PSMA

Synonyms: Prostate Specific Membrane Antigen

by Jan Klos

Background

PSMA is a 100 kDa transmembrane glycoprotein with folate hydrolase and neuropeptidase activity. Expressed in normal prostatic epithelium and upregulated in prostate adenocarcinoma. Despite its name it is also expressed in a subset of non-prostatic tissues and their tumors. In prostate cancer, PSMA expression has been shown to correlate with disease progression, with highest levels expressed in hormone-refractory and metastatic disease.

Staining in normal tissues

Prostate epithelium, proximal kidney tubules, salivary glands, urinary bladder, liver, esophagus, stomach, small intestine, colon, breast, fallopian tubes and testicular seminiferous tubules, hippocampal neurons and astrocytes, ependyma, cortex and medulla of the adrenal gland, ovary stroma and a subset of neuroendocrine cells in colon are positive. It has also been reported in endothelium of many non-prostatic solid tumors including carcinomas of various types (colon, breast, pancreas, kidney, urinary bladder and melanoma) but not in the vasculature of the normal tissues. Reactivity in normal seminal vesicles was not seen.

Staining in tumors

Commonly (>90%) expressed in adenocarcinoma of the prostate with lower frequency in metastatic setting, but also expressed by a subset of adenocarcinomas of stomach, small intestine, colon, pancreas, kidney, urinary bladder, lung, adrenal gland, thyroid and even mesothelioma.

Staining pattern

Staining pattern is diffuse cytoplasmic and/or membranous.

Application

  • Used in panel as additional marker supporting prostatic origin (depending on diagnostic context).
  • Promising target for diagnostic imaging and targeted radionuclide therapy of prostate cancer and its metastases.

Selected references

  1. Kinoshita Y1, Kuratsukuri K, Landas S, et al. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J Surg. 2006 Apr;30(4):628-36.
  2. Rahbar K1, Afshar-Oromieh A2, Jadvar H3, et al. PSMA Theranostics: Current Status and Future Directions. Mol Imaging. 2018 Jan-Dec;17:1536012118776068. doi: 10.1177/1536012118776068.
  3. Marchal C1, Redondo M, Padilla M, et al. Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. Histol Histopathol. 2004 Jul;19(3):715-8. doi: 10.14670/HH-19.715.
  4. Chang SS. Monoclonal antibodies and prostate-specific membrane antigen. Curr Opin Investig Drugs. 2004 Jun;5(6):611-5. Review. PMID: 15242249.
  5. Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6 Suppl 10:S13-8.