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Prostate Specific Antigen Isoforms

Current prostate specific antigen (PSA) immunodiagnostic assays for prostate cancer (total PSA and free PSA) struggle with a 61-78% false positive rate and a 15-27% false negative rate.¹ It is now known that there are 4 isoforms of PSA (Figure):² One isoform is associated with the normal prostate, two are associated with benign prostatic hyperplasia (BPH), and one precursor to PSA (pPSA) is associated with prostate cancer. The reason for the low sensitivity and specificity of the accepted total and free PSA immunoassays is that both assays crossreact with the BPH- and cancer-associated isoforms. Immunoassays specific for the pPSA isoform have proven difficult to develop.

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¹Semjonow et. al. (2001), Clin. Chem.47:1472-1473.
²Mikolajczyk et al. (2004), Clin. Biochem. 37:519-528.