膀胱肉瘤样尿路上皮癌临床病理特征及端粒酶逆转录酶基因启动子突变分析

Clinicopathologic features and TERT promoter mutation of sarcomatoid urothelial carcinoma in urinary bladder

目的探讨膀胱肉瘤样尿路上皮癌的临床病理特征、免疫表型、端粒酶逆转录酶(telomerase reverse transcriptase,TERT)基因启动子突变情况。方法选取首都医科大学附属北京潞河医院2011年1月至2015年12月收治的11例膀胱肉瘤样尿路上皮癌患者,分析临床病理学特征,并进行免疫组化染色,检测TERT基因启动子突变。结果组织学显示上皮和间叶双向分化的特性,上皮成分均为高级别尿路上皮癌,可伴鳞状或腺样分化;间叶成分表现为多种形态,大部分呈梭形细胞弥漫性或流水样排列,还可表现黏液样结构或恶性纤维组织细胞瘤样或假血管肉瘤样结构。免疫组化染色显示上皮性区域AE1/AE3(+),EMA不同程度(+),Vimentin(-);肉瘤样区域Vimentin(+),AE1/AE3呈散在多点阳性;6例表达CK5/6,4例CK14,5例P63,5例GATA3,4例UroplakinⅡ,2例SMA,4例EGFR;HER-2、BRAF V600E、S-100、LCA、HMB45、CD34均为阴性;Ki-67阳性率为40%~70%。7例存在TERT基因启动子突变,突变类型均为C228T。11例均获得随访,术后随访2~30个月,平均生存期为12个月。结论膀胱肉瘤样尿路上皮癌是尿路上皮癌的罕见亚型,组织形态学表现各异,鉴别较困难,需要借助免疫组化以诊断,预后差,TERT基因有望成为治疗的新靶点。

Objective To investigate the clinicopathological features,immunopheotype and TERT promoter mutation of sarcomatoid urothelial carcinoma in urinary bladder.Method 11 cases were retrospectively collected,clinicopathological features and immunophenotype were reviewed combined with genetic mutation analysis of TERT.Result It was an unusual malignancy characterized by an intimate admixture of malignant epithelial elements and malignant soft tissue elements.The epithelial component had immunoreactivity for keratin AE1/AE3,EMA;the sarcomatoid component had immunoreactivity for Vimentin,AE1/AE3.The tumor cells were positive for CK5/6(6 cases),CK14(4 cases),P63(5 cases),GATA3(5 cases),UroplakinⅡ(4 cases),SMA(2 cases),EGFR(4 cases);the expression of HER-2,BRAF V600E,S-100,LCA,HMB45,CD34 were all negative.Gene mutation analysis showed that 7 cases had TERT promoter mutation.All patients were followed up for 2 to 30 months,with an average survival time of 12 months.Conclusion Scarcomatoid urothelial carcinoma in urinary bladdder is a rare tumor with highly malignant potential and distinct morphologic features.The prognosis is generally poor.TERT promoter mutation may be a new target gene for the treatment.