{"entity":{"id":"paper-silver-psma-expression-normal-malignant-tissues-ccr-1997","kind":"paper","name":"Prostate-specific membrane antigen expression in normal and malignant human tissues","aka":[],"tldr":"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.","asOf":"2026-09-25","links":[{"label":"Silver et al., Clin Cancer Res 1997: prostate-specific membrane antigen expression across normal and malignant human tissues by immunohistochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9815541/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["histopathology-ihc","psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling"],"terms":["ihc","theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":1997,"pmid":"9815541","authors":"Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C.","paperType":"basic","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."],"whatItMeans":"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."],"changedPractice":false},"route":"/key-papers/paper-silver-psma-expression-normal-malignant-tissues-ccr-1997/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"target":[{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"}],"pathway":[{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","route":"/pathways/prostate-cancer-signalling/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"theranostics","kind":"term","name":"Theranostics","route":"/terms/theranostics/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}],"biomarker":[{"id":"psma-pet-expression","kind":"biomarker","name":"PSMA expression by PET (PSMA-positive)","route":"/biomarkers/psma-pet-expression/"}]}}