Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.
Histopathology. 2018 Oct;73(4):645-652. doi: 10.1111/his.13689. Epub 2018 Aug 2.
Ewing sarcoma is a small round cell tumour that affects bone and soft tissues. Although the detection of the specific fusion gene is a robust method of its diagnosis, immunohistochemistry may serve as a practical surrogate. Recent tissue microarray studies suggested that PAX7 is a novel marker, because it was expressed consistently in Ewing sarcoma, in addition to rhabdomyosarcoma and synovial sarcoma. Here, we evaluated the utility of PAX7 immunohistochemistry in whole-tissue sections of an expanded array of round cell malignancies with adequate molecular characterisation.
We stained 30 molecularly confirmed Ewing sarcomas, one EWSR1-NFATC2 sarcoma and 141 non-Ewing round cell tumours by a monoclonal antibody against PAX7. Staining was considered positive if at least 5% of tumour cells were stained. PAX7 was expressed in 27 of 30 Ewing sarcomas (90%), mainly in a diffuse and strong manner. Although NKX2-2 showed similar sensitivity, PAX7 showed more extensive and strong reactivity. One EWSR1-NFATC2 sarcoma co-expressed PAX7 and NKX2-2. PAX7 was also expressed in 24 of 141 non-Ewing tumours, including alveolar rhabdomyosarcomas (seven of 10), poorly differentiated synovial sarcomas (seven of 10), BCOR-CCNB3 sarcomas (eight of 10), small-cell osteosarcoma (one of five) and desmoplastic small round cell tumour (one of 10), one-third of which showed diffuse strong reactivity.
Although we confirmed that PAX7 is a sensitive marker for Ewing sarcoma, anti-PAX7 antibody also stained several Ewing sarcoma mimics, whose spectrum was distinct from NKX2-2-positive non-Ewing entities. Further studies are required to determine how PAX7 could be integrated into practice to classify small round cell tumours efficiently.
尤文肉瘤是一种影响骨骼和软组织的小圆细胞肿瘤。虽然检测特定的融合基因是其诊断的一种可靠方法，但免疫组织化学可能是一种实用的替代方法。最近的组织微阵列研究表明，PAX7 是一种新的标记物，因为它除了横纹肌肉瘤和滑膜肉瘤外，还在尤文肉瘤中一致表达。在这里，我们评估了 PAX7 免疫组织化学在具有充分分子特征的扩展小圆细胞恶性肿瘤全组织切片中的应用。
我们使用针对 PAX7 的单克隆抗体对 30 例分子证实的尤文肉瘤、1 例 EWSR1-NFATC2 肉瘤和 141 例非尤文小圆细胞肿瘤进行染色。如果至少有 5%的肿瘤细胞染色，则认为染色为阳性。PAX7 在 30 例尤文肉瘤中的 27 例（90%）中表达，主要以弥漫性和强方式表达。虽然 NKX2-2 具有相似的敏感性，但 PAX7 显示出更广泛和更强的反应性。1 例 EWSR1-NFATC2 肉瘤同时表达 PAX7 和 NKX2-2。PAX7 还在 141 例非尤文肿瘤中的 24 例中表达，包括肺泡横纹肌肉瘤（10 例中的 7 例）、低分化滑膜肉瘤（10 例中的 7 例）、BCOR-CCNB3 肉瘤（10 例中的 8 例）、小细胞骨肉瘤（5 例中的 1 例）和促结缔组织增生性小圆细胞肿瘤（10 例中的 1 例），其中三分之一表现为弥漫性强反应性。
尽管我们证实 PAX7 是尤文肉瘤的一种敏感标志物，但抗 PAX7 抗体也染色了几种尤文肉瘤模拟物，其谱与 NKX2-2 阳性非尤文实体不同。需要进一步研究以确定如何将 PAX7 有效地整合到实践中，以对小圆细胞肿瘤进行分类。
