# Prostate-specific membrane antigen expression in normal and malignant human tissues

Source: https://onco.cc/key-papers/paper-silver-psma-expression-normal-malignant-tissues-ccr-1997/  
OnCo record `paper-silver-psma-expression-normal-malignant-tissues-ccr-1997` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The survey that mapped where PSMA is found in the body, and showed it is almost nowhere except the prostate, which is what makes it safe to aim a radioactive drug at it.

## Summary

An extensive immunohistochemical analysis was performed on a panel of well-characterised normal and malignant human tissues to define the pattern of prostate-specific membrane antigen expression. Detectable levels were identified in prostatic epithelium, duodenal mucosa and a subset of proximal renal tubules, and a subpopulation of neuroendocrine cells in the colonic crypts also showed immunoreactivity; all other normal tissues, including cerebral cortex and cerebellum, had undetectable levels. Thirty-three of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases showed tumour cell staining, while 8 of 18 prostate tumours metastatic to bone expressed it. All other non-prostatic primary tumours studied had undetectable levels, but intense staining was seen in capillary endothelial cells in peritumoral and endotumoral areas of certain malignancies, including 8 of 17 renal cell carcinomas, 7 of 13 transitional cell carcinomas and 3 of 19 colon carcinomas. The decrease in immunoreactivity in advanced prostate cancer suggested that expression is linked to the degree of tumour differentiation.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Clinical Cancer Research
- Year: 1997
- Authors: Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C.
- Findings: Detectable PSMA in normal prostatic epithelium, duodenal mucosa, some proximal renal tubules and colonic neuroendocrine cells only.; Staining in 33 of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases.; Staining in only 8 of 18 bone metastases, with expression linked to differentiation.; Neovascular endothelial staining in renal, transitional and colon carcinomas.
- What it means: It is the anatomical basis for PSMA imaging and PSMA radioligand therapy, and it predicted two of the practical problems three decades early: salivary, lacrimal and renal uptake as sources of toxicity, and falling expression in dedifferentiated disease as the reason some men are ineligible for treatment.
- Caveats: A small immunohistochemical survey from 1997 with the antibodies of the time.; Eighteen bone metastases is a thin basis for the differentiation claim, although later work supports it.; It predates PET imaging entirely, so the link to scan positivity is inferred.

## Sources

- Silver et al., Clin Cancer Res 1997: prostate-specific membrane antigen expression across normal and malignant human tissues by immunohistochemistry: https://pubmed.ncbi.nlm.nih.gov/9815541/

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [PSMA PET](https://onco.cc/technologies/psma-pet/), [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/)
- targets: [PSMA](https://onco.cc/targets/psma/)
- pathways: [Prostate cancer (KEGG map)](https://onco.cc/pathways/prostate-cancer-signalling/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Theranostics](https://onco.cc/terms/theranostics/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)
- biomarkers: [PSMA expression by PET (PSMA-positive)](https://onco.cc/biomarkers/psma-pet-expression/)

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