【摘要】 目的 探讨高级别子宫内膜间质肉瘤（HG-ESS）分子异常的致癌机制。方法 回顾性分析21例HG-ESS患者的临床病理资料，使用YWHAE单融合易位探针对肿瘤组织样本进行荧光原位杂交（FISH）。对于肿瘤组织可及的5例样本进行RNA测序以验证融合状态，对其中检出YWHAE-NUTM2B融合的样本进行免疫组织化学（IHC）和免疫荧光（IF）检测以验证是否为功能性融合，并基于Kaplan-Meier法和log-rank检验对YWHAE融合阳性与阴性亚组进行生存分析。结果 21例HG-ESS患者平均确诊年龄（46.1±12.6）岁，均出现阴道异常流血症状。FISH检测结果为阴性11例，阳性7例，不典型3例。组织可及的5例样本RNA测序结果提示在1例FISH阳性和1例FISH不典型患者中检出YWHAE-NUTM2B融合，3例FISH阴性样本未检出融合。经IHC和IF检测确认2例RNA测序阳性患者中该融合基因产物（14-3-3ε）核表达。Kaplan-Meier生存曲线提示YWHAE融合阳性组生存略优于阴性组，但两组差异无统计学意义（P>0.05）。结论 FISH和RNA测序是辅助诊断HG-ESS的有效技术，对于YWHAE融合检测FISH结果为阴性或不典型的HG-ESS患者，应进行RNA测序进一步确认YWHAE融合或其他特异性结构变异。更多还原

【Abstract】 Objective To investigate the carcinogenic mechanisms of molecular abnormalities in high-grade endometrial stromal sarcoma(HG-ESS). Methods The clinicopathological data of 21 patients with HG-ESS were retrospectively analyzed. Fluorescence in situ hybridization(FISH) was performed on the tumor samples using YWHAE single fusion translocation probe. RNA sequencing was performed on 5 patients with accessible tumor tissues to verify the fusion status. Immunohistochemistry(IHC) and immunofluorescence(IF) were performed for patients with YWHAE-NUTM2B fusion to verify the fusion function. Based on Kaplan-Meier method and log-rank test, survival analysis was performed on patients with positive and negative YWHAE fusion. Results The average age at diagnosis of the 21 HG-ESS patients was(46.1 ± 12.6)years old, and HG-ESS patients all had abnormal vaginal bleeding symptom. FISH results of 21 HG-ESS patients were negative in 11 cases, positive in 7 cases, and atypical in 3 cases. The RNA sequencing results of 5 accessible tissue samples showed that YWHAE-NUTM2B typical fusion was detected in 1 FISH-positive and 1 FISH-atypical patient, and no fusion was detected in 3 FISH-negative samples. The nuclear expression of the fusion gene product(14-3-3ε) was confirmed by IHC and IF in two cases with YWHAE-NUTM2B fusion detected using RNA sequencing. Kaplan-Meier survival curve suggested that the YWHAE fusion positive group survived slightly better than the YWHAE fusion negative group, but the difference between these two groups was not statistically significant(P > 0.05). Conclusions FISH and RNA sequencing methods are effective techniques for differential diagnosis of HG-ESS. RNA sequencing should be performed in HG-ESS patients with negative and atypical YWHAE fusion FISH results to check the presence of YWHAE fusion or other specific structural variants.更多还原