| Background and Objective:Gastric carcinoma is the most common malignant tumor. The development of gastric carcinoma is a multi-factor process. It is generally accepted that the development of gastric carcinoma progresses from chronic gastritis to gastric atrophy, intestinal metaplasia, dysplasia and invasive carcinoma. Cell-mediated immunity is the main-mechanism of anti-tumor immunity of the host. Activated CTL cell and NK cell play an important role in the cell-mediated immunity. CTLs use the perforin/granzyme and Fas/Fas ligand (Fas/FasL) pathways to induce cytotoxicity of target cells. The perforin/granzyme pathway is often thought to play the predominant role. GrB is the most abundant granzymes and is the fastest effector which is contained in CTLs with perfoin. They are the characteristic marks of CLs. GrB+ and PFP+ lymphocytes were further characterized into their subsets including CD4+ T cells, CD8+ T cells, NK cells, so the density of their in tumor infiltrating directly reflect the local immune status.The study at home and abroad in recent years found that GrB and PFP not only expressed in CTL and NK cells, but also found in others cells, and they particularly were also found in tumor cells. The expression of GrB and PFP were not only found in lymphoma, but also were found in epithelial cancer such as breast cancer and lung cancer. The lately report that GrB in benign and malignant gastric tissues was expressed, and the expression of GrB in gastric cancer may be related to local immune suppression. If GrB+ gastric cancer cells have cytotoxic lymphocytes of the biological characteristics, it is unknown. The expression of PFP is if or not correspond to GrB expression in gastric cancer cells, which have not yet been reported, and the significance of their expression in gastric cancer remains unclear. In recent years, studies have shown that gastric cancer can be derived from bone marrow-derived cells (BMDC), which presented a new theory of non-epithelial origin. BMDC has strong plasticity, not only differentiated cells by themselves, but also produce other cell differentiation and functional role of the daughter cells, they most likely have a differentiated phenotype of lymphoid tissue.Base on our previous studies, we expect to explore the expression of GrB and PFP in gastric cancer and the relationship between local immune status. This dissertation was composed of two parts:In Part I, we arm to investigate if the expression and distribution of GrB corresponding to PFP in gastric cancer, and then the gastric cancer cells have the characteristics of cytotoxic lymphocyte phenotype and function. It may be provides a strong evidence of non-epithelial origin theory for GrB-positive gastric cancer, and it also may provide an objective basis for the establishment of a new subtype for gastric cancer. In Partâ…¡, we expect to evaluate the relationship of the PFP+ TIL cell density and local immune status in gastric cancer.The connection of PFP+ tumor infiltrating lymphocytes (tumor infiltrating lymphocyte, TIL) density in gastric cancer to clinicopathologic features. Methods:Thirty-five cases specimens of gastric cancer were collected at random. None of the patients had received radiotherapy,chemotherapy and Immunotherapy before operation.By immunochemical PV method, the expression of GrB and PFP were detected in 35 cases of gastric cancer, cancer-adjacent tissues,Surgical margin and the corresponding lymph node tissue. And then counts the density of GrB+ TIL cells and PFP+ TILcells infiltration in Surgical-margin, their cancer-adjacent tissues and gastric cancer. Result: Part I,1,GrB protein were expressed in peripheral tissues of gastric cancer, gastric resection marginand and cancer tissue.the positive rate was40.00%(14/35),42.86%(15/35),48.57%(17/35), Every two has no significant difference(P>0.05),Synchronous detection of the PPF in gastric margin,adjacent carcinoma and metastatic lymph tissue.PFP+ TIL cell are scattered instroma of different parts of the stomach tissue, can be used as an internal positive control. GrB+ and GrB- gastric cancer corresponding to peripheral tissues, the expression of adjacent tissues GrB significant difference.2, GrB expression in gastric cancer was no significant difference in age level, histological grade, depth of invasion and TNM stage (P>0.05).but was significantly different in Sex, lymph node metastasis(P<0.05).3, GrB in the lymph node metastasis was also expressed in gastric cancer cells,35 patients with gastric cancer in a total of 23 patients with lymph node metastasis, GrB lymph node metastasis in gastric carcinoma was 52.2%(12/23). The corresponding GrB expression in primary foci was 26.1%(6/23), no significant difference between the two, (P> 0.05). Partâ…¡, 1,PFP+ TIL cells can be seen in varying degrees of interstitial infiltration in different gastric tissue. Margin compared with the adjacent (P<0.01); cancer tissue compared with adjacent (P < 0.01); cutting edge of cancer compared with cancer tissue (P< 0.05). 2, The infiltration density of PFP+ TIL cell around gastric cancer had a significant difference in the depth of invasion, lymph node metastasis, TNM, (P<0.05).Conclusion:According to the current results, GrB posi-tive gastric cancer cells do not express PFP together, non-dependent on the PFP expression in gastric, which failed to confirm that GrB-positive gastric cancer cell phenotype with lymphatic characteristics. So the non-epithelial origin for the doctrine of gastric cancer (BMDC origin) not yet mentioned Strong support.This need a large of sample sizes for further research.GrB maybe participate in the GrB+ gastric cancer of whole process.It maybe the early phenomenon in the GrB+ gastric cancer, but the specific mechanical need the further investigate.PFP+TIL cells in adjacent cancer significantly higher than the density of cancer nest, suggesting that gastric partial PFP+ TIL cells decreased, decreased local immunity, contribute to tumor growth and metastasis. PFP+ TIL cells in tumor density and prognosis of interstitial infiltration may be positively related to the prognosis of patients with high density may be better, but the specific mechanism needs further clarified.
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