A prostate-specific antigen, distinct from acid phosphatase, was identified by immunologic procedures in prostate tissues (normal, benign hypertrophic, and cancerous) and seminal plasma, as well as in sera of patients with prostatic cancer and of nude mice bearing human prostatic tumor. This antigen was shown by immunoperoxidase staining to be confined to epithelial cells comprising the prostatic ductal elements. Prostate antigen was purified from prostatic tissue and seminal plasma, and it was shown to have a molecular weight of 33,000-34,000 with no subunit component. The isoelectric point of purified antigen was around 6.9, though several unpurified isomers with different isoelectric points also were observed. Serum-borne prostate antigen showed a molecular weight of 90,000-100,000 but it exhibited a molecular weight of 36,000 in the presence of sodium dodecyl sulfate. A sandwich-type, peroxidase-linked immunosorbent assay capable of detecting 0.1 ng of the antigen per milliliter of blood was developed. With this technique, serum level of the antigen was found to increase in patients with prostatic cancer as compared with normal males. The prostate-specific antigen can be a useful marker for detection of prostatic cancer.

Prostate-specific antigen (PA) has been evaluated clinically as a tumor marker of prostate cancer with the use of enzyme immunoassay (EIA). For serodetection of prostate cancer, PA was assayed in a total of 1,109 sera. From mean +/- 3 S.D. of normal controls, upper cut-off values in males were decided as 2.5 and 1.2 ng/ml in Americans and Japanese, respectively. Serum PA values in prostate cancer patients were positive in 78% of Americans and 62% of Japanese. However, in benign prostatic hypertrophy (BPH) cases, a high false positive rate of 41% was observed in Americans. Simultaneous assays of serum PA and PAP showed high sensitivity and specificity in the detection of prostate cancer. This antigen could be used, as well as PAP, for monitoring prostate cancer patients. Furthermore, serum PA levels prior to treatment may express to some degree the malignant potential of the cancer. These results suggest that PA may be useful as a tumor marker of prostate cancer.

Thus, the determination of f/t was considered to be an effective tool for discriminating the non-prostate cancer cases from those of prostate cancer.

Hybridoma culture F5 has been developed which secretes monoclonal antibody (McAb) directed to an epitope of a prostatic glycoprotein of Mr 34 kD (Prostate Antigen, PA). Tissue levels of PA have been evaluated using a competitive-binding enzyme-immunoassay based upon the inhibition of McAb binding activity to purified antigen. Results indicated the specific occurrence of high antigen concentrations in extracts prepared from prostatic tissues. The antigenicity of epitope F5 is resistant to tissue fixation and embedding protocols, and has been demonstrated upon immunoperoxidase staining procedures. Immunoperoxidase data strongly indicate that McAb F5 possesses a singular specificity towards prostatic epithelial cells. Other tissues, whether normal or cancerous, fail to express this determinant. Specimens examined included epithelial and nonepithelial tissues along with a panel of carcinomas and sarcomas. The antibody was able to detect tumor cells at extra-prostatic sites and represents a powerful probe for the detection and differential diagnosis of metastatic cancer of the prostate.

The reference values for total PSA, F/T and PSAD must be changed according to prostatic volume in order to maintain a sufficient diagnostic sensitivity of CAP. Of these parameters, PSAD showed a high specificity in the group with a prostatic volume of <40 ml.