BRAF V600E突变在成人肾母细胞瘤中的临床病理学分析

Clinicopathological features of adult Wilms tumor with BRAF V600E mutation

目的探讨成人肾母细胞瘤中BRAF V600E突变与后肾腺瘤样形态学之间的联系及其临床病理学特征。方法回顾性分析复旦大学附属肿瘤医院2012—2021年诊断的19例成人肾母细胞瘤临床资料,2位病理学医师进行HE形态学复核,选取代表性组织进行免疫组织化学(IHC)分析及BRAF V600E突变基因测序。结果组1为部分区域显示后肾腺瘤形态特征的成人肾母细胞瘤,共6例;组1中5例病理形态为上皮为主型且阳性表达WT-1与CD56,均表达CD57,6例患者Ki-67阳性指数不同区域差异巨大(1%~60%),5例免疫组织化学呈现不同程度的BRAF阳性表达,DNA测序结果显示5例免疫组织化学阳性病例均提示BRAF V600E第15号外显子呈突变型;组1病例随访23~71个月,均存活。组2为经典型肾母细胞瘤(无后肾腺瘤样区域),共13例;可供检测的7例组织中均无BRAF V600E突变。结论BRAF V600E突变高发于具有区域后肾腺瘤样形态的成人肾母细胞瘤,该类肿瘤可能代表了后肾腺瘤与肾母细胞瘤之间的过渡状态,预后较好且具有靶向治疗价值。

Objective To identify BRAF V600E mutations in adult Wilms tumor(WT)with overlapping histologic features of metanephric adenoma(MA)and to investigate the clinicopathological features of adult WT.Methods The clinical features of adult WT diagnosed at the Fudan University Shanghai Cancer Center,Shanghai,China from 2012 to 2021 were reviewed.HE-stained slides of all cases were reviewed by 2 expert pathologists.Representative tissues were selected for BRAF V600E immunohistochemical(IHC)staining and gene sequencing.Results In adult WT with MA-like areas(cohortⅠ,n=6),5 of the 6 cases were composed of epithelial-predominant and were positive for WT-1 and CD56,respectively,and all were positive for CD57.All 6 cases revealed highly variable Ki-67 indices,ranging from 1%in some areas to 60%in others.5 of the 6 cases harbored a BRAF V600E mutation.All cases in cohort I were followed up for 23 to 71 months,and all survived.In classical adult WT without MA-like areas cohort(cohortⅡ,n=13),all 7 cases with available material were negative for BRAF by IHC and none of them had any BRAF mutation.Conclusions BRAF V600E mutations are frequently present in adult WT with overlapping morphologically features of MA,but not in those without.More importantly,adult WTs with overlapping histologic features of MA may be an intermediate entity between typical MA and WT that may have a favorable prognosis and possible therapeutic targets.