Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of Endometrial Stromal Sarcomas, Uterine Tumors Resembling Ovarian Sex Cord Tumors, and Undifferentiated Uterine Sarcomas With Prognostic Insights

• Autoři: HOJNY Jan; DVORAK Jiri; VRANKOVA Romana; KENDALL BARTU Michaela; HAJKOVA Nikola; KRKAVCOVA Eva; FLIDROVA Miroslava; STRUZINSKA Ivana; NEMEJCOVA Kristyna; BOUDA Jiri; MICHALOVA Kvetoslava; CIBULA David; PONCOVA Renata; RYS Janusz; KSIAZEK Mariusz; JEDRYKA Marcin; POPRAWSKI Tymoteusz; BERJON Alberto; ZAPARDIEL Ignacio; LACO Jan; NDUKWE Munachiso; KLAT Jaroslav; ZIDLIK Vladimir; KRASZNAI Zoard Tibor; POKA Robert; ZIKAN Michal; SPURKOVA Zuzana; BIZON Magdalena; SAWICKI Wlodzimierz; VOLODKO Nataliya; YEZHOVA Iryna; CICCARONE Francesca; ZINICOLA Giulia; BOBINSKI Marcin; OSTROWSKA-LESKO Marta; FRANIN Ivan; KEKIC Mirela; PIATNYTSKA Tetiana; VARCHAK Ihor; PILKA Radovan; MAREK Radim; HAUSNEROVÁ Jitka; KOBLÍŽKOVÁ Michaela; HAVELKA Pavel; KALIST Vladimir; STUKAN Maciej; GRABOWSKA Karolina; KOLNIKOVA Georgina; KRKOSKA Milan; HALASKA Michael; DROZENOVA Jana; STOLNICU Simona; CAPILNA Mihai; SHARASHENIDZE Archil; GUDADZE Miranda; MATEJ Radoslav; DUNDR Pavel
• Rok publikování: 2025
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Laboratory Investigation
• Fakulta / Pracoviště MU: Lékařská fakulta
• www: https://www.sciencedirect.com/science/article/abs/pii/S0023683725001084?via%3Dihub
• Doi: https://doi.org/10.1016/j.labinv.2025.104198
• Klíčová slova: high-grade endometrial stromal sarcomas; low-grade endometrial stromal sarcomas; ONECUT3; RNA-seq; undifferentiated uterine sarcomas; uterine tumor resembling ovarian sex cord tumors
• Popis: 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-celledifferentiated 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. (c) 2025 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.