Hojný Jan, Dvořák Jiří, Vránková Romana, Bártů Michaela Kendall, Hájková Nikola, Krkavcová Eva, Flídrová Miroslava, Stružinská Ivana, Němejcová Kristýna, Bouda Jiří, Michalová Květoslava, Cibula David, Poncová Renata, Rys Janusz, Ksiazek Mariusz, Jędryka Marcin, Poprawski Tymoteusz, Berjón Alberto, Zapardiel Ignacio, Laco Jan, Ndukwe Munachiso, Klát Jaroslav, Židlík Vladimír, Krasznai Zoard Tibor, Poka Robert, Zikán Michal, Špůrková Zuzana, Bizoń Magdalena, Sawicki Włodzimierz, Volodko Nataliya, Yezhova Iryna, Ciccarone Francesca, Zinicola Giulia, Bobiński Marcin, Ostrowska-Leśko Marta, Franin Ivan, Kekić Mirela, Piatnytska Tetiana, Varchak Ihor, Pilka Radovan, Marek Radim, Hausnerová Jitka, Koblížková Michaela, Havelka Pavel, Kalist Vladimír, Stukan Maciej, Grabowska Karolina, Kolníková Georgína, Krkoška Milan, Halaška Michael, Drozenová Jana, Stolnicu Simona, Capilna Mihai, Sharashenidze Archil, Gudadze Miranda, Matěj Radoslav, Dundr Pavel
Department of Obstetrics and Gynecology, Charles University Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Department of Obstetrics and Gynecology, Charles University Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Lab Invest. 2025 May 24;105(9):104198. doi: 10.1016/j.labinv.2025.104198.
Low-grade endometrial stromal sarcomas (LG-ESS), high-grade ESS (HG-ESS), undifferentiated uterine sarcomas (UUS), and uterine tumors resembling ovarian sex cord tumors are distinct non-smooth muscle cell neoplasms with varying clinical outcomes, often exhibiting overlapping characteristics. Diagnosis can be supported by identifying characteristic recurrent translocations, which may be absent in some cases, complicating the distinction of equivocal cases. Additionally, cases with overlapping features of low-grade and high-grade characteristics are recognized. To address these challenges, we analyzed RNA-seq profiles of 262 cases. Our results revealed that LG-ESS, with and without recurrent fusions, clustered into 2 partially overlapping expression profiles associated with distinct overall and relapse-free survival outcomes, with the cluster containing a majority of fusion-negative tumors demonstrating better prognoses. uterine tumors resembling ovarian sex cord tumors expression profiles closely resembled those of both LG-ESS subgroups, with NCOA3 fusion-positive cases clustering in groups with better survival outcomes. Furthermore, a distinct cluster for HG-ESS with BCOR and YWHAE fusions was identified, differentiating these tumors from HG-ESS without fusions. ONECUT3 emerged as a potential specific marker for this HG-ESS-fusion entity. A significant expression overlap was observed between monomorphic HG-ESS without fusions and pleomorphic UUS. These samples separated further into 2 mixed clusters distinguished by differences in immune activity, which significantly influenced overall survival and relapse-free survival outcomes. Unsupervised clustering of UUS revealed subgroups resembling either HG-ESS or muscle-cell-differentiated tumors, suggesting that UUS may include poorly differentiated distinct entities, such as leiomyosarcoma, and that the distinction from HG-ESS may, in some cases, be arbitrary. Our transcriptome analysis highlights several entities with distinct survival characteristics, providing a foundation for further characterization of these rare, often difficult-to-classify, tumors.
低级别子宫内膜间质肉瘤（LG-ESS）、高级别ESS（HG-ESS）、未分化子宫肉瘤（UUS）以及子宫肿瘤样卵巢性索肿瘤是不同的非平滑肌细胞肿瘤，临床结局各异，且常表现出重叠特征。可通过识别特征性的复发性易位来辅助诊断，但某些情况下可能不存在这种易位，这使得鉴别模棱两可的病例变得复杂。此外，还存在具有低级别和高级别特征重叠的病例。为应对这些挑战，我们分析了262例病例的RNA测序图谱。我们的结果显示，无论有无复发性融合的LG-ESS，都聚集成2个部分重叠的表达图谱，与不同的总生存期和无复发生存期结局相关，其中包含大多数融合阴性肿瘤的簇显示出更好的预后。子宫肿瘤样卵巢性索肿瘤的表达图谱与LG-ESS的两个亚组密切相似，NCOA3融合阳性病例聚集在生存结局较好的组中。此外，还识别出了具有BCOR和YWHAE融合的HG-ESS的一个独特簇，将这些肿瘤与无融合的HG-ESS区分开来。ONECUT3成为这种HG-ESS融合实体的一个潜在特异性标志物。在无融合的单形性HG-ESS和多形性UUS之间观察到显著的表达重叠。这些样本进一步分为2个混合簇，其区别在于免疫活性的差异，这显著影响了总生存期和无复发生存期结局。UUS的无监督聚类揭示了类似于HG-ESS或肌肉细胞分化肿瘤的亚组，这表明UUS可能包括分化差的不同实体，如平滑肌肉瘤，并且在某些情况下与HG-ESS的区分可能是随意的。我们的转录组分析突出了几个具有不同生存特征的实体，为进一步表征这些罕见且通常难以分类的肿瘤奠定了基础。
