Angiosarcoma of the bone (B-AS) is an exceptionally uncommon and fierce type of cancer that develops from the endothelial cells of the blood vessels located in bone tissue. Protheragen offers an integrated approach for B-AS diagnostic and therapeutic service development, starting from target identification and continuing through preclinical validation.
Overview of Angiosarcoma of Bone (B-AS)
Angiosarcoma of bone (B-AS) is an uncommon bone tumor with a very aggressive course and of neoplastic vascular origin, constituting less than one percent of all primary bone sarcomas. It predominantly occurs in men, with a peak incidence between 50 and 70 years of age. B-AS is marked by an unfavorable prognosis, and its 5-year survival is reported between 20 to 33 percent. At diagnosis, the tumor is normally associated with metastatic spread and can be unifocal or multifocal. B-AS is diagnosed and treated in a very aggressive manner due to its uncommon incidence.
Fig.1 Microscopic examination of angiosarcoma of bone. (Palmerini E.,
et al., 2020)
Pathogenesis of Angiosarcoma of Bone (B-AS)
The pathogenesis of B-AS is multifactorial, involving several complex and interrelated systems. A change in the base pair structure of DNA is a critical factor in the onset of this condition. Abnormalities in the genes CIC, PLCG1, KDR, and MYC have been studied in relation to the potential malignant change to the endothelial cells. Such changes to the genes in question may disrupt normal regulatory pathways governing cell growth and blood vessel formation. B-AS is also categorized as a spectrum of vascular neoplasms that include benign hemangiomas and more advanced malignant angiosarcomas, which may reflect a continuum of increasing aggressiveness. More studies are necessary for understanding the exact molecular mechanisms in the pathogenesis of B-AS.
Diagnostics Development for Angiosarcoma of Bone (B-AS)
Histological and Immunohistochemical Diagnosis
Histological analysis is a critical step in diagnosing B-AS. It is characterized by a macronucleolus, mitotic activity of three or more mitoses per 10 high-power fields (HPF), and fewer than five eosinophilic granulocytes per 10 HPF. These changes are seen in association with a more aggressive form of the disease. For conclusive diagnosis, IHC markers CD31, ERG, and cytokeratin AE1/AE3 are important. CD31 and ERG are endothelial markers, and cytokeratin AE1/AE3 helps in excluding other neoplastic processes. Sometimes D2-40 (podoplanin) is added to demonstrate the presence of lymphangiogenic differentiation, which connotes a more aggressive behavior of the disease.
Imaging Techniques and Molecular Testing
X-rays, CT scans, and MRIs help measure the scope of the disease and assist in planning surgery. The radiological findings usually demonstrate destructive osteolytic masses, albeit with non-specific, irregular boundaries. Although these findings are radiological in nature, they are often imprecise and require collaboration with clinic and histology data for precise diagnosis.
Testing for certain molecules and genes can detect specific changes in genes associated with B-AS, such as mutations in CIC, PLCG1, KDR, and MYC. The information gained from these tests may be useful in the creation of more precise therapies and in the detection of new therapeutic targets.
Therapeutics Development for Angiosarcoma of Bone (B-AS)
- Chemotherapy
Some activity has been noted in B-AS with chemotherapy regimens such as doxorubicin ± ifosfamide. Other newer agents like paclitaxel and gemcitabine have been studied as well. The effectiveness of chemotherapy in B-AS is still being determined. Perhaps future research will seek to develop more targeted therapies tailored to the genetic and molecular profile of B-AS.
- Targeted Therapies and Immunotherapies
Immunotherapy and targeted therapy are some of the most promising research avenues for B-AS. These therapies focus on treating specific pathways that may contribute to the disease, which may be more effective and less harmful compared to traditional chemotherapy. One of the therapies that may be useful for B-AS patients is those aimed at immune checkpoints and angiogenesis.
Table 1. Therapeutics of Angiosarcoma of Bone (B-AS).
| Therapeutics |
Mechanism |
Description |
Stage |
| Surgery |
Physical removal |
Primary therapy for localized B-AS, aiming for wide or radical margins. |
Approved |
| Radiotherapy |
High-energy radiation |
Adjuvant or palliative therapy to reduce local recurrence. |
Approved |
| Doxorubicin ± Ifosfamide |
Target rapidly dividing cells |
Used in metastatic and some localized cases. |
Approved |
| Osteosarcoma-like regimen (Doxorubicin, Methotrexate, Cisplatin, Ifosfamide) |
Target rapidly dividing cells |
Used in localized cases. |
Approved |
| Angiogenesis inhibitors |
Inhibit blood vessel formation |
Target specific molecular pathways involved in tumor growth. |
Preclinical |
| Agents targeting CIC, PLCG1, KDR, MYC |
Target specific genetic alterations |
Under investigation for B-AS. |
Preclinical |
| Checkpoint inhibitors |
Enhance the immune system |
Under investigation for B-AS. |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen provides a full spectrum of services for the development of diagnostics and therapeutics for Angiosarcoma of Bone (B-AS). Our offerings include advanced histological and immunohistochemical analysis, comprehensive molecular and genetic testing, and the creation of targeted therapies and immunotherapies. Additionally, we conduct preclinical research to assess the efficacy and safety of novel therapeutics, ensuring rigorous evaluation for potential clinical application.
Disease Models
- HOS-143B or U2OS Human CDX Models
- DLM8 Mouse CDX Models
- Stem Cell-Derived Organoids
- Chemical Induction Animal Models
- Transplant Models
Protheragen offers a broad range of services related to the diagnostics and therapeutics development of Angiosarcoma of Bone (B-AS). From genetic profiling and immunohistochemistry to the development of preclinical animal models and preclinical study design, our services are designed to meet the specific needs of researchers in this field. If you are interested in our services, please feel free to contact us.
References
- Palmerini, Emanuela, et al. "Angiosarcoma of bone: a retrospective study of the European Musculoskeletal Oncology Society (EMSOS)." Scientific Reports 10.1 (2020): 10853.
- Wang, Ben, Li-jie Chen, and Xiang-yang Wang. "A clinical model of bone angiosarcoma patients: a population-based analysis of epidemiology, prognosis, and treatment." Orthopaedic Surgery 12.6 (2020): 1652-1662.
- Verbeke, Sofie LJ, et al. "Distinct histological features characterize primary angiosarcoma of bone." Histopathology 58.2 (2011): 254-264.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
