肿瘤浸润淋巴细胞与EBV相关性胃癌侵袭及预后分析

Relationship of tumor-infiltrating lymphocytes with progress and prognosis in EBV-associated gastric cancers

目的探讨表达叉头框蛋白3(forkhead box P3,FOXP3)、CD8和CD4的浸润性淋巴细胞在EBV相关性胃癌进展及预后评估中的意义。方法采用免疫组化法检测61例EBV相关性胃癌及299例EBV阴性富于淋巴间质胃癌肿瘤浸润淋巴细胞中FOXP3、CD8和CD4的表达,计数阳性淋巴细胞,并分为高浸润组及低浸润组,分析其与临床病理特征及预后的相关性。结果EBV相关性胃癌组中FOXP3^+、CD8^+和CD4^+浸润性淋巴细胞数及CD8^+/CD4^+比值均大于EBV阴性胃癌组(P <0. 001)。EBV相关性胃癌FOXP3^+和CD8^+淋巴细胞高浸润组比低浸润组肿瘤浸润深度浅,脉管内癌栓形成率较低,5年生存率高(P <0. 05)。EBV阴性富于淋巴间质胃癌中FOXP3^+、CD8^+淋巴细胞浸润与预后无明显相关。结论 EBV相关性胃癌具有独特免疫微环境,FOXP3^+和CD8^+淋巴细胞浸润均与其肿瘤进展及预后相关。

Purpose To evaluate the progressive and prognostic implications of FOXP3+,CD8+and CD4+tumor-infiltrating lymphocytes in EBV-associated gastric cancers.Methods FOXP3,CD4 and CD8 immunohistochemical stains on tissue microarray were used in 61 cases of EBV-associated gastric cancer and 299 cases of EBV negative lymphocyte-rich gastric cancers surgically resected.Lymphocytes infiltration was observed and counted,and then the relationship between tumor-infiltrating lymphocytes and clinicopathological characteristics and prognosis were analyzed statistically.Results The number of FOXP3+,CD8+,CD4+T lymphocytes and the ratio of CD8+/CD4+in EBV-associated gastric cancer were significantly higher than EBV-negative lymphocyte-rich gastric cancer(P<0.001).In EBV-associated gastric cancer,higher density of FOXP3+and CD8+T lymphocytes infiltrating occurred more frequently in shallower invasion,less tumor thrombus within the vessel and better survival(P<0.05).FOXP3+and CD8+T lymphocytes infiltrates were not associated with prognosis in EBV-negative lymphocyte-rich gastric cancer.Conclusion EBV-associated gastric cancer has unique immune microenvironment,and infiltrating of FOXP3+and CD8+T lymphocytes is related to clinicopathological characteristics and prognosis in EBV-associated gastric cancer.