B7-H3和CD68＋肿瘤相关巨噬细胞与膀胱尿路上皮癌中的相关性及其对预后的意义  

The association and prognostic significance of B7-H3 with CD68 ＋ tumor-associated macrophages in urothelial cell carcinoma

作　　者：徐芝立[1] 王玲[1] 田建华[2] 梁长春[3] 满宏伟[1] 李鹏飞[1] 单亚楠[1] 单保恩[1] 

机构地区：[1]河北医科大学第四医院河北省肿瘤医院肿瘤研究所,石家庄市050011 [2]河北医科大学第四医院河北省肿瘤医院泌尿外科,石家庄市050011 [3]石家庄市第三医院泌尿外科

出　　处：《中华泌尿外科杂志》2016年第6期470-474,共5页Chinese Journal of Urology

摘　　要：目的 研究B7-H3、CD68＋肿瘤相关巨噬细胞（TAMs）的表达、浸润与膀胱尿路上皮癌临床病理参数的相关性,探讨其对患者预后的指导意义.方法 采用免疫组织化学法检测2008-2010年我院76例根治性膀胱切除术患者尿路上皮癌组织中B7-H3分子的表达以及肿瘤组织中CD68＋TAMs的浸润程度,并进行生存分析.男63例,女13例.年龄41～86岁,中位年龄65.5岁.结果 76例患者中,B7-H3阳性高表达54例（71.1％）,明显高于癌旁（23.3％）和正常膀胱组织（16.7％）的表达率（P＜0.05）.膀胱癌组织中,B7-H3高表达患者性别、年龄,病理分级、分期,复发,淋巴结转移等指标与B7-H3低表达患者相比,差异均无统计学意义（P＞0.05）;CD68＋ TAMs高浸润患者上述临床病理指标与低浸润患者相比,差异亦无统计学意义（P＞0.05）,但B7-H3高表达、CD68＋ TAMs高浸润患者的肿瘤远转移率分别高于B7-H3低表达和CD68＋ TAMs低浸润患者（40.7％ vs.13.6％：50.0％ vs.22.9％）,差异有统计学意义（P=0.023;P=0.015）.Spearman相关分析显示CD68＋TAMs浸润程度和B7-H3表达水平呈正相关（r=0.307,P=0.007）.B7-H3高表达患者中位总体生存时间（0S）、无进展生存时间（PFS）明显低于低表达患者（50个月vs.70个月,P=0.004;33个月vS.59个月,P=0.006）.CD68＋ TAMs高浸润患者的OS、PFS与低浸润患者相比,差异无统计学意义（P＞0.05）;但在CD68＋ TAMs低浸润组中,B7-H3高表达患者中位OS、PFS均低于B7-H3低表达患者（50个月vs.68个月,P=0.034;26个月vS.59个月,P=0.024）.结论 B7-H3分子可以单独或联合CD68＋ TAMs作为评估尿路上皮癌患者根治性膀胱切除术后肿瘤进展的有效指标.联合检测B7-H3分子和CD68＋ TAMs在膀胱癌患者预后判断及靶向治疗中具有潜在的临床应用价值.Objective To investigate the expression of B7-H3 and the infiltration by CD68 ＋ tumor-associated macrophages （TAMs） in urothelial cell carcinoma （UCC） of the bladder and evaluate its potential prognostic significance for bladder cancer.Methods Data from 76 consecutive UCC patients （63 males and 13 females）,median age 65.5 years（ranging from 41 to 86 years）,who underwent radical cystectomy,was collected.Immunohistochemistry for B7-H3 expression and CD68 ＋ TAMs infiltration was performed on tumor tissues to explore their association with clinicopathologic features and postoperative survival.Results B7-H3 was widely expressed in UCC,as 54 of 76 （71.1%） tumors showed high expression of positive staining,and significantly increased compared with adjacent,nontumor urothelium （P 〈 0.05）.The B7-H3 expression and infiltration of CD68＋ TAMs were independent of gender,age,tumor stage,grade,recurrence,lymphoid metastasis,yet both of them were markedly associated with distant metastasis of tumor （P =0.023;P=0.015）.In addition,CD68 ＋ TAMs infiltration and B7-H3 expression have significantly positive correlation （P =0.007）.Furthermore,Kaplan-Meier analysis showed that overall survival and progression-free survival of patients with high B7-H3 expression was significantly worse than those with low B7-H3 expression （50 months vs.70 months,P =0.004;33 months vs.59 months,P =0.006）,while CD68 ＋ TAMs infiltration was not independently associated with OS and PFS in the same cohort.But,in low CD68 ＋ TAMs infiltration subgroup,the median OS and PFS in patients with high B7-H3 expression were shorter than patients with low B7-H3 expression （50 months vs.68 months,P =0.034;26 months vs.59 months,P =0.024）.Conclusions This study is the first report of B7-H3 expression and CD68 ＋ TAMs infiltration in urothelial cell carcinoma of bladder in China.B7-H3 is highly expressed in UCC tissues,which could be used alone or in combination with CD68 ＋ TAMs for assessing tumor progression after

关 键 词：B7-H3基因 CD68基因 肿瘤相关巨噬细胞 尿路上皮癌 生存分析 

分 类 号：R737.14[医药卫生—肿瘤]