| Background:The stomach is one of the most important of the body’s digestive system,stomach once lesions or tumors,the body’s normal function occurs will be seriously affected.Due to differences in reality and stage presence of food hygiene and safety of the Chinese diet,compared with Western countries,the incidence of gastric cancer in our country increased year by year.Among them,the stomach gastric lymphoma has become the second most common cancer after addition of gastric cancer,its incidence continues to rise in recent years,a serious threat to people’s health.PGL(primary gastric lymphoma,PGL)originated gastric diffuse lymphoid tissue,90% of B-cell lymphomas,the most common type of mucosa-associated lymphoid tissue lymphoma,extranodal marginal zone(extranodal marginal zone lymphoma of mucosa-associated tissue,MALT lymphoma)and diffuse large B cell lymphoma(diffuse large B-cell lymphom,DLBCL).Gastric lymphoma is more common in men over 50 years,the lack of specific clinical symptoms,the patient may appear dyspepsia,upper abdominal pain,nausea,vomiting,diarrhea,ulcers,perforations and varying degrees of weight loss,anemia and other symptoms,some patients may not be present any clinical symptoms.Gastric endoscopy can nodular,similar atrophic gastritis,ulcer or performance,hyperplasia,polyps or the like infiltrates,gastric wall thickening seen in rare cases.Primary lymphoma in the stomach of a number of factors,the most widely recognized that gastric lymphoma and Helicobacter pylori infection.A small amount associated with EB virus infection.Since 2016,"the fifth national consensus treatment of Helicobacter pylori infection," published,along with a wide range of applications to improve public health awareness and triple antibiotic,along with HP detection rate has increased,the standard treatment after detection of HP It is widely concerned.With the standard treatment of HP infection,persistent infection of HP my country in recent years a downward trend in the general population,but the incidence of gastric lymphoma has not declined,but increased year by year,in addition to the stomach after gastric cancer has become the second most common malignant tumor.It can be seen in clinical pathological practice,gastric lymphoma has special gastric mucosa microequitment characteristics.A tumor tumor tumor tumor tumor tumor tumor tumor tumor tumor strand b cell lymphoma is shown compared to lymph node B cell lymphoma,showing more complex cell background.In fact,whether it is inert gastric Malt lymphoma or invasive strong gastric DLBCL tumor tissue,a large amount of inflammatory cells can be observed,including lymphocytes,tissue cells,eosinophils,etc.,suggesting gastric lymphoma The occurrence and development is likely to be related to the infiltration of microbritus cells.At the same time,inflammatory factors are another important part of the tumor microenvironment.The rich lymphoid pulverar cells in the gastric lymphoma tumor microenvironment provide immunological foundation for inflammatory factors.Studies have shown that inflammatory factors and tumor cell proliferation,genomic instability,vascular production,anti-apoptosis,tumor invasion,and metastasis relations,tumor microenvironment The role of inflammatory factors on tumors depends on tumors in immunomotrack monitoring,immune editing,immune treatment or The immune escape is different from the middle stage.Therefore,the distribution characteristics of inflammatory cells and inflammatory factors of tumor microenvironment in gastrointestinal lymphoma are explored.At the same time,endoscopic examination of gastrointestinal diseases is the preferred inspection item for the screening and diagnosis of gastrointestinal diseases in China ’s social common population.In recent years,with the expansion of ultrasound technology in clinical applications,ultrasonic endoscopic(EUS)emerges,EUS-assisted digestive endoscopy has greatly improved the positive rate of endoscopic diagnosis.The domestic department of our hospital is a national key discipline.The diagnosis of gastric lymphoma is large,and the diagnosis of gastric lymphoma is basically depends on the pathological biopsy of ultrasonic endoscopic.It combines patients to diagnose patients through pathological form.Basically constitute pathological diagnostic modes of current gastric lymphoma.However,as the main type of gastric lymphoma,the gastric Malt lymphoma and DLBCl still have great challenges in the diagnosis of the inner mirror small specimen biopsy,and the treatment plan and clinical prognosis are very different,do a good job in diagnosis and identification.It is critical to find more differential diagnostic means with important clinical guidance.Therefore,the distribution characteristics of inflammatory cells and inflammatory factor in tumor microenvironment in gastric lymphoma is to investigate the new direction of different types of diagnosis,differential diagnosis and prognosis