| ObjectiveTo evaluate the impacts of tumor infiltrating immune cells on long-term survivals of gastric cardia carcinoma and the significances of Transforming Growth Factor-β1(TGF-β1) in the interaction between immune system and tumor.MethodsFrom October 2000 to October 2002, 137 patients with gastric cardia carcinoma underwent curative resection in Shantou University, Medical College, Cancer hospital. All patients were followed-up for at least 5 years. Detailed clinical and pathological data were collected. Intratumoral and peritumoral presence of various tumor-infiltrating immune cells, including CD3+,CD8+,CD68+,CD20+ cell, as well as the expression of tumor-deriving TGF-β1 were detected using immunohistochemistry in resection specimens from 133 patients(4 cases who died from severe surgical complications were excluded).Univariate analysis was used to determine the prognostic value of infiltrating immune cell counts as well as other clinical and pathological parameters. For those statistically significant factors in univariate analysis, a multivariate analysis (Cox proportional hazard model) was performed to explore the independent prognostic factors.The influence of TGF-β1 expressions on immune cell couts was evaluated using student T-test.Results1. univariate analysis:In univariate analysis, significant prognostic factors for Overall survival(OS) are: TNM stage(T stage, N stage, clinical stage),sex, age, tumor size, total number of examinated lymph nodes, distance from the upper and lower resection margins to macroscopic tumor borders(upper and lower resection margin distance). Intratumoral and peritumoral CD3+,CD68+cell counts and Intratumoral CD8+ cell counts. Among them, TNM stage, age, tumor size have reverse correlation to overall survival while number of examinated lymph nodes, extent of resection margins, Intratumoral and peritumoral CD3+, CD68+cell counts and Intratumoral CD8+ cell counts have positive correlation to overall survival, Female patients have poor prognosis than male patients.2. Multivariate analysis: 11 significant prognostic factors were chosen for multivariate analysis,they were T stage, N stage, sex, age,with or without chemotherapy,numbers of examinated lymph nodes, upper and lower resection margin distance, intratumoral CD3+,CD68+,CD8+cell counts l。The results shows that T stage, N stage, sex, with or without chemotherapy,numbers of examinated lymph nodes, intratumoral CD3+,CD68+cell counts are independent prognostic factors for Overall survival.3. Impacts of TGF-β1 on local immune response: The means of intratumoral CD68+cell counts for low and high TGF-β1 groups were 12.2±7.07 and 9.7±6.83 respectively, and the difference was statistically significant. The means of intratumoral CD3+cell counts for low and high TGF-β1 groups were 32.6±27.47 and 24.2±21.52 respectively, and the difference was statistically significant. High level of TGF-β1 expression is correlative to poor treatment outcome, but the difference is not statistically significant(p=0.06)Conclusions1. The counts of TAM and tumor infiltrating T cell reflect the anti-caner potiental of immune system, and are independent prognostic factors.2. TGF-β1 can reduce the number of tumor infiltrating immune cell, especially macrophages and tumor infiltrating T lymphocyted, which may be one of the mechanisms by which tumor escapes from immune surveillance.3. The number of examinated lymph nodes is essentially needed for a correct N stage. Careful examination of the resection specimens for the lymph nodes is very important. Resection margin should include at least 6cm of normal esophagus and stomach to avoice tumor residence. Postoperative chemotherapy may improve the long-term survival and remains a better management for gastric cardia carcinoma.
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