尤文肉瘤分子病理学研究进展

doi:10.16150/j.1671-2870.2023.06.012

摘要/Abstract

摘要：

尤文肉瘤是一种罕见的小圆细胞恶性肿瘤，软组织与骨肿瘤世界卫生组织（World Health Organizition，WHO）分类第五版（2020年）将其归类于未分化小圆细胞肉瘤。尤文肉瘤由形态单一的小圆形细胞构成，免疫组织化学检测提示细胞膜CD99阳性，伴有不同程度的神经外胚层分化，并具有特征性的FET家族-ETS家族融合基因。手术联合化疗的治疗方式已将尤文肉瘤患者的5年生存率提高到约70%，但如患者诊断时已出现肿瘤转移，其5年生存率仍不到30%。随着分子病理学的飞速发展，尤文肉瘤的分子机制（特征性FET-ETS家族融合突变及常见伴随突变）也成为了研究热点。在诊断方面，研究者对尤文肉瘤特征性基因重排的不断深入了解，如罕见的TAF15-ETV4融合基因尤文肉瘤病例的发现，提示全基因组测序用于诊断尤文肉瘤的重要性已不容忽视。在治疗方面，许多针对特征性FET家族-ETS家族融合基因的药物正在临床试验中。2022年，尤文肉瘤的第一个重复出现的可作为分子治疗靶点的伴随突变——FGFR1突变被发现，提示伴随突变可能是尤文肉瘤分子治疗的突破点之一。2023年最新研究指出ETV6可能成为未来尤文肉瘤治疗的新靶点之一。本文总结尤文肉瘤的分子病理研究进展，并探讨其在尤文肉瘤的临床诊断、治疗和预后中的价值。

关键词: 尤文肉瘤, 分子病理学, 分子治疗

Abstract:

Ewing sarcoma is a rare malignant small round cell mesenchymal neoplasm with a characteristic FET family-ETS family fusion gene, and is classified as undifferentiated small round cell sarcoma in the fifth revision of the WHO Classification of Tumors of Soft Tissue and Bone (2020）. Microscopically, Ewing sarcoma is composed of a monomorphic round cell population, accompanied by different degrees of neuroectodermal differentiation. Although surgery combined with chemotherapy has increased the 5-year survival rate of Ewing sarcoma to about 70%, the 5-year survival rate of patients with metastases at diagnosis is still less than 30%. With the rapid development of molecular pathology, the molecular mechanism of Ewing sarcoma has also become a focus of research. This article reviews the latest research progress on the unique pathological features, molecular mechanisms and genetic diagnostic criteria of Ewing sarcoma, in order to provide a new direction for the clinical diagnosis, treatment and prognosis of Ewing sarcoma.

Key words: Ewing sarcoma, Molecular pathology, Molecular therapy

中图分类号:

刘蘅安, 王朝夫. 尤文肉瘤分子病理学研究进展[J]. 诊断学理论与实践, 2023, 22(06): 587-592.

LIU Hengan, WANG Chaofu. Advances in molecular pathology of Ewing sarcoma[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(06): 587-592.

图/表 1

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融合基因	染色体易位	百分比
EWSR1-FLI1	t(11;22)(q24;q12)	85%
EWSR1-ERG	t(21;22)(q22;q12)	10%
其余FET-ETS基因家族融合基因	-	罕见