Fellinger E J, Garin-Chesa P, Glasser D B, Huvos A G, Rettig W J
Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Am J Surg Pathol. 1992 Aug;16(8):746-55. doi: 10.1097/00000478-199208000-00002.
The HBA71 antigen is an M(r) 30,000/32,000 cell surface glycoprotein (p30/32MIC2), encoded by the pseudoautosomal MIC2 gene on chromosomes X and Y, that is expressed in Ewing's sarcomas. Immunohistochemical studies demonstrate a striking specificity for HBA71 among neoplasms of diverse histologic types. In the present study, 43 cases of Ewing's sarcoma of bone were tested for HBA71 expression and six additional immunohistochemical markers regularly used in the differential diagnosis of small round-cell tumors of childhood and adolescence (neuron-specific enolase, vimentin, leukocyte common antigen, cytokeratins, muscle-specific actin, desmin). The study design included (a) random selection of Ewing's sarcoma cases from the files of Memorial Hospital beginning in 1968, (b) blind review of the original histopathologic diagnoses of ES, (c) side-by-side immunohistochemical study of recut histologic specimens, and (d) statistical analysis of immunohistochemical findings in view of clinical outcome. Of the seven antigens studied, only HBA71, neuron-specific enolase and vimentin were expressed in a significant proportion of cases. Forty-one of the 43 cases were HBA71+ (95% sensitivity); of these, 21 were neuron-specific enolase+, 29 were vimentin+, and 15 were both neuron-specific enolase+ and vimentin+. One tumor lacked all antigens, and one was vimentin+ only. Comparison of tumor tissues in five patients obtained before and after cytostatic chemotherapy showed no change in HBA71 expression or in the other antigens tested. Product-limit survival analysis (median disease-free survival was 27.3 months for the study cohort) revealed no significance of neuron-specific enolase or vimentin marker status. These results raise doubts about the usefulness of neuron-specific enolase and vimentin immunohistochemistry to distinguish Ewing's sarcoma from other small round-cell tumors of childhood and adolescence or as prognostic indicators in Ewing's sarcoma. The positive identification of Ewing's sarcoma of bone now becomes a reality using HBA71 immunohistochemistry, either as a sole method or in combination with chromosomal breakpoint analysis. This may result in achieving uniform diagnostic criteria for evaluating the biologic, therapeutic, and prognostic aspects of Ewing's sarcoma and related neoplasms.
HBA71抗原是一种分子量为30000/32000的细胞表面糖蛋白（p30/32MIC2），由X和Y染色体上的假常染色体MIC2基因编码，在尤因肉瘤中表达。免疫组织化学研究表明，HBA71在多种组织学类型的肿瘤中具有显著的特异性。在本研究中，对43例骨尤因肉瘤进行了HBA71表达检测，并检测了另外六种常用于儿童和青少年小圆细胞肿瘤鉴别诊断的免疫组织化学标志物（神经元特异性烯醇化酶、波形蛋白、白细胞共同抗原、细胞角蛋白、肌肉特异性肌动蛋白、结蛋白）。研究设计包括：（a）从纪念医院1968年以来的档案中随机选择尤因肉瘤病例；（b）对尤因肉瘤的原始组织病理学诊断进行盲法复查；（c）对重新切片的组织标本进行并行免疫组织化学研究；（d）根据临床结果对免疫组织化学结果进行统计分析。在所研究的七种抗原中，只有HBA71、神经元特异性烯醇化酶和波形蛋白在相当比例的病例中表达。43例中有41例HBA71阳性（敏感性95%）；其中，21例神经元特异性烯醇化酶阳性，29例波形蛋白阳性，15例神经元特异性烯醇化酶和波形蛋白均阳性。1例肿瘤所有抗原均为阴性，1例仅波形蛋白阳性。对5例患者在细胞抑制化疗前后获取的肿瘤组织进行比较，结果显示HBA71表达及所检测的其他抗原均无变化。乘积限生存分析（研究队列的无病生存期中位数为27.3个月）显示，神经元特异性烯醇化酶或波形蛋白标志物状态无显著意义。这些结果使人怀疑神经元特异性烯醇化酶和波形蛋白免疫组织化学在鉴别尤因肉瘤与其他儿童和青少年小圆细胞肿瘤或作为尤因肉瘤预后指标方面的实用性。使用HBA71免疫组织化学，无论是作为单一方法还是与染色体断点分析相结合，现在都能实现对骨尤因肉瘤的阳性鉴定。这可能会为评估尤因肉瘤及相关肿瘤的生物学、治疗和预后方面制定统一的诊断标准。
