联合调节性T与记忆T淋巴细胞检测在无门静脉侵犯肝细胞癌预后分析中的价值

The Value of Regular T and Memory T Lymphocytes in Analyzing Prognosis of HCC without Portal Vein Invasion

目的:探讨无门静脉侵犯(包括肉眼和镜下)肝细胞癌(hepatocellular carcinoma,HCC)局部微环境中免疫活性细胞与预后的关系。方法:选取167份在复旦大学附属中山医院肝外科患者接受首次根治性切除,并经组织病理学证实为无肉眼和镜下门静脉侵犯的HCC石蜡标本,利用高通量组织微阵列及免疫组织化学染色方法检测肝癌局部微环境中Foxp3+调节性T细胞(FOXP3+Treg)、CD45RO+记忆T淋巴细胞(CD45RO+TILs)分布及数目,并分析这2类细胞与患者预后的关系。结果:(1)CD45RO+TILs细胞数分布表现为癌周远大于癌内,而FOXP3+Treg则相反。(2)癌内CD45RO+TILs数目与无瘤生存率(DFS)和总生存率(OS)均呈显著正相关(P<0.001,P=0.003);而FOXP3+Treg无论在癌内还是癌周都与总生存率显著负相关(P=0.034,P=0.033),与无瘤生存率却无显著相关。(3)将癌内微环境中FOXP3+Treg联合CD45RO+TILs分组分析,发现FOXP3+Treg少,同时CD45RO+TILs多者DFS和OS均较好(I组);而反之,FOXP3+Treg多,同时CD45RO+TILs少者DFS和OS均较差(IV组)。结论:FOXP3+Treg与CD45RO+TILs的比例关系是无门静脉侵犯的HCC患者转移、复发和总生存的独立预测指标,其预测能力优于其他临床病理特征,包括TNM分期。

Objective：To investigate the relationship of immune activated cells with prognosis of HCC patients absence of portal vein invasion.Methods： In this study we enrolled a cohort of 167 HCC patients who underwent curative resection in Zhongshan Hospital,Fudan University from Jan 2002 to Dec 2006.They were confirmed after pathology as absence of tumor micro and macro vascular invasion.We researched Foxp3＋regular T cells and CD45RO＋memery T cells in tumor microenvironment and their relationships with prognosis of early HCC using immunohistochemisty and tissue microarrays.Results： ① the intratumoral number of FOXP3＋Treg were greater than the peritumoral number,CD45RO＋TILs in peritumoral tissue were by far more than intratumoral.② CD45RO＋TILs in intratumoral were positive associated to DFS and OS（P0.001,P=0.003）;Foxp3＋Treg in either intratumoral or peritumoral were strongly inverse related to OS（P=0.034,P=0.033）.③ in intratumoral,both DFS and OS in the group（group I） with high Foxp3＋Tregs and low CD45RO＋TILs were worse than the group（group IV） with low Foxp3＋Tregs and high CD45RO＋TILs.Conclusions： It is confirmed that,the proportional relationship between Foxp3＋Treg and CD45RO＋TILs is an independent predictor for DFS and OS in early HCC patients,the ability of prediction is priorer than others clinical characters including TNM.