Heitkötter Birthe, Trautmann Marcel, Grünewald Inga, Bögemann Martin, Rahbar Kambiz, Gevensleben Heidrun, Wardelmann Eva, Hartmann Wolfgang, Steinestel Konrad, Huss Sebastian
Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany.
Department of Urology, University Hospital Münster, University of Münster, Germany.
Oncotarget. 2017 Jan 17;8(3):4268-4276. doi: 10.18632/oncotarget.13994.
PSMA (prostate specific membrane antigen) is physiologically expressed in normal prostate tissue. It is overexpressed in prostate cancer cells and has been suggested as a target for antibody-based radioligand therapy. As PSMA expression so far has not been systematically analyzed in soft tissue tumors, the current study aims at investigating a large cohort of different subtypes.
Immunohistochemistry was used to detect PSMA expression in 779 samples of soft tissue tumors and Ewing sarcoma as a primary bone malignancy. CD34 coexpression was employed to study PSMA expression in the neovasculature. PSMA expression was found in the tumor-associated neovasculature of 151/779 soft tissue/bone tumors (19.38%) and was more frequent in malignant tumors compared to tumors with intermediate or benign biological potential (p=0.078). Strong neovascular PSMA expression was predominantly observed in subsets of different sarcomas including 3/20 rhabdomyosarcomas (15%), 4/21 malignant peripheral nerve sheath tumors (19.05%), 6/16 synovial sarcomas (35.29%) and 6/33 undifferentiated pleomorphic sarcomas (18.18%).
We conclude that PSMA is expressed in the neovasculature of a subset of soft tissue tumors to a variable extent. Our observation of strong PSMA expression predominantly occurring in sarcomas might provide a rationale to evaluate PSMA-targeted radioligand therapy in these entities.
前列腺特异性膜抗原（PSMA）在正常前列腺组织中呈生理性表达。它在前列腺癌细胞中过度表达，并被认为是基于抗体的放射性配体治疗的靶点。由于迄今为止尚未对软组织肿瘤中的PSMA表达进行系统分析，本研究旨在调查一大群不同亚型的软组织肿瘤。
采用免疫组织化学方法检测779例软组织肿瘤样本以及作为原发性骨恶性肿瘤的尤因肉瘤中PSMA的表达。采用CD34共表达来研究新生血管中PSMA的表达。在151/779例软组织/骨肿瘤（19.38%）的肿瘤相关新生血管中发现了PSMA表达，与具有中间或良性生物学潜能的肿瘤相比，恶性肿瘤中PSMA表达更常见（p = 0.078）。在不同肉瘤亚型中主要观察到新生血管PSMA强表达，包括3/20例横纹肌肉瘤（15%）、4/21例恶性外周神经鞘瘤（19.05%）、6/16例滑膜肉瘤（35.29%）和6/33例未分化多形性肉瘤（18.18%）。
我们得出结论，PSMA在一部分软组织肿瘤的新生血管中有不同程度的表达。我们观察到PSMA强表达主要发生在肉瘤中，这可能为评估这些实体瘤中PSMA靶向放射性配体治疗提供理论依据。
