BCOR Expression in Endometrial Stromal Sarcoma: A Single-Center Study

Hira  Nasir; Aribah  Atiq; Azra  Bashir; Akhtar Sohail  Chughtai; Omar  Chughtai; Faria Waqar  Khan

doi:10.54112/bcsrj.v6i6.1953

Authors

Hira Nasir Department of Histopathology, Chughtai Institute of Pathology, Lahore, Pakistan
Aribah Atiq Department of Histopathology, Chughtai Institute of Pathology, Lahore, Pakistan
Azra Bashir Department of Histopathology, Chughtai Institute of Pathology, Lahore, Pakistan
Akhtar Sohail Chughtai Department of Histopathology, Chughtai Institute of Pathology, Lahore, Pakistan
Omar Chughtai Department of Histopathology, Chughtai Institute of Pathology, Lahore, Pakistan
Faria Waqar Khan Department of Histopathology, Chughtai Institute of Pathology, Lahore, Pakistan

DOI:

https://doi.org/10.54112/bcsrj.v6i6.1953

Keywords:

Endometrial stromal sarcoma, BCOR, Immunohistochemistry, High-grade endometrial stromal sarcoma

Abstract

Endometrial stromal sarcoma (ESS) is a rare uterine neoplasm of mesenchymal origin that requires careful subcategorization due to its distinct prognostic implications. Recent studies have identified BCOR (BCL6 corepressor) as a reliable immunohistochemical marker with potential diagnostic value in high-grade ESS, aiding differentiation from other uterine sarcomas. Objective: To evaluate the diagnostic utility of BCOR expression in endometrial stromal sarcomas and to highlight its role in distinguishing high-grade ESS as a unique pathological entity for targeted treatment strategies. Methods: This prospective single-center study included 30 histologically confirmed cases of endometrial stromal neoplasms. Cases with insufficient tissue for immunohistochemistry or missing paraffin blocks were excluded. Formalin-fixed, paraffin-embedded tissue samples were subjected to BCOR immunohistochemical staining, and nuclear expression in tumor cells was assessed. Statistical analysis was performed to determine the association between BCOR expression and histological subtype. Results: Nuclear BCOR expression was detected in 3 (10.0%) of the 30 endometrial stromal neoplasms. All positive cases corresponded exclusively to high-grade ESS. Among nine cases of high-grade ESS, 3 (33.3%) exhibited BCOR expression, demonstrating a significant association with this subtype (p = 0.005). No BCOR expression was observed in endometrial stromal nodules, low-grade ESS, or undifferentiated uterine sarcomas. Conclusion: BCOR expression is a specific marker for high-grade ESS, facilitating its distinction from low-grade ESS, stromal nodules, undifferentiated uterine sarcomas, and other uterine pathologies. Incorporating BCOR immunostaining in diagnostic protocols may enhance diagnostic precision and guide individualized therapeutic approaches.

Downloads

Download data is not yet available.

References

Roy M, Musa F, Taylor SE, Huang M. Uterine Sarcomas: How to Navigate an Ever-Growing List of Subtypes. Am Soc Clin Oncol Educ Book. 2022;42:1-10. https://doi.org/10.1200/edbk_350955

Hoang L, Chiang S, Lee CH. Endometrial Stromal Sarcomas and Related Neoplasms: New Developments and Diagnostic Considerations. Pathology. 2018;50(2):162-177. https://doi.org/10.1016/j.pathol.2017.11.086

Alodaini AA. Uterine Mesenchymal Tumors: Updates on Pathology, Molecular Landscape, and Therapeutics. Medicina (Kaunas). 2024;60(7):1085. Published 2024 Jul 2. https://doi.org/10.3390/medicina60071085

Norris HJ, Taylor HB. Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors. Cancer. 1966;19(6):755-766. https://doi.org/10.1002/1097-0142(196606)19:6%3C755::aid-cncr2820190604%3E3.0.co;2-u

Wagh V, Menon S, Maheshwari A, Gupta S, Deodhar KK, Rekhi B. High-grade endometrial stromal sarcoma displaying immunohistochemical expression of BCOR-A report of two cases of a novel tumor entity. Indian J Pathol Microbiol. 2023;66(4):829-833. https://doi.org/10.4103/ijpm.ijpm_1021_22

Niu S, Zheng W. Endometrial stromal tumors: Diagnostic updates and challenges. Semin Diagn Pathol. 2022;39(3):201-212. https://doi.org/10.1053/j.semdp.2022.01.004

Verma A, Tomar R, Chaturvedi A, Dhankar N, Mallya V, Khurana N. Endometrial stromal tumors: A clinico-histomorphological spectrum of endometrial stromal tumors with review of literature. J Cancer Res Ther. 2024;20(1):150-155. https://doi.org/10.4103/jcrt.jcrt_741_22

Devins KM, Attygalle AD, Croce S, Vroobel K, Oliva E, McCluggage WG. Uterine Endometrial Stromal Tumors With Pure Low-Grade Morphology Harboring YWHAE::NUTM2 Fusions: Report of a Case Series Emphasizing Potential for High-Grade Transformation and Aggressive Behavior. Am J Surg Pathol. 2023;47(6):717-724. https://doi.org/10.1097/pas.0000000000002041

Pantelić M, Gvozdenovic L, Panjković M, et al. Manifestation of an undifferentiated uterine sarcoma in a 51-year-old patient and its prognosis: A case report. Medicine (Baltimore). 2022;101(52):e32552. doi:10.1097/MD.0000000000032552 https://doi.org/10.1097/md.0000000000032552

Hoang LN, Aneja A, Conlon N, et al. Novel High-grade Endometrial Stromal Sarcoma: A Morphologic Mimicker of Myxoid Leiomyosarcoma. Am J Surg Pathol. 2017;41(1):12-24. https://doi.org/10.1097/pas.0000000000000721

Lu B, Chen J, Shao Y, Shi H. Two cases of ZC3H7B-BCOR high-grade endometrial stromal sarcoma with an extension on its morphological features. Pathology. 2020;52(6):708-712. https://doi.org/10.1016/j.pathol.2020.05.007

Ricotta G, Russo SA, Fagotti A, et al. Endometrial Stromal Sarcoma: An Update. Cancers (Basel). 2025;17(11):1893. Published 2025 Jun 5. doi:10.3390/cancers17111893

https://doi.org/10.3390/cancers17111893

Alkanat NE, Uner A, Usubutun A. High-grade Endometrial Stromal Sarcoma: Morphologic and Clinical Features, the Role of Immunohistochemistry and Fluorescence in Situ Hybridization in Diagnosis. Int J Surg Pathol. 2023;31(5):521-531. https://doi.org/10.1177/10668969221098087

Chiang S, Lee CH, Stewart CJR, et al. BCOR is a robust diagnostic immunohistochemical marker of genetically diverse high-grade endometrial stromal sarcoma, including tumors exhibiting variant morphology. Mod Pathol. 2017;30(9):1251-1261. https://doi.org/10.1038/modpathol.2017.42

Capozzi VA, Monfardini L, Ceni V, et al. Endometrial stromal sarcoma: A review of rare mesenchymal uterine neoplasm. J Obstet Gynaecol Res. 2020;46(11):2221-2236. https://doi.org/10.1111/jog.14436

Astolfi A, Fiore M, Melchionda F, Indio V, Bertuccio SN, Pession A. BCOR involvement in cancer. Epigenomics. 2019;11(7):835-855. https://doi.org/10.2217/epi-2018-0195

Kao YC, Owosho AA, Sung YS, et al. BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas. Am J Surg Pathol. 2018;42(5):604-615. https://doi.org/10.1097/pas.0000000000000965

Aldera AP, Govender D. Gene of the month: BCOR. J Clin Pathol. 2020;73(6):314-317. https://doi.org/10.1136/jclinpath-2020-206513

Subbaraya S, Murthy SS, Devi GS. Immunohistochemical and Molecular Characterization of Endometrial Stromal Sarcomas. Clin Pathol. 2020;13:2632010X20916736. Published 2020 May 11. https://doi.org/10.1177/2632010x20916736

Leath CA 3rd, Huh WK, Hyde J Jr, et al. A multi-institutional review of outcomes of endometrial stromal sarcoma. Gynecol Oncol. 2007;105(3):630-634. https://doi.org/10.1016/j.ygyno.2007.01.031

Kao YC, Sung YS, Zhang L, et al. BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities. Am J Surg Pathol. 2016;40(12):1670-1678. https://doi.org/10.1097/pas.0000000000000697

Alabiad, M.A., Harb, O.A., Abdelfattah, M.T. et al. The values of Transgelin, Stathmin, BCOR, and Cyclin-D1 expression in differentiation between Uterine Leiomyosarcoma (ULMS) and Endometrial Stromal Sarcoma (ESS); diagnostic and prognostic implications. Surg Exp Pathol 3, 13 (2020). https://doi.org/10.1186/s42047-020-00065-0

Zou Y, Turashvili G, Soslow RA, et al. High-grade transformation of low-grade endometrial stromal sarcomas lacking YWHAE and BCOR genetic abnormalities. Mod Pathol. 2020;33(9):1861-1870. https://doi.org/10.1038/s41379-020-0535-y

Lewis N, Soslow RA, Delair DF, et al. ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity. Mod Pathol. 2018;31(4):674-684. https://doi.org/10.1038/modpathol.2017.162

Abouelkhair MB, Shakweer MM, Faisal MM, Nasreldin MH, Farid LM. Diagnostic Value of Combined BCOR, Cyclin D1, and CD10 in Differentiating Endometrial Stromal Sarcoma From Other Uterine Spindle Cell Lesions. Appl Immunohistochem Mol Morphol. 2024;32(7):326-335. https://doi.org/10.1097/pai.0000000000001213

Rahimi S, Akaev I, Marani C, Chopra M, Yeoh CC. Immunohistochemical Expression of Different Subtypes of Cytokeratins by Endometrial Stromal Sarcoma. Appl Immunohistochem Mol Morphol. 2019;27(6):466-470. https://doi.org/10.1097/pai.0000000000000642

Akaev I, Yeoh CC, Rahimi S. Update on Endometrial Stromal Tumours of the Uterus. Diagnostics. 2021; 11(3):429. https://doi.org/10.3390/diagnostics11030429

Kang N, Zhang Y, Guo S, et al. Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma. Cancer Res Treat. 2023;55(3):978-991. https://doi.org/10.4143/crt.2022.1647