延胡索酸水合酶缺陷型肾细胞癌中PD-L1表达及其临床病理免疫特征  

Expression of programmed cell death ligand 1 and clinicopathological and immunological characteristics in fumarate hydratase-deficient renal cell carcinoma

作　　者：陈施 班超然 张昕婷 陈余朋[1] 任彩虹[1] 陈虹[1] Chen Shi;Ban Chaoran;Zhang Xinting;Chen Yupeng;Ren Caihong;Chen Hong(Department of Pathology,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院病理科,福州350005

出　　处：《中华病理学杂志》2024年第2期155-161,共7页Chinese Journal of Pathology

基　　金：福建省自然科学基金(2023J01583);国家临床重点专科建设科研项目(2022YBL-ZD-04)。

摘　　要：目的探讨延胡索酸水合酶(FH)缺陷型肾细胞癌的细胞程序性死亡配体1(PD-L1)的表达情况、临床病理特征、免疫组织化学表达及分子特征,探寻免疫治疗在FH缺陷型肾细胞癌中的应用前景。方法对福建医科大学附属第一医院2020年1月至2022年10月收集的6例FH缺陷型肾细胞癌的PD-L1表达情况、临床资料、组织学形态、免疫表型、二代测序基因检测进行总结并随访预后。结果患者均为男性,年龄37~72岁,平均年龄45.7岁。4例高级别FH缺陷型肾细胞癌病例均可见2种或2种以上的结构混杂存在,以乳头状结构最常见,还可见到腺管状、腺泡状、筛状、巢团状、囊性变、实性结构混杂存在,癌细胞WHO/国际泌尿病理协会(ISUP)核分级为3~4级。2例低级别FH缺陷型肾细胞癌病例表现为巢团状、腺管状排列,嗜酸性、絮状胞质及小的胞质内空泡。6例2-琥珀酸半胱氨酸(2SC)均为强阳性,5例FH表达丢失、GATA3阳性,4例高级别病例肿瘤浸润的CD4、CD8阳性的T淋巴细胞平均值分别是180.3/mm^(2)、130.5/mm^(2),PD-L1联合阳性评分(CPS)分别是20、50、5、30,Ki-67阳性指数分别为20%、20%、10%、30%;2例低级别病例肿瘤浸润的CD4、CD8阳性的T淋巴细胞平均值分别是123.0/mm^(2)、100.5/mm^(2),PD-L1 CPS评分均为1,Ki-67阳性指数均为3%。高通量测序3例检测到FH基因体系突变,2例检测到FH基因胚系突变,1例未测出FH基因突变。结论FH缺陷型肾细胞癌以高级别形态常见,低级别形态少见。FH和2SC是诊断FH缺陷型肾细胞癌特征性的免疫组织化学标志物,GATA3阳性对诊断具有提示作用。高级别FH缺陷型肾细胞癌肿瘤浸润的CD4、CD8阳性的T淋巴细胞增加,PD-L1高表达,抗PD-L1免疫治疗将可作为患者的治疗选择。Objective To investigate the expression of programmed cell death ligand 1(PD-L1),clinicopathologic features,immunohistochemical expression and molecular characteristics in fumarate hydratase(FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients.Methods There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022.The clinical data,histological morphology,immunophenotype,PD-L1 expression and next-generation sequencing results were tabulated and analyzed.Results There were 6 patients,all male,age ranged from 37 to 72 years(mean 45.7 years).Four cases were high-grade(WHO/ISUP grade3-4)with 2 or more histologic patterns,including papillary(most common),glandular,tubular,vesicular,ethmoid,nest-like,cystic and solid structures.Two cases were low-grade which showed nest-like,glandular,or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles.Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases,negative expression of FH in 5 cases,and positive expression of GATA3 in 5 cases.In high-grade cases,the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm^(2) and 130.5/mm^(2),respectively.PD-L1 combined positive scores(CPS)were 20,50,5 and 30,respectively.The Ki-67 proliferative index were 20%,20%,10%and 30%,respectively.In low-grade cases,the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm^(2) and 100.5/mm^(2),respectively.The PD-L1 CPS score was 1,and the Ki-67 proliferation index was 3%.High-throughput sequencing showed FH gene somatic mutation in 3 cases,FH gene germline mutation in 2 cases,and FH gene mutation was not detected in one case.Conclusion FH-deficient renal cell carcinoma is more commonly high-grade than low grade.FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma,and GATA3 positivity i

关 键 词：延胡索酸水合酶 癌 肾细胞 GATA3转录因子 程序性死亡配体1 

分 类 号：R737.11[医药卫生—肿瘤]