TFEB重排肾细胞癌8例临床病理及分子生物学特征  

Renal cell carcinoma associated with TFEB gene rearrangement:a clinicopathological and molecular study of 8 cases

作　　者：杨亚蓝 郑林茂 尹晓雪[1] 张梦鑫 卫昱燕 张孟尼 聂玲[1] 陈铌[1] 陈雪芹[1] 周桥[1] Yang Yalan;Zheng Linmao;Yin Xiaoxue;Zhang Mengxin;Wei Yuyan;Zhang Mengni;Nie Ling;Chen Ni;Chen Xueqin;Zhou Qiao(Department of Pathology,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院病理科,成都610041

出　　处：《中华病理学杂志》2023年第3期236-242,共7页Chinese Journal of Pathology

基　　金：国家自然科学基金(81872108,81872107);四川省科技厅重点研发项目(2020YFS0191,2021YFS0114)。

摘　　要：目的:探讨TFEB重排肾细胞癌(TFEBr-RCC)患者的临床病理特征、免疫表型、分子遗传学特征及预后。方法:收集四川大学华西医院2014—2022年确诊的8例TFEBr-RCC,总结其组织病理形态特征、免疫组织化学、荧光原位杂交和RNA测序结果,并复习相关文献。结果:男性6例,女性2例。患者年龄25~50岁,平均年龄34岁,中位年龄32岁。3例位于右肾,5例位于左肾。肿瘤最大径4.0~18.5 cm,平均8.5 cm。5例具有典型的“假菊形团”双相结构;其余3例形态不典型,2例类似上皮样血管平滑肌脂肪瘤,1例类似透明细胞肾细胞癌。TFEB和PAX8免疫组织化学均呈弥漫核表达(8/8),部分病例行HMB45、MART1和细胞程序性死亡配体1(PD-L1)免疫组织化学检查,结果示多数病例表达HMB45(5/6)、MART1(7/7),PD-L1(5/5)。TFEB分离探针荧光原位杂交检测,显示8例均存在TFEB基因易位。5例行RNA测序,结果4例为MALAT1-TFEB基因融合(包括2种新的MALAT1-TFEB融合方式),1例为1种新的ACTB-TFEB基因融合。本组病例随访5~96个月,平均随访时间47个月,截至2022年7月患者均无病生存,未见复发和转移。结论:TFEBr-RCC好发于青壮年,预后较好。形态学主要表现为特征性“假菊型团”双相结构,亦可表现为上皮样血管平滑肌脂肪瘤样或透明细胞肾细胞癌样形态。免疫组织化学呈TFEB核阳性,不同程度表达黑色素细胞分化标志物,且多表达PD-L1。MALAT1-TFEB基因融合为TFEBr-RCC最主要的融合形式,但融合位点不恒定。Objective To study the clinicopathological features,immunophenotype,molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement(TFEBr-RCC).Methods Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological,immunohistochemical,fluorescence in situ hybridization and RNA sequencing analyses,with review of literature.Results Six patients were male and two were female.The patient ages ranged from 25 to 50 years(mean:34 years,median:32 years).The tumors were present in the right kidney(3 cases)or the left kidney(5 cases).The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm,with an average of 8.5 cm.Histologically,majority of the cases(5/8)showed typical biphasic"pseudorosette"structure,while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma.Immunohistochemical study showed positivity of TFEB(8/8),PAX8(8/8),MART-1(7/7),and HMB45(5/6).Interestingly,PD-L1 was variably expressed in all five tested cases.Staining for TFE3 in all cases was negative.TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization.RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases(two of which showing novel MALAT1-TFEB fusion sites),and one case with a novel ACTB-TFEB gene fusion.Patient follow-ups ranged from 5 to 96 months(average 47 months).All patients were alive without recurrence or metastasis.Conclusions TFEBr-RCC tends to occur in young adults and has a good prognosis.Histologically,most of the cases show characteristic biphasic structure,and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology.Immunohistochemical reactivity to TFEB,melanocytic markers and PD-L1 is characteristic.MALAT1-TFEB gene fusion is the most common molecular change,with variable fusion sites.

关 键 词：癌 肾细胞 分子生物学 病理学 临床 预后 

分 类 号：R737.11[医药卫生—肿瘤]