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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Neovascular prostate specific membrane antigen (PSMA) expression in bone and soft tissue sarcoma: a systematic
Irene A Spiridon1,2, Sheena L M Ong1, Jiri Soukup1,3,4
1Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands.
Abstract:
Bone and soft tissue sarcomas are a highly heterogeneous group of rare cancers of mesenchymal origin. Treatment options other than surgery have limited efficacy due to low response rates with some exceptions. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may provide a novel treatment option, as it was recently suggested that soft tissue sarcomas express PSMA in the neovasculature, and on PET/CT imaging, multiple sarcomas have shown intense PSMA-tracer accumulation. Moreover, in prostate cancer patients, incidental PSMA uptake was seen in hemangiomas. In addition to confirming previous results in soft tissue sarcoma, the current study aims to systematically explore the expression of PSMA in bone tumors and in vascular tumors. Immunohistochemistry for PSMA was performed on a total of 706 tumors. High PSMA expression in the neovasculature was seen in 29% of the soft tissue sarcomas and 33% of the bone sarcomas. Malignant tumors showed a higher frequency of PSMA expression (score 2) as compared to benign tumors, with a high frequency in rhabdomyosarcoma (2 of 2, 100%), mesenchymal chondrosarcoma (14 of 20, 70%), undifferentiated sarcoma of bone (4 of 6, 67%) and of soft tissue (13 of 20, 65%), and osteosarcoma (46 of 81, 57%). In addition, giant cell tumor of bone displayed a high PSMA labelling in 67% of the cases. In contrast, high PSMA expression was seen in only 0-40% of the non-neoplastic vessels in vascular tumors, while 8% of them expressed PSMA in the tumor cells. Thus, with variable frequency among the different subtypes, a subset of bone and soft tissue tumors, both malignant and intermediate behavior, express PSMA and these patients may benefit from PSMA-targeting PET/CT scans or PSMA targeted radioligand therapy.
Insights
Prostate-specific membrane antigen (PSMA) is expressed in a subset of bone and soft tissue tumors. This finding suggests potential benefits from PSMA-targeted imaging and radioligand therapy for these rare cancers.
Area of Science:
- Oncology
- Molecular Imaging
- Cancer Biology
Background:
- Bone and soft tissue sarcomas are rare, heterogeneous mesenchymal cancers with limited treatment options beyond surgery.
- Prostate-specific membrane antigen (PSMA) is a promising target for radioligand therapy, particularly in prostate cancer.
- Previous studies suggest PSMA expression in the neovasculature of soft tissue sarcomas and incidental uptake in hemangiomas.
Purpose of the Study:
- To systematically investigate prostate-specific membrane antigen (PSMA) expression in a wide range of bone and soft tissue tumors.
- To confirm and expand upon previous findings of PSMA expression in soft tissue sarcomas.
- To evaluate the potential of PSMA-targeted therapies for bone and soft tissue sarcomas.
Main Methods:
- Immunohistochemistry was employed to assess PSMA expression.
- A cohort of 706 diverse tumor samples, including bone sarcomas, soft tissue sarcomas, and vascular tumors, were analyzed.
- Tumor samples were scored for PSMA expression, with a focus on neovascular and tumor cell expression.
Main Results:
- High PSMA expression in tumor neovasculature was observed in 29% of soft tissue sarcomas and 33% of bone sarcomas.
- Malignant bone and soft tissue tumors, including rhabdomyosarcoma, mesenchymal chondrosarcoma, undifferentiated sarcoma, and osteosarcoma, frequently expressed PSMA.
- Giant cell tumor of bone also showed high PSMA labeling in 67% of cases. Non-neoplastic vessels in vascular tumors exhibited lower PSMA expression (0-40%).
Conclusions:
- A significant subset of bone and soft tissue tumors, encompassing both malignant and intermediate-grade types, express prostate-specific membrane antigen (PSMA).
- These findings support the potential utility of PSMA-targeted positron emission tomography/computed tomography (PET/CT) scans for diagnosis and staging.
- Patients with PSMA-expressing bone and soft tissue tumors may be candidates for novel PSMA-targeted radioligand therapies.
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