assessment of gastric lymphoma.Therefore,this study collects the systematic observation of the 127-story labeling of gastric lymphoma in our hospital.It adopts morphological observation,immunozyme dyeing,immunohistochemical system to detect the true situation of HP and EBV infection in gastric lymphoma,re-evaluate infection Factors in the development of gastric lymphoma,comprehensive analysis of the distribution characteristics and polarization ratio of immune cells in gastric lymphoma microenvironments,and conduct parallel controls with chronic gastritis in the same period,further assessing gastric lymphoma microenvironment T cells,macrophages The expression and distribution of relevance inflammatory factors IL-17,IL-23 and IFN-γ,the system understands the distribution and characteristics of gastric lymphoma microenvironmental inflammatory factors.Inquiry immune cells,inflammatory inflammation factors,etc.,in chronic gastritis,gastric lymphoma,auxiliary diagnosis and differential diagnosis,prognosis evaluation,and provide tumor micro-environmental assessment for clinical practice.Purposes:1.The purpose of this study is to systematically detect the real situation of HP and EBV infection in gastric lymphoma,re-evaluate the weight of infection factors in the occurrence and development of gastric lymphoma,and objectively analyze the infection situation of HP and EBV in gastric lymphoma without the interference of methodological factors.2.The relative percentage of CD4+T cells,CD8+T cells,CD68+ macrophages and CD163+ macrophages in gastric lymphoma microenvironment,and the polarization ratio of immune cells of CD4/CD8 and CD68/CD163 were systematically evaluated,and compared with chronic gastritis in the same period.To explore the role of immune cells in the transformation between chronic gastritis and gastric lymphoma,and the value of auxiliary diagnosis,differential diagnosis and prognosis evaluation.3.To analyze the expression and distribution of T cell-related inflammatory factors IL-17 and IL-23 IFN-γ in gastric lymphoma microenvironment,and compare them with chronic gastritis in the same period,so as to systematically understand the distribution and characteristics of inflammatory factors in gastric lymphoma microenvironment.To reveal the significance of inflammatory factors in microenvironment of gastric lymphoma in auxiliary diagnosis,differential diagnosis and prognosis evaluation.Methods:1.A total of 138 gastric lymphoma specimens diagnosed by gastroscopy and partial gastric/total evaluation resection from January 2015 to December 2018 in the First Affiliated Hospital of Naval Military Medical University were collected,including 98 gastroscopy specimens and 40 gastric partial/total resection specimens,including 83 cases of DLBCL83 and 44 cases of MALT lymphoma,with a total of 127 cases included in the study group.45 cases of chronic gastritis diagnosed at the same time were taken as control group.2.Detection of HP and EBV: Basic fuchsin staining,methylene blue staining and HP immunohistochemical staining were used to observe HP infection in gastric lymphoma.EBER in situ hybridization was used to detect EBV infection in gastric lymphoma.3.Immunocytoassessment: Immunohistochemical staining of CD4+ and CD8+T cells to assess the proportion of T lymphocytes in gastric lymphoma and chronic gastritis microenvironment.Immunohistochemical staining of CD68+ and CD163+ macrophages was used to evaluate the proportion and polarization state of macrophages in gastric lymphoma and chronic gastritis microenvironment.4.Expression of inflammatory factors: Immunohistochemical staining of IL-17,IL-23 and INF-γ was used to evaluate the expression and distribution of T cell-related inflammatory factors in gastric lymphoma and chronic gastritis.5.Results Interpretation and statistical analysis: Image J software developed by National Institutes of Health was used for cell counting.All data were analyzed by SPSS25.0.All data are expressed with median interquartile spacing.For the measurement data conforming to normal distribution,T test is used for comparison between the two groups,and nonparametric test is used for the measurement data not conforming to normal distribution.p<0.05 is statistically significant.Results:1.Detection of infection factors of gastric lymphoma;(1)(1)HP infection in gastric lymphoma is lower than that reported in literature: HP infection is still the main infection factor of gastric lymphoma,after excluding the influence of methodology and subjective factors on the observation of HP detection results.This study found that the positive rate of gastric lymphoma was 46%,which was lower than 60-80% reported in literature.It is suggested that the role of non-infection related factors other than HP in the occurrence and development of gastric lymphoma deserves further attention.