Expression of PSMA in tumor neovasculature of high grade sarcomas including synovial sarcoma, rhabdomyosarcoma, undifferentiated sarcoma and MPNST

Oncotarget. 2017 Jan 17;8(3):4268-4276. doi: 10.18632/oncotarget.13994.

Abstract

Aims: 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.

Methods and results: 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%).

Conclusion: 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.

Keywords: PSMA; neovasculature; sarcoma; soft tissue tumor; therapy.

MeSH terms

  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kallikreins / metabolism*
  • Neoplasm Grading
  • Neurilemmoma / metabolism
  • Neurilemmoma / pathology*
  • Prostate-Specific Antigen / metabolism*
  • Rhabdomyosarcoma / metabolism
  • Rhabdomyosarcoma / pathology
  • Sarcoma / metabolism
  • Sarcoma / pathology*
  • Sarcoma, Ewing / metabolism
  • Sarcoma, Ewing / pathology
  • Sarcoma, Synovial / metabolism
  • Sarcoma, Synovial / pathology
  • Tissue Array Analysis / methods
  • Up-Regulation*

Substances

  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen