BCOR is a POZ/zinc finger transcriptional repressor, with its gene located in the Xp11.4 region, playing an important role in normal early embryonic development. Its genetic alterations in sarcomas include two major groups (as shown in Figure 1): one group is BCOR-rearranged sarcomas, with BCOR-CCNB3 sarcoma being the most common, and reports of BCOR-MAML3 and BCOR-ZC3H7B fusions also exist; the other group is BCOR internal tandem duplication (BCOR-ITD) alterations, including infantile undifferentiated round cell sarcoma (IURCS) and primitive myxoid mesenchymal tumor of infancy (PMMTI). In addition, BCOR positivity can also be seen in tumors such as clear cell sarcoma of the kidney and YWHAE‑NUTM2B fusion round cell sarcoma.
Figure 1. Schematic diagram of different BCOR genetic alterations
BCOR-rearranged sarcoma is associated with BCOR gene fusions, with BCOR-CCNB3 fusion cases accounting for about 60%. Patients are mostly children and adolescents, predominantly male, often involving the pelvis, lower limbs, and paravertebral regions, with visceral locations being relatively rare. Its 5-year survival rate is 72-80%, and the 10-year survival rate is 56%. Therefore, the identification of this tumor is helpful for clinical treatment.
Microscopically, this type of tumor is composed of varying proportions of round, oval, and spindle cells, and can also be dominated by either round cells or spindle cells, arranged in sheets, whorls, or bundles, and can be composed of a mixture of high and low cellular density areas. The tumor cell nuclei are relatively uniform in size, with fine chromatin and inconspicuous nucleoli. The stroma shows abundant dendritic capillaries, and there may be varying amounts of myxoid change or collagenous tissue. Necrosis is common and can be focal or geographic; mitotic figures can be seen (1-25/10 HPF). In recurrent and metastatic cases, tumor cell density increases, and cellular pleomorphism is obvious.
The study by Yu-Chien Kao et al. included 8 cases of BCOR-CCNB3 fusion sarcoma, 1 case of BCOR-MAML3 fusion sarcoma, and 133 cases of sarcomas without BCOR genetic alterations. IHC results showed that all BCOR-rearranged sarcomas exhibited diffuse strong nuclear positivity for BCOR expression. BCOR is not expressed in most other sarcoma types: only 2 out of 29 tested rhabdomyosarcomas (1 alveolar, 1 embryonal) and 1 out of 92 myxofibrosarcomas showed moderate BCOR staining. No BCOR staining was found in any chondrosarcoma, low-grade fibromyxoid sarcoma, or angiosarcoma tissue microarrays. This indicates that immunohistochemical staining with the BCOR antibody has high sensitivity for BCOR-rearranged sarcomas and is a useful diagnostic marker for BCOR-rearranged sarcomas.
BCOR-ITD sarcoma commonly occurs in infants under 1 year of age. The tumors are mainly located in the deep soft tissues of the trunk, retroperitoneum, and head and neck, less frequently involving the limbs, and include IURCS and PMMTI. Among them, PMMTI is a newly named childhood myofibroblastic tumor, of intermediate grade, with a high local recurrence rate but low metastatic potential. Histologically, it has a myxoid stromal background and needs to be differentiated from other mesenchymal tumors, such as congenital infantile fibrosarcoma, fibromyxoid sarcoma, myofibroblastic sarcoma, and dermatofibrosarcoma protuberans.
BCOR-ITD sarcomas often diffusely express BCOR. French scholar L Mardi et al. studied 341 cases of pediatric tumors of different subtypes, including 9 cases of BCOR-ITD sarcoma and 332 cases of non-BCOR genetic alteration tumors such as gliomas and ependymal tumors. IHC results showed that BCOR-ITD sarcomas all diffusely expressed BCOR, while all 332 non-BCOR genetic alteration tumors were negative for BCOR. The sensitivity and specificity of BCOR staining for BCOR-ITD both reached 100%, indicating that BCOR is a reliable marker for the diagnosis of BCOR-ITD sarcoma.
