目的 探讨CD8+ T细胞在膀胱癌组织中的分布特征及其与临床病理指标和预后的关系.方法 采用免疫组化染色方法检测2003年1月至2009年12月确诊的302例膀胱癌标本中CD8+ T细胞在组织原位的分布特征.302例中,男262例、,女40例.平均年龄60岁.肿瘤最大径≤3 cm者235例,＞3 cm者67例.肿瘤单发214例,多发88例.肿瘤分期Ta～T1期212例,T2～T4期90例.淋巴结无转移286例,有转移16例.病理分级低分级175例,高分级127例.根据解剖结构和细胞组成,将膀胱癌组织分为癌巢区域(肿瘤细胞组成为主)和间质区域(间质细胞组成为主).根据CD8 T细胞密度的中位值(癌巢:3个/高倍镜视野;间质:37个/高倍镜视野),将膀胱癌患者分为低密度组和高密度组.应用x2检验评价CD8+ T细胞密度与患者临床病理指标的相关性.利用Kaplan-Meier法及Cox模型进行生存分析.结果 免疫组化染色检查结果显示,CD8 T细胞在癌巢区域分布的平均值为(14±2)个/高倍镜视野,间质区域为(50±3)个/高倍镜视野,差异有统计学意义(P＜0.05).癌巢区域的CD8T细胞密度与患者年龄(P =0.026)、肿瘤大小(P＜0.05)和肿瘤分期(P＜0.05)呈负相关;间质区域的CD8 T细胞密度与患者年龄(P=0.004)和病理分级(P＜0.05)呈正相关.Kaplan-Meier生存分析结果示,癌巢中CD8+ T细胞密度与患者的总体生存时间呈正相关(P＜0.05).然而,间质中CD8+ T细胞密度与患者的总体生存时间呈负相关(P＜0.05).多因素分析结果显示,癌巢(HR=0.427,P=0.003)和间质中CD8+ T细胞密度(HR=2.206,P=0.009)可作为膀胱癌患者预后的独立预测指标.结论 膀胱癌组织中CD8+ T细胞广泛分布在癌巢和间质,癌巢中和间质中的CD8+ T细胞密度与患者的总体生存时间分布分别呈正相关和呈负相关.%Objective The aim of this study was to investigate the distribution and clinical significance of CD8+ T cells in bladder cancer tissues in situ.Methods Immunohistochemistry were used to examine the distribution of CD8+ T cells in bladder cancer tissues,which were obtained from January 2003 to December 2009 from 302 patients.Among all the patients,262 were male while 40 were female;mean age is 60 years;tumor size ≤ 3 cm was in 235 and tumor size ＞ 3 cm was in 67;Unifocal tumor was in 214 and multifocal tumors were in 88.Amount of tumor stage Ta-T1 was 212 and T2-T4 was 90.Sixteen patients have lymph node metastasis.Histological low grade was diagnosed in 175 and histological high grade was diagnosed in 127.According to the differences between anatomic structure and cellular composition,bladder tumor tissues can be classified to two localization patterns:(1) intratumoral regions,defined as tumor cell nests;(2) stromal regions,defined as stromal areas that lack direct contact with tumor cells.Therefore,we divided 302 bladder cancer patients into two groups based on the median frequency of intratumoral CD8+ T cells (median,3/× 400 high resolution) and stromal CD8+ T cells (median,37/× 400 high resolution),respectively.x2 analysis was used to evaluated the correlation between CD8+ T cell density and clinicalpathological variables.Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS).Results CD8+ T cells were predominantly located in the intratumoral regions (mean,14 ± 2/× 400 high resolution) rather than in associated stromal regions (mean,50 ± 3/× 400 high resolution,P ＜ 0.05).The density of intratumoral CD8+ T cells was inversely associated with age (P =0.026),tumor size (P ＜ 0.05) and tumor stage (P ＜ 0.05),and could represent a favorable prognostic predictor of OS (HR =0.427,P =0.003).However,the density of stromal CD8+ T cells was positively associated with age (P =0.004) and histological grade (P ＜ 0.01),and could represent an adverse prognostic predictor of OS (HR =2.206,P =0.009).Conclusions Our findings suggest that intratumoral/ stromal CD8+ T cells could potentially serve as favorable/ adverse prognostic markers for bladder cancer patients,respectively.
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