Elevation of serum prostatic acid phosphatase levels after prostatic massage

The effect of prostatic massage on the serum prostatic acid phosphatase (PAP) levels determined by radioimmunoassay (RIA) was studied in 29 patients with benign prostatic hyperplasia (BPH) and 7 patients with prostatic carcinoma (CA). Among the BPH patients, 77 per cent (P less than 0.001) showed an increase in post-massage PAP levels but only 3 (10%) showed an increase to more normal levels.     

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.     

Serum acid phosphatase levels following prostatic massage (author's transl)]

We find an elevation of serum acid phosphatase levels 5 min after prostatic massage in only 10% of patients with prostatic adenoma. This increase is caused by stored prostatic secretion being pressed into the blood vessels. 60 min later these serum levels decrease. With some other patients a slower increase of phosphatase levels occurs; this increase, however, lasts for hours. This kind of increase is caused by prostatic fluid being forced into the interstitium where it is slowly absorbed. A combination of both kinds leads to a curve with two peaks; this could be demonstrated in two cases. No difference was seen in reaction of total acid phosphatase and prostatic phosphatase levels. The increase of phosphatase levels following prostatic massage was no sign of prostatic carcinoma.     

Counterimmunoelectrophoretic studies of serum prostatic acid phosphatase

A counterimmunoelectrophoretic (CIEP) assay for the specific determination of prostatic acid phosphatase (PAP) is described. PAP was obtained from benign human prostatic tissue and a specific antiserum to this enzyme was produced in rabbits and goats. The lowest detectable activity of PAP was at 0.3 IU/l or 4 ng./0.1 ml. This CIEP method was compared to a standard biochemical method (Roy) on a wide spectrum of prostatic and nonprostatic disease. Nonprostatic malignancies and other disorders associated with hyperacidphosphatasemia by the biochemical method were found to be nonreactive for PAP by CIEP. Patients under treatment with various stages of prostatic carcinoma showed comparable elevations by both methods (35%). In untreated patients, the CIEP was statistically most sensitive in stage A (39% by CIEP and 14% by chemical).     

Changes in serum acid and alkaline phosphatase and leucine aminopeptidase activities following massage of the prostate

The changes in serum alkaline phosphatase, total acid phosphatase, prostatic acid phosphatase and leucine aminopeptidase activities following massage of the prostate in patients with carcinoma or benign hyperplasia of the prostate having premassage control activities of a definite range were studied. Statistical significance of results was calculated by the F method. The results are as follows: 1) Following massage of the prostate the total serum acid phosphatase activity increased significantly, more markedly in benign hyperplasia than in carcinoma, and this may help to differentiate benign hyperplasia from carcinoma of the prostate. 2) Following massage of the prostate, serum alkaline phosphatase, prostatic acid phosphatase and leucine aminopeptidase activities showed no significant changes in either group.     

Cancer serum index and prostatic acid phosphatase for detection of progressive prostatic cancer

The ratio of alpha 1 acid glycoprotein/prealbumin, referred to as a cancer serum index, has been proposed as a marker for neoplastic disease. In a series of 130 patients with prostate cancer, the cancer serum index was measured along with serum prostatic acid phosphatase. A significant difference for both the cancer serum index and serum prostatic acid phosphatase was detected between those patients with no evidence of active disease after treatment and those with progressive disease after treatment.     

Solid-phase immunofluorescent and immunoadsorbent assays of serum prostatic acid phosphatase

Human prostatic acid phosphatase was purified to homogeneity from malignant prostatic tissue by Tween 80 extraction and 40-75% ammonium sulfate precipitation, followed by Con A-Sepharose, DEAE-cellulose, and gel filtration chromatography. A specific antiserum was raised by immunizing female goats or rabbits with the purified enzyme. This antiserum did not cross-react with the acid phosphatase of other human tissues. Two immunochemical methods, a solid-phase fluorescent immunoassay and a solid-phase immunoadsorbent assay, were developed. The IgG antibody fraction from antiprostatic acid phosphatase was conjugated to CNBr-activated Sepharose 4B, which was then used in the two immunoassays to separate serum prostatic acid phosphatase from other acid phosphatases or serum proteins. The enzyme activity was subsequently measured by incubating the solid-phase bound prostatic acid phosphatase with α-naphthyl phosphate and quantitating the fluorescent product with a spectrophotofluorometer (immunofluorometric assay) or quantitating the α-naphthol-FRBS colored complex with a spectrophotometer (immunoadsorbent assay). The sensitivity of this immunofluorometric assay was 60 pg/ml, more sensitive than other immunoassays. The results obtained from clinical evaluation indicate that serum prostatic acid phosphatase in prostate cancer can be detected in significant percentage with early stages of prostatic cancer. The sensitivity of the immunoadsorbent assay was 0.22 IU/l of enzyme activity or 0.88 ng of prostatic acid phosphatase protein per ml serum. Initial clinical evaluation demonstrated that 19 of 25 patients with early stages of prostate cancer and 12 of 14 patients with metastatic prostate cancer exhibited an elevated serum PAP level (over all 79%), as compared with only six and eight patients respectively (overall 35%), by a conventional chemical method.     

The significance of prostatic serum acid phosphatase as a tumor marker in prostatic cancer

The levels of prostatic serum acid phosphatase (PSAP) were determined by radioimmunoