A solid phase radioimmunoassay for prostatic acid phosphatase

The sensitivity of a recently developed solid phase radioimmunoassay for human prostatic acid phosphatase was compared to that of an enzymatic method using p-nitrophenylphosphate as substrate. In 109 histologically verified untreated stages I to IV prostatic cancers and 200 men without such cancer the solid phase radioimmunoassay method demonstrated substantially greater sensitivity and specificity than the enzymatic technique. In the 109 prostatic malignancies the immunochemical method correctly classified 80 (73 per cent) versus 34 (31 per cent) for the p-nitrophenylphosphate enzymatic technique (p less than 10(-6). In 44 stages I and II cancers confined to the prostate the radioimmunoassay was abnormally elevated in 19 (43 per cent) with only 4 (9.1 per cent) enzymatic elevations (p less than 10(-3). In 65 stages III and IV extraprostatic cancers correct classifications were noted in 61 (94 per cent) of the radioimmunoassays and 30 (46 per cent) enzymatic tests (p less than 10(-6). The radioimmunoassay in 200 male controls yielded 11 (5.6 per cent) and the p-nitrophenylphosphate enzymatic test yielded 7 (3.5 per cent) falsely positive results. In 90 non-prostatic human cancer sera 85 (94.5 per cent) were correctly classified as negative by the radioimmunoassay for prostatic acid phosphatase versus 66 (73 per cent) as negative by the enzymatic method. These data are discussed in terms of the merits of a radioimmunochemical approach for the measurement of human serum prostatic acid phosphatase.     

Monoclonal antibody-based radioimmunoassay compared with conventional enzyme immunoassay in the detection of prostatic acid phosphatase

Determination of serum prostatic acid phosphatase by a monoclonal antibody-based radioimmunoassay (RIA) was compared to a polyclonal antibody-based enzyme immunoassay (EIA) to study the clinical value of both test systems. The 97.5 percentile of 48 patients with histologically proven benign prostatic hyperplasia (BPH) was chosen as the normal range. The classification of 38 patients with prostatic carcinoma (CaP) stage pT1-3N0-3M0 was performed by radical prostatectomy and/or pelvic lymph node dissection. Elevated prostatic acid phosphatase (PAP) serum concentrations were observed in 1 of 26 patients with CaP stage pT1-3N0M0 by the EIA and in 7 of 12 patients with CaP stage pT1-3N1-3M0 in both assays. Distant metastases observed in 15 patients lead to elevated PAP serum concentrations in 12 patients by the RIA and in 13 patients by the EIA. The correlation coefficient of both test systems was 0.97. These data indicate that the determination of PAP by a monoclonal antibody-based RIA is of no advantage compared to polyclonal antibody-based EIA, though both test systems are suitable for the follow-up of patients with CaP. Early recognition of CaP, however, is not possible by these two test systems. Elevated serum concentrations of PAP in both assays indicated metastatic disease. These findings should be considered if a curative treatment of CaP is planned.     

Clinical assessment of solid phase immunoadsorbent assay of human prostatic acid phosphatase

A new solid phase immunoenzyme assay for human prostatic acid phosphatase was tested in clinical practice. Clearly elevated levels of prostatic acid phosphatase (PAP) were found with advancing age and even more so in patients with benign prostatic hyperplasia (BPH). In patients with localized carcinoma of the prostate there was no elevation of levels above those observed in patients with BPH. When lymph node metastases were found at staging lymphadenectomy, the preoperative level of prostatic acid phosphatase was elevated in 7 of 12 cases. Good response to hormone treatment of metastatic carcinoma of the prostate was indicated by decrease of PAP-levels to normal. Rising levels often preceded the clinical manifestation of progression.     

Evaluation of a monoclonal antibody-based enzyme immunoassay (IQ(Bio) PAP-AELIA kit) for prostatic acid phosphatase

The clinical application of enzyme immunoassay (EIA) for prostatic acid phosphatase (PAP) is reported. PAP concentration was measured by an IQ(Bio)PAP-AELIA kit. Serum samples were collected from 20 healthy individuals, 31 patients with benign prostatic hypertrophy, 14 patients with prostatis, 23 patients (47 samples) with prostatic cancer and 29 patients with various other malignancies. The coefficients of variation (%CV) in intraassay and interassay ranged from 2.3 to 4.4%, and from 3.0 to 3.6%, respectively. The recovery rate in the dilution test and recovery test were 106.2 +/- 8.9% and 101.3 +/- 6.9% respectively. A significant correlation (r = 0.994, p less than 0.01) was observed between EIA and RIA methods in the prostatic cancer patients. PAP concentration was elevated above 2.0 ng/ml in 0/2 (0%) of the treated patients with stage B prostatic cancer, 1/5 (20%) of those with stage C, 6/16 (38%) of those with stage D, and in 4/5 (80%) of the untreated patients with stage D prostatic cancer. False positive results were seen in 2/31 (6%) of the patients with benign prostatic hypertrophy, 3/14 (21%) with prostatis and 3/29 (10%) of the patients with various other malignancies. In the majority of the false positive cases, elevated levels were only just above the normal value. In conclusion, the PAP level measured by this EIA kit was correlated with the clinical response to hormone therapy for prostatic cancer.     

Enzyme immunoassay of prostatic acid phosphatase after prostatic examination. Correlation with prostate size and immunopathology

Variation in serum prostatic acid phosphatase (PAP) after prostatic digital examination was studied in 22 patients, 18 with benign prostatic hyperplasia (BPH), and 4 with prostatic carcinoma. Serum PAP was determined by enzyme immunoassay (EIA) and compared with standard enzymatic assay (EA). Prostatic tissue from transurethral resection (TUR) was subjected to routine pathologic examination and stained for PAP. PAP level increased above reference range and up to several-fold in 12 of 22 patients (54.5%) by EIA and in 22.7 percent by EA. The increase in PAP correlated positively with the prostate size estimated by digital palpation (R = 0.82, P less than 0.001). There was no definite correlation between the histologic parameters studied and the increase in PAP. No day-to-day variation in PAP level was detected in 8 other patients when samples were taken at 7 AM for three successive days. For proper comparison of PAP value, we suggest that sampling time should be fixed and specimens should be taken before prostatic manipulation.     

Radioimmunoassay for prostatic acid phosphatase in early prostatic carcinoma

A radioimmunoassay procedure has been used to measure prostatic acid phosphatase in the serum of 46 patients with intracapsular carcinoma of the prostate. The results obtained did not differ significantly from those obtained in a control group of similar size. It is concluded that the radioimmunoassay procedure for measurement of prostatic acid phosphatase has no advantage over enzyme activity measurements for the detection of early prostatic carcinoma.     

Current experience with radioimmunoassay techniques for prostatic acid phosphatase

Data are presented demonstrating that radioimmunoassay techniques for measurement of serum prostatic acid phosphatase are more sensitive than enzymatic methods in the detection of all stages of prostatic cancer. The possibility of using a solid phase RIA technique to screen for prostatic cancer is considered. Sixty-three hundred and twenty men over age 45 entering a clinical laboratory for any indication were evaluated using the RIA test for PAP. In this group 444 (7%) had elevated test values. Clinical recall and urologic review of the patients with elevated test results yielded 67 who were suspect for prostatic cancer, of whom 59 (88%) were confirmed by prostatic needle biopsy. These data suggest that the RIA for prostatic acid phosphatase as an isolated clinical procedure is not sufficiently specific to be used for screening due to the large number of false-positive results. However, the RIA-PAP test in combination with a follow-up urologic examination is quite specific and deserves further consideration as a screening method for prostatic malignancy.     

Radioimmunoassay (RIA) for prostatic acid phosphatase in patients with prostatic carcinoma

Summary In recent years radioimmunological measurements of prostatic acid phosphatase have been proposed for the diagnosis, follow-up and prognosis of prostatic carcinoma. The possibility of screening male populations at risk has even been suggested. The present paper deals with the current position of this method. We studied the specificity and sensitivity of the radioimmunoassay (RIA) for prostatic acid phosphatase in three groups of patients: a normal population, patients with benign prostatic hyperplasia, and patients with untreated prostatic carcinoma. The conclusions of this study are that the RIA is a specific method but the sensitivity is much too low to use the RIA for diagnosis and screening of patients. Comparison with the enzymatic method indicates that under good laboratory conditions the latter is preferable except for patients with metastatic disease and normal enzymatic acid phosphatases.     

