usually detected to reflect the local immunity of tumor.Alpha-fetoprotein positive gastric cancer(AFP~+GC)is a special type of gastric cancer.Bourreille et al[3] reported it in 1970 for the first time.Subsequently,domestic and foreign scholars began to pay attention to AFP~+GC.According to incomplete statistics,its morbidity approximately accounted for 1.3% to 15% of all patients with gastric cancer,and it was highly aggressive,and can easily transferred to the liver and lymph nodes [4-10].Because of the low incidence of AFP~+GC,the current study on AFP~+GC is mainly reported in the case report.There are few studies on the clinical biological behavior features and local immune status of AFP~+GC.Besides,the existing research is not consistent with the clinical biological behavior of AFP~+GC.The purpose of this study is to analyze and summarize the features of the clinical pathological data of patients with AFP~+GC who received surgical treatment at the affiliated hospital of southwest medical university from December 2013 to December 2017,and to explore its’ clinical biological behavior characteristics and local immunity status.The first part of this study is to explore the clinical biological behavior of AFP~+GC,and the second part is to explore the local immunity of AFP~+GC to further understand AFP~+GC from clinical biological behavior and local immune status,and to provide more theoretical basis for the clinical individualized treatment of AFP~+GC.Methods: With retrospective study applied to this study,we collected the clinicopathological data of patients with primary gastric cancer which were confirmed by pathological examination after surgery in the Department of Gastrointestinal Surgery by using electronic medical record system from December 2013 to December 2017 in the Affiliated Hospital of Southwest Medical University.After excluding liver cirrhosis,hepatitis,pregnancy,germ line embryonal tumor,primary liver cancer and other diseases that may cause alpha-fetoprotein to increase,and according to the serum AFP>10ng/ml,32 cases of AFP~+GC were screened.At the same time,64 patients with alpha-fetoprotein negative gastric cancer(AFP-GC)were randomly selected,who underwent surgery at the corresponding period.We further divided AFP~+GC and AFP-GC by using paraffin blocks of surgical specimen for immunohistochemical staining(S-P method),finally we get 31 cases of AFP~+GC,65 cases of AFP-GC,and 96 cases in total.Then we used paraffin blocks of surgical specimen of the 96 cases to carry out immunohistochemical staining(S-P method).Then,we use S-100 protein antibodies,FOXP3 antibodies,GZMB antibodies individually tagged the dendritic cells,regulatory T cells,cytotoxic lymphocytes and natural killer cells in gastric cancer tissue.The local immune status of gastric cancer patients was measured by counting S-100 protein positive dendritic cells(S-100~+DC),FOXP3 positive regulatory T cells(FOXP3~+Treg),GZMB positive cytotoxic T lymphocytes(GZMB~+CTL)and GZMB positive nature killer cells in the tumor microenvironment of gastric cancer.Results:1.There was significant difference between AFP~+GC and AFP-GC in preoperative CEA content.Compared with AFP-GC,the proportion of patients with preoperative CEA content greater than 6ng/ml was higher in AFP~+GC,and the difference was statistically significant(P<0.05).However,there was no significant difference between AFP~+GC and AFP-GC in gender,age,preoperative pyloric obstruction,preoperative anemia,preoperative albumin content(P>0.05).2.There were significant differences between AFP~+GC and AFP-GC in lymphatic and blood vessel infiltration,depth of invasion,lymph node metastasis,liver metastasis,peritoneal dissemination and TNM staging.Compared with AFP-GC,the proportion of patients with vascular infiltration was higher in AFP~+GC,and the difference was statistically significant(P<0.05).Compared with AFP-GC,the proportion of patients with the infiltration depth of T3/T4 was higher in AFP~+GC,and the difference was statistically significant(P<0.05).Compared with AFP-GC,the proportion of patients with lymph node metastasis was higher in AFP~+GC,and the difference was statistically significant(P<0.05).Compared with AFP-GC,the proportion of patients with liver metastasis was higher in AFP~+GC,and the difference was statistically significant(P<0.05).Compared with AFP-GC,the proportion of patients with peritoneal implantation was higher in AFP~+GC,and the difference was statistically significant(P<0.05).Compared with AFP-GC,the proportion of patients belong to Ⅲ/ Ⅲstage was higher in AFP~+GC,and the difference was statistically significant(P<0.05).However,there was no significant difference between AFP~+GC and AFP-GC in tumor size,tissue differentiation,and nerve infiltration(P>0.05).3.The infiltration amount of S-100~+DC,GZMB~+CTL and GZMB~+NK cells in the tumor microenvironment of AFP~+GC was significantly lower than that of AFP-GC,and the difference was statistically significant(P<0.05).The infiltration of FOXP3~+Treg in the tumor microenvironment of AFP~+GC was significantly higher than that of AFP-GC,and the difference was statistically significant(P<0.05).4.Stratified analysis found that in patients with lymph node metastasis,the infiltration level of S-100~+DC in the tumor microenvironment of AFP~+GC was significantly lower than that of AFP-GC(P<0.05).Regardless of tumor size,Borrmann classification,differentiation,vascular infiltration,nerve infiltration,depth of invasion,liver metastasis,peritoneal dissemination and TNM staging,the infiltration level of S-100~+DC in the tumor microenvironment of AFP~+GC was significantly lower than that of AFP-GC(P<0.05).5.Hierarchical analysis found that in patients of Borrmann type Ⅲ/Ⅲ,of poor differentiation degree,without vascular invasion,without nerve invasion,without liver metastasis,without peritoneal dissemination,of T3/T4 infiltration depth,the infiltration level of GZMB~+CTL and GZMB~+NK cells in the tumor microenvironment of AFP~+GC was significantly lower than that of AFP-GC(P<0.05).Regardless of tumor size,lymph node metastasis and TNM staging,the infiltration level of GZMB~+CTL and GZMB~+NK cells in the tumor microenvironment of AFP~+GC was significantly lower than that of AFP-GC(P<0.05).6.Hierarchical analysis found that in patients without nerve invasion or patients of Ⅲ/ Ⅲstage,the infiltration level of FOXP3~+Treg in the tumor microenvironment of AFP~+GC was significantly higher than that of AFP-GC(P<0.05).Regardless of tumor size,Borrmann classification,differentiation,vascular invasion,depth of invasion,lymph node metastasis,liver metastasis and peritoneal dissemination,the infiltration level of FOXP3~+Treg in the tumor microenvironment of AFP~+GC was significantly higher than that of AFP-GC(P<0.05).Conclusion:1.Compared with AFP-GC,AFP~+GC has different clinical biological behavior.It can easily transfer to the liver and lymph nodes,can easily cause peritoneal dissemination,can easily cause vascular invasion,can cause deeper infiltration level,late stage of pathology and higher CEA level,etc.2.Compared with AFP-GC,AFP~+GC was weaker in the positive immunoregulation capacity represented by S-100~+DC,GZMB~+CTL and GZMB~+NK cells,while the negative immunoregulation capacity represented by FOXP3~+Treg was enhanced.3.The infiltration level of S-100~+DC,FOXP3~+Treg,GZMB~+CTL and GZMB~+NK cells in the tumor microenvironment of AFP~+GC and AFP-GC was related to its biological behavior. |
