Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy

Breast Cancer Res Treat. 2018 Jun;169(3):447-455. doi: 10.1007/s10549-018-4717-y. Epub 2018 Feb 17.

Abstract

Purpose: Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized.

Methods: This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA).

Results: Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail.

Conclusions: This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.

Keywords: Breast cancer; Endothelium; Expression; FOLH1; Marker; PET/CT; PSMA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Biomarkers
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / therapy
  • Female
  • Gene Expression
  • Glutamate Carboxypeptidase II / genetics
  • Glutamate Carboxypeptidase II / metabolism*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Positron Emission Tomography Computed Tomography
  • Radioisotopes / therapeutic use
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antigens, Surface
  • Biomarkers
  • Radioisotopes
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II