Value of commercial enzyme immunoassays in the determination of prostatic acid phosphatase

In 261 non-selected patients (190 prostate adenoma, 71 carcinoma of prostate) prostatic acid phosphatase (PAP) was measured prior to treatment using three different commercial enzyme immuno assays. According to the normal values given by the manufacturers we found different specificities (ranging from 0.61-0.88) and sensitivities (0.45-0.75). However, the receiver-operating-characteristics-curves (ROC) for each of the tests were similar. Since we observed a considerable overlapping of PAP-activity measured in patients with prostatic adenoma and carcinoma we tried to optimize the specificity of the three assays. The actual cut-off value was determined by use of a tangent with the "a posteriori prevalence" (adenoma:carcinoma = 190:71 = 2.6) on each ROC-curve. With this method we found a similar range of sensitivity (0.38-0.48) and specificity (0.96-0.97). The use of a cut-off-value according to the "a posteriori prevalence" results in optimizing of sensitivity and specificity by taking into account the specific long term distribution of prostate adenoma/carcinoma in the respective material.     

Value of new fluorescent immunoassay for human prostatc acid phosphatase in prostate cancer

A new solid phase fluorescent immunoassay for human prostatic acid phosphatase in prostatic cancer has been evaluated. This technique is rapid, quantitative, and sensitive. In more than 133 patients studied by the National Prostatic Cancer Project, positive results were obtained in patients with localized, nonmetastatic disease as confirmed by clinical testing, surgical staging, and careful inspection of all pelvic lymph node material in appropriate cases. That this can occur even in Stage A₂ patients may alter current concepts on the staging or, even further, on the therapy of prostatic cancer.     

Immunohistochemistry of prostatic acid phosphatase

The human prostatic acid phosphatase is a specific marker for the prostatic epithelial cells. By using an immunoperoxidase staining method for this enzyme, it is possible both to identify the prostatic epithelial cells and to recognize the prostatic origin of metastatic lesions of prostate cancer. Of the tissues containing prostatic epithelial cells from 120 patients, positive staining reaction was detected in 114 (95%), and negative in 6. In nonprostatic tissues from 242 patients, weak but positive staining reaction was detected in 8 (3.3%), including tissues from one renal cell carcinoma and 7 breast carcinomas. Of 27 patients in whom tumor tissues were tested at a time when tumor origin was unknown, the staining reaction was positive in 14 patients later found to have prostate cancer. It was negative in 6 patients with nonprostatic carcinoma and 7 patients with carcinoma of unknown primary. Although this immunohistochemical technique for prostatic acid phosphatase appears promising in diagnosing metastatic prostate cancer, its clinical significance and limitations remain unclear, and there are considerable technical problems yet to be solved. These problems are best approached by joint collaborative efforts of the various investigators interested in prostate cancer.     

Lack of value of radioimmunoassay for prostatic acid phosphatase as a screening test for prostatic cancer in patients with obstructive prostatic hyperplasia

We examined the incidence of prostatic cancer in patients with an elevated radioimmunoassay for prostatic acid phosphatase and clinical benign prostatic hyperplasia on digital rectal examination. Of 295 patients screened with prostatic acid phosphatase tests 17 fulfilled the criteria of having an elevated prostatic acid phosphatase, clinically benign prostate and histological examination of the prostatectomy specimen. None of the 17 patients had histological evidence of prostatic cancer. The results confirm the predictions of mathematical models that prostatic acid phosphatase is of no practical value as a screening test for prostatic cancer in patients with clinical benign prostatic hyperplasia.     

