摘要目的 探讨INI1在上皮样肉瘤(ES)中的免疫表型和分子遗传学改变及其在诊断中的作用.方法 收集20例ES患者的存档蜡块、临床病理资料,采用免疫组织化学法(EnVision法)检测相关免疫标志物,同时运用直接测序法及荧光原位杂交(FISH)方法检测ES中INI1基因的突变及缺失情况.结果 20例患者年龄范围16 ～ 75岁(平均40.2岁).其中经典型ES的平均年龄为37.9岁,而近端型ES的平均年龄为42.0岁.男女比例为1.2∶1.0.发病部位:经典型主要位于上下肢,而近端型常在会阴部及外生殖区.镜下经典型ES常由上皮样细胞和梭形细胞构成肉芽肿样结构常伴中心坏死,肿瘤细胞胞质红染,上皮样细胞常位于结节中心,逐渐过渡为周围梭形细胞,细胞间有丰富的胶原穿插其中.近端型ES呈多结节弥漫结构,细胞以上皮样大细胞为主,细胞异型性明显.少数病例以横纹肌样细胞为主与恶性横纹肌样瘤在形态学上无法区分.免疫组织化学结果显示:20例波形蛋白均弥漫阳性,CKpan、CK8、上皮细胞膜抗原(EMA)、CD34的阳性表达率分别为16/20、15/20、18/20、13/20.CK7仅1例阳性且为灶性.S-100蛋白的阳性率为5/20,且均为灶性及弱阳性.CD31、HMB45均为阴性.INI1在经典型ES和近端型ES中的失表达率分别为10/13和5/7.INI1基因的突变仅出现在1/6的ES中,为两个位点的错义突变,而纯合性缺失,杂合性缺失及单倍体出现于8/11的病例.结论 ES组织学上变异大,有多种形态学亚型,诊断上困难较大.INI1表达缺失在ES中频繁出现.结合病史,联合应用INI1、CKpan、CK8、EMA、CD34等指标,对ES诊断及鉴别诊断有帮助.ES中INI1失活的机制与INI1基因的缺失关系密切而不是突变.

abstractsObjective To study the immunophenotype and molecular genetics of epithelioid sarcoma (ES),INI1 expression and its role in differential diagnosis.Methods Twenty cases of ES were retrieved from the archival files and selected for immunohistochemical study,DNA sequencing and fluorescence in-situ hybridization.The clinical and pathologic features were also reviewed.Results The age of patients ranged from 16 to 75 years (mean =40.2 years).The median age of patients in classic ES and proximal-type was 37.9 years and 42.0 years,respectively.The male-to-female ratio was 1.2∶ 1.0.Classic ES mostly occurred in the extremities while proximal-type ES often affected the perineum and external genitalia and trunk.Histologically,granuloma-like structures,consisting of aggregates of epithelioid and spindly tumor cells with central necrosis,were observed in classic ES.The epithelioid tumor cells contained abundant eosinophilic cytoplasm,merged with spindly cells at the periphery and admixed with collagen fibers.In proximal-type ES,the tumor cells showed prominent epithelioid and/or rhabdoid features,had marked cytologic atypia and grew in multinodular or diffuse patterns.In 2 cases of proximal-type ES studied,the "rhabdoid" tumor cells demonstrated a diffuse sheet-like growth pattern,mimicking malignant rhabdoid tumor,Inmunohistochemical study showed that vimentin was positive in all cases.Pan-cytokeratin,CK8,CK7,epithelial membrane antigen and CD34 were expressed in 16,15,1,18 and 13 cases,respectively.The staining for S-100 protein was focal and weak in 5 cases.None of the cases studied expressed CD31 and HMB45.Loss of INI1 was demonstrated in 10 of the 13 classic ES cases and 5 of the 7 proximal-type ES cases.The mutation of INI1 gene was detected in 1 of the 6 cases.Deletion of INI1 gene including heterozygous deletion,homozygous deletion and haploid was observed in 8 of the 11 cases.Conclusions Owing to the histologic heterogeneity,pitfalls in diagnosis of ES sometimes are encountered.INI1 is lost in most cases of ES.Immunohistochemical study,including staining for INI1,provides useful clues in pathologic diagnosis.Instead of INI1 mutation,inactivation of INI1 gene related deletion is not uncommon.