Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Genes Chromosomes Cancer. 2020 Sep;59(9):525-534. doi: 10.1002/gcc.22857. Epub 2020 May 28.
The genetic hallmark of classic Ewing sarcoma is a recurrent fusion between EWSR1 and FUS gene with a member of the ETS transcription factor family. In contrast, tumors with non-ETS gene partners have been designated until recently "Ewing-like sarcoma," as a provisional molecular entity, as their clinical and pathologic features were still evolving. However, this group was reclassified as "round cell sarcoma with EWSR1-non-ETS fusions" in the latest 2020 WHO classification. Moreover, round cell sarcomas with either CIC or BCOR gene abnormalities, initially classified under Ewing family of tumors, are now regarded as stand-alone pathologic entities based on their distinct features. In this study we investigated the clinical characteristics of 226 confirmed Ewing sarcoma patients (EWSR1-FLI1 [n = 176], EWSR1/FUS-ERG [n = 35], EWSR1/FUS-FEV [n = 12], and EWSR1-ETV1/4 [n = 3]) and 14 round cell sarcoma patients with EWSR1-non-ETS fusion (EWSR1/FUS-NFATC2 [n = 10], EWSR1-PATZ1 [n = 3], and EWSR1-VEZF1 [n = 1]). The impact on overall survival (OS) was assessed in 90 patients with available follow-up, treated between 2011 and 2018. Patients with fusions involving FEV and NFATC2 genes showed an older median age at diagnosis, compared to those with EWSR1-FLI1 (P = .005), while extraskeletal location was more common in tumors with noncanonical EWSR1-FLI1 fusions (P = .001). Axial and pelvic primary sites were more common in patients with EWSR1-FLI1 (72%), while tumors with NFATC2 fusions were more frequent in the limb (78%, P = .006). The 3-year OS in patients with EWSR1-FLI1 was 91%, compared to only 60% in patients with alternative fusions (P = .037); the latter group showing a higher rate of metastases at presentation. However, this OS difference was not significant in patients with localized tumor (P = .585). Our study demonstrates significant correlations between fusion subtype and age at presentation, primary tumor sites, and OS, in both conventional Ewing sarcoma and round cell sarcoma with EWSR1-non ETS fusions patients. Larger studies are needed to determine survival differences in localized tumors.
经典尤文肉瘤的遗传特征是 EWSR1 和 FUS 基因与 ETS 转录因子家族成员之间的反复融合。相比之下，直到最近，与非 ETS 基因伴侣的肿瘤仍被指定为“尤文样肉瘤”，作为一种暂定的分子实体，因为它们的临床和病理特征仍在不断发展。然而，在最新的 2020 年世界卫生组织分类中，该组被重新归类为“具有 EWSR1-非 ETS 融合的圆形细胞肉瘤”。此外，最初归类为尤文家族肿瘤的具有 CIC 或 BCOR 基因异常的圆形细胞肉瘤，现在根据其独特的特征被视为独立的病理实体。在这项研究中，我们研究了 226 例确诊尤文肉瘤患者（EWSR1-FLI1[n=176]、EWSR1/FUS-ERG[n=35]、EWSR1/FUS-FEV[n=12]和 EWSR1-ETV1/4[n=3]）和 14 例具有 EWSR1-非 ETS 融合的圆形细胞肉瘤患者（EWSR1/FUS-NFATC2[n=10]、EWSR1-PATZ1[n=3]和 EWSR1-VEZF1[n=1]）的临床特征。在可获得随访的 90 例患者中评估了总生存率（OS），这些患者于 2011 年至 2018 年接受治疗。与 EWSR1-FLI1 相比，涉及 FEV 和 NFATC2 基因融合的患者诊断时的中位年龄更大（P=0.005），而在具有非典型 EWSR1-FLI1 融合的肿瘤中，骨外部位更为常见（P=0.001）。轴性和骨盆原发性肿瘤在 EWSR1-FLI1 患者中更为常见（72%），而 NFATC2 融合的肿瘤在肢体中更为常见（78%，P=0.006）。EWSR1-FLI1 患者的 3 年 OS 为 91%，而其他融合患者的 3 年 OS 仅为 60%（P=0.037）；后者组在就诊时转移的发生率更高。然而，在局部肿瘤患者中，这一 OS 差异并不显著（P=0.585）。我们的研究表明，在常规尤文肉瘤和具有 EWSR1-非 ETS 融合的圆形细胞肉瘤患者中，融合亚型与发病年龄、肿瘤原发部位和 OS 之间存在显著相关性。需要更大的研究来确定局部肿瘤的生存差异。
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