Immunohistochemical prostatic acid phosphatase level as a prognostic factor of prostatic carcinoma

To determine whether prostatic acid phosphatase (PAP) immunoreactivity in prostatic adenocarcinoma is a reliable prognostic factor, the PAP immunohistochemical distribution has been examined in 78 prostatic carcinoma cases. The intensity of PAP immunostaining was graded from 0 to 2, and the scores of the primary and the secondary staining patterns were added to assess the extent of the PAP expression in needle biopsy specimens. As a result, a higher cancer-specific survival rate was observed in patients showing a greater PAP immunostaining (P less than 0.01). Further, a multivariate analysis was made of possible prognostic factors (age, stage, Gleason score, serum PAP, PAP-immunostaining score, and the initial treatment) to estimate the extent of their impact on cancer-specific survival. Results have confirmed that the difference in PAP immunoreactivity is an excellent, independent prognostic factor for prostatic carcinoma.     

Primary prostatic carcinoid tumor with intracytoplasmic prostatic acid phosphatase and prostate-specific antigen

A case of prostatic carcinoid tumor with lymph node metastases is reported. The patient was a 78-year-old male who died in ventricular fibrillation. At autopsy, a 2 X 2 cm, white, irregular tumor was found in the prostate and there were several enlarged para-aortic lymph nodes. Both specimens contained a characteristic carcinoid tumor. Argyrophil stains revealed strong positivity in the primary as well as in the metastatic tumors. Electron micrographs prepared from formalin-fixed tissue demonstrated numerous membrane-bound dense-core granules. Immunoperoxidase-labeled antibodies against both prostatic acid phosphatase and prostate-specific antigen localized in the tumor cells. The ultrastructural and immunohistochemical results support differentiation of the tumor cells toward both prostatic epithelial cells and endocrine cells. We believe that this is the first reported case of a prostatic carcinoid tumor in which specific prostatic tissue markers have been demonstrated in the tumor cells.     

Immunoperoxidase localization of prostatic acid phosphatase in prostatic carcinoma with sarcomatoid changes

Immunoperoxidase staining of tissue for prostatic acid phosphatase has been useful in confirming the prostatic origin of metastatic deposits. This technique was used on the prostate tumors of 2 patients to differentiate between a true carcinosarcoma and a pure epithelial carcinoma with sarcomatoid changes. Positive staining for prostatic acid phosphatase in both the sarcomatoid element, as well as the area of well-differentiated carcinoma, confirmed the common epithelial cell origin of these components. Electron microscopy further confirmed these findings by demonstrating desmosomes in the sarcomatoid areas. Although each type of tumor is rare, differentiation between true carcinosarcomas and true carcinomas with sarcomatoid changes is important to elucidate further their different clinical behaviors and responses to therapy.     

Radioimmunoassay of serum prostatic acid phosphatase after prostatic massage

The effect of prostatic massage on the concentration of prostatic acid phosphatase (PAP) in blood serum as determined by radioimmunoassay (RIA) was compared with that determined by a standard enzymatic assay (EA). Serum was drawn from 24 men before prostatic massage and after--at specified intervals, up to twenty-four hours. Three of these men were young, normal controls; 10 had biopsy-proved prostate cancer (CA); 11 had histologically confirmed benign prostatic hyperplasia (BPH). After prostatic massage, 3 of the 10 CA patients (30%) had elevation of PAP as determined by EA and 4 of the 11 BPH patients (36%) as determined by RIA. None of the controls showed elevated levels of PAP by either assay. In all patients elevated levels of PAP by both assays had returned to normal twenty-four hours after massage. It was concluded that serum for PAP testing by either assay method should be drawn before or twenty-four hours after rectal examination to prevent false positive results and the need for retesting.     

Immunohistochemical identification of prostatic acid phosphatase: correlation of tumor grade with acid phosphatase distribution

The localization and distribution of prostatic specific acid phosphatase (PSAP) in normal, hyperplastic and neoplastic prostates were studied by specific immunohistochemical of normal and hyperplastic prostates. In adenocarcinoma of the prostate, a correlation of the PSAP staining with the degree of differentiation and the ability of the tumor to form a gland was observed: more intense and uniform staining in well differentiated tumors and less intense and more variable stains in poorly differentiated tumors. The same correlation was also observed in tumors metastasized to lymph nodes and other organs.