(2)The infection rate of EBV in gastric lymphoma is low:: After excluding the influence of methodology and subjective factors,the results show that the positive rate of EBER in gastric lymphoma is only 7.90%,and all of them are DLBCL,which is similar to previous literature reports,suggesting that EBV has little relationship with the occurrence of gastric lymphoma.2.Analysis of immune cells in gastric lymphoma microenvironment;(1)(1)The distribution of immune cells in gastric lymphoma is characteristic: CD4+T cells are dominant in the inflammatory microenvironment of gastric lymphoma.The relative percentage of CD4+T cells in gastric MALT lymphoma was higher than that in DLBCL(P=0.048),while the relative percentage of CD8+T cells had no significant difference(P>0.05).The ratio of CD4/CD8 in MALT lymphoma was significantly higher than that in DLBCL group(P=0.038).(2)The distribution of macrophages in gastric lymphomas is characteristic: the relative percentage of macrophages in gastric DLBCL is higher than that in gastric MALT lymphoma,which correlates somewhat with the more aggressive nature of gastric DLBCL observed morphologically.The difference in the distribution of macrophages in the tumor microenvironment between gastric DLBCL and MALT lymphoma is statistically significant,and the relative percentage of macrophages in the tumor tissue of gastric DLBCL is greater than that of malt Lymphoma Group;the relative percentages of CD68 +,CD163 + macrophages,and the CD68 / CD163 ratio were greater than those of the MALT lymphoma group(P < 0.05).(3)Differences in immune cells among gastric lymphomas can be used in daily diagnostics with differential diagnosis as follows: propensity to diagnose MALT lymphoma when the relative percentage of background CD4 + T cells is ≥ 5%,propensity to diagnose DLBCL when the relative percentage of CD4 + T cells is < 5%,propensity to diagnose DLBCL when CD4 / CD8 is < 10,and propensity to diagnose MALT lymphoma when the relative percentage of CD163 + macrophages is > 2.5Lbcl,MALT lymphoma tends to be diagnosed when the relative percentage of CD163 +macrophages is ≤ 2.5.(4)Immune cell differences in gastric lymphoma may be used to aid in prognostic assessment: the relative percentage of CD163 + macrophages in the neoplastic stroma of gastric DLBCL > median patients have a worse prognosis.3.Analysis of inflammatory factors in inflammatory microenvironment of gastric lymphoma;(1)The expression of inflammatory factors in gastric lymphoma microenvironment is characteristic: in gastric lymphoma,both interstitial lymphocytes and tumor cells can secrete cytokines.Compared with MALT lymphoma group,the score of IL-17 in stomach DLBCL tumor tissue is higher than MALT lymphoma,but the score of IL-23 in tumor tissue has no significant difference.IFN-γ was only expressed in the residual gastric mucosa adjacent to tumor.(2)The microenvironment inflammatory factors of gastric lymphoma have little correlation with prognosis,and the prognosis of gastric lymphoma has little correlation with IL-17 and IL-23 scores.The prognosis of gastric DLBCL is related to the IL-17 score of tumor tissue.The prognosis of patients with IL-17 score ≤5 is obviously better than that of patients with IL-17 score > 5.(3)Interaction between immune cells and inflammatory factors in gastric lymphoma microenvironment: In gastric lymphoma,tumor B cells and CD68+ macrophages secrete a large amount of IL-23,which further promotes CD4+T cells to proliferate and differentiate into Th17 cells which can secrete IL-17.Th17 cells secrete a large amount of IL-17,which further activates NF-κB,MAPK and other signal pathways,and promotes the proliferation and invasiveness of small blood vessels in tumor tissues.Conclusions:(1)HP infection rate of gastric lymphoma is lower than that of previous studies.Non-infectious factors are worthy of attention in further study of gastric lymphoma microenvironment.(2)Gastric DLBCL has more obvious microenvironmental differences compared with MALT lymphoma,and the most distinct point of immune cells in the microenvironment of DLBCL versus MALT lymphoma is that the immune cell distribution profile is different from the polarization ratio.This difference can be used to assist clinical diagnosis with differential diagnosis and help judge prognosis evaluation in clinical extension applications.(3)The inflammatory microenvironment of gastric lymphoma is closely related to inflammatory factors,and the interaction between inflammatory factors and immune cells plays an important role in the occurrence and development of cancer.Gastric lymphoma itself is a b-cell derived tumor,and the source and mechanism of inflammatory factors are more complicated than those of ordinary tumors.Therefore,in the inflammatory microenvironment of gastric lymphoma,the role of inflammatory factors including IL-17,IL-23 and IFN-γ in tumorigenesis and development,and the correlation with the prognosis of patients need to be further studied. |
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