Neovascular prostate specific membrane antigen (PSMA) expression in bone and soft tissue sarcoma: a systematic analysis

Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin, vol. 487, pp. 1299–1309

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.

Authors 12

1. Irene A. Spiridon Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center · Grigore T. Popa University of Medicine and Pharmacy

   Affiliation as printed

   Department of Pathology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Iasi, Romania

   Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands

2. Sheena L. M. Ong Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands

3. Jiří Soukup Aachen Department of Pathology, Leiden University Medical Center

   Charles University · Leiden University Medical Center · Military University Hospital Prague · University Hospital Hradec Králové

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands

   Department of Pathology, Military University Hospital Prague, Prague, Czech Republic

   The Fingerland Department of Pathology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Sokolska 581, 500 05, Hradec Kralove, Czech Republic

4. Oana-Maria Topirceanu-Andreoiu Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center · Spitalului Clinic de Urgență pentru Copii Maria Sklodowska Curie

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands

   Department of Pathology, Marie Curie Children's Clinical Hospital & OncoTeam Diagnostic, Bucharest, Romania

5. Lioe‐Fee de Geus‐Oei Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

6. Hans A. J. Gelderblom Aachen Department of Medical Oncology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands

7. Suk Wai Lam Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands

8. Inge H. Briaire‐de Bruijn Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands

9. Brendy E.W.M. van den Akker Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands

10. Linda Hijmen Aachen Department of Nuclear Medicine

    Leiden University Medical Center

    Affiliation as printed

    Department of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands

11. Károly Szuhai Aachen Department of Cell and Chemical Biology

    Leiden University Medical Center

    Affiliation as printed

    Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands

12. Judith V.M.G. Bovée corresponding Aachen Department of Pathology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Pathology, Leiden University Medical Center, Postzone L1-Q, Postbus 9600, 2300 RC, Leiden, The Netherlands. J.V.M.G.Bovee@lumc.nl