PROSTATE-SPECIFIC ANTIGEN SUPERIOR SERUM MARKER FOR PROSTATIC CARCINOMA J. A. Heaney*, Marion A. Allen, T. Keane and M. J. Duffy The Departments of Urology and Nuclear Medicine, St. Vincent's Hospital, Elm Park, Dublin 4. Summary A NEW immunoradiometric assay based on a dual monoclonal antibody reaction system (Hybritech-TANDEM R) was used to measure serum levels of prostate-specific antigen (PSA) and pros- tatic acid phosphatase. (PAP) in 39 patients with prostatic carcinoma (CAP), in 57 with benign prostatic hyperplasia (BPH) and in 14 without prostatic disease. Serum PSA was elevated in 82% of patients with CaP while PAP was elevated in only 54%. In this and other studies, PSA is super- ior to conventional serum markers in sensitivity, prediction of CaP stage and in longitudinal monit- oring of disease. A 16% false positive rate precludes PSA as a screening test. The assay used was found to be simple and reliable. Introduction For almost 50 years, serum acid phosphatase (AP) has been used as a marker in the manage- ment of patients with carcinoma of the prostate (CAP). Conventional enzymic and immunologic assays provide reasonable organ specificity but lack adequate sensitivity and tissue specificity to act as cancer screening tests in an elderly male population with a high incidence of benign pros- tatic hyperplasia (BPH) 1 In 1979, Wang 2 identified a cytopta'~nic glycopro- tein, which is produced by acinar and ductal epith- elium and secreted in prostatic fluid. This prostate- specific antigen (PSA) was detected in the serum of most patients with CaP using polyclonal im- munoassays, suggesting potential as a marker in CaP 3. As monoclonal antibodies offer the possibil- ity of even more-specific assays, we evaluated the use of PSA as measured by a dual monoclonal antibody-based immunoradiometric assay (IRMA) in patients with CaP and compared it with prostatic AP (PAP) measured by a similar assay. Materials and Me~hods Patient Population (Table I) One hundred and ten men (aged 59 to 84 years) admitted tD the Urology service had venous blood drawn for assay of serum PAP and PSA. Ninety-six Address correspondence to : Michael J. Duffy, Ph.D., Department of Nuclear Medicine, St .Vincent's Hospital, Elm Park, Dublin 4, Ireland. * Present address: Section of Urology, Department of Surgery, Dartmouth-Hitchcock Medical Center, 2 Maynard Street, Hanover, NH 03756, USA. had symptoms of prostatic obstruction or acute retention and subsequently underwent transure- thral prostatic resection or open prostectomy. Histology of the resected specimen reveraled BPH in 57 and CaP in 39. Patients with CaP were staged further by chest radiograph and bone scan. Metastases were. not demonstrated in 22 patients; disease, was intracapsular (To to T=) in 12 and extracapsular (T~,T,) in 10. Metastases (M+) were present in 17 patients. Of 14 patients without prostatic symptoms, 7 had primary bladder carcinoma, and 7 required in- guinal or scrotal surgery for benign indications. Assay Procedure Serum samples were assayed in duplicate using commercial "sandwich" IRMA kits (TANDEMR-PSA and TANDEMR-PAP) manufactured and supplied by Hybritech, Inc., 11095 Torreyana Road, San Diego, CA 92121. Each kit contained the following materials: 1) two different monoclonal mouse IgG antibodies directed against separate antigenic sites on the PSA or PAP molecule. One antibody was coated on 5/16-inch beads, and the second antibody was 1251-labeled and in buffered saline containing human serum and 0.1% sodium azide; 2) PSA or PAP calibrators-lyophilyzed, containing human serum and sodium azide; 3) washed con- centrate, 18 ml, containing 0.3% sodium azide; and 4) controls for the ass~ry, which were not lyo- philysed. The principle of the TANDEM R IRMA is the incubation test serum with the solid phase anti- TABLE I Relationship of d;iseasewith elevation of serum PSA and PAP. PSA PAP No. of >10ng/ml >2ng/ml Disease state patients No. ( % ) No. ( % ) Benign prostate hyperplasia 57 9(16) 7(12) Prostatic carcinoma 39 32(82) 21 (54) To-T2 12 7(58) 2(17) T3-T, 10 8(80) 3(30) M-t- 17 17(100) 16(94) Bladder carcinoma 7 0 0 Other* 7 0 0 *No significant urological disease. 138