Clear cell sarcoma of the kidney
Clear cell sarcoma of the kidney is the second most common renal malignancy in childhood, accounting for 4-5% of all kidney tumors. It is highly aggressive and can metastasize widely. Microscopically, the classic type (accounting for 91% of all cases) is characterized by structures composed of nests or cords of round cells with clear cytoplasm, separated by regular fibrovascular septa. An extracellular matrix rich in mucopolysaccharides contributes to giving the tumor its ‘clear’ appearance. However, this tumor is highly heterogeneous and can also exhibit various morphological features such as epithelioid, spindle cell, sclerosing, palisading, cystic, sinusoidal, pericytic, pleomorphic, and anaplastic types, posing certain diagnostic difficulties.
Five independent studies during 2015-2016 all showed recurrent internal tandem duplication (ITD) amplification abnormalities in the BCOR gene in clear cell sarcoma of the kidney, accounting for more than 75% of tumor samples. These genetic alterations lead to increased BCOR mRNA levels, which can be detected by nuclear labeling with the BCOR antibody in immunohistochemistry.
Muhammad Zeeshan Khan et al. conducted an IHC study on 27 related tumors (including 12 cases of clear cell sarcoma of the kidney, 12 cases of Wilms tumor, and 3 cases of congenital mesoblastic nephroma). The results found that BCOR staining positivity in clear cell sarcoma of the kidney was as high as 91.67% (11/12), with 10 cases showing strong nuclear diffuse staining and only 1 case showing moderate staining. All Wilms tumors and congenital mesoblastic nephromas were negative for BCOR staining. This indicates that diffuse and strong nuclear staining with the BCOR antibody is highly specific for CCSK and is a good IHC marker for diagnosing clear cell sarcoma of the kidney.
The study by Matsuyama A et al. reported that 50% of synovial sarcomas can also show BCOR-positive expression. The study by Yu-Chien Kao et al. found that monophasic, biphasic, and poorly differentiated subtypes of synovial sarcoma have higher BCOR mRNA levels and can show BCOR-positive expression.
In addition, BCOR can also show positive expression in YWHAE‑NUTM2B fusion round cell sarcoma and is a specific marker for high-grade endometrial sarcoma with YWHAE-NUTM2B fusion.
BCOR immunohistochemical staining is a highly sensitive and specific marker for BCOR-rearranged sarcoma, BCOR-ITD sarcoma, clear cell sarcoma of the kidney, YWHAE‑NUTM2B fusion round cell sarcoma, and monophasic, biphasic, and poorly differentiated subtypes of synovial sarcoma. It can be used as a useful diagnostic marker for these different molecular subgroups.。
Related antibodies from MX
|
Antibody Name
|
Product Number
|
Clone Number
|
Cellular Localization
|
|
BCOR
|
MAB-0879
|
C-10
|
Nuclear
|
References:
[1] Writing Expert Committee of ‘Expert Consensus on Immunohistochemical Detection of Soft Tissue and Bone Tumors (2022 Edition)’. Expert Consensus on Immunohistochemical Detection of Soft Tissue and Bone Tumors (2022 Edition)[J]. Chinese Journal of Pathology, 2022, 51(03):183-189.
[2] Shi Huijuan, Han Anjia. Application and new progress of new immunohistochemical antibodies in pathological diagnosis of soft tissue tumors[J]. Chinese Journal of Pathology, 2022, 51(03):177-182.
[3]Yu-Chien Kao, ,Yun-Shao Sung, Lei Zhang et al. BCOR Overexpression is a Highly Sensitive Marker in Round Cell Sarcomas with BCOR Genetic Abnormalities[J].Am J Surg Pathol. 2016，40(12): 1670–1678.
[4]Astolfi A，Michele F，Fraia M， et al. BCOR involvement in cancer. Epigenomics, 2019.11(7):835-855.
[5]Muhammad Zeeshan K,Noreen A,Usman Hassan, et al. Diagnostic Utility of BCOR Antibody in Clear Cell Sarcomas of Kidney[J]. International Journal of Surgical Pathology,2020,28(5).
[6]Matsuyama A, Shiba E, Umekita Y, et al. Clinicopathologicdiversity of undifferentiated sarcoma with BCOR‑CCNB3 fusion: analysis of 11 cases with a reappraisal of the utility of immunohistochemistry for BCOR and CCNB3[J].Am J Surg Pathol, 2017, 41(12):1713-1721.
For more information, please contact: 800-8581156 or 400-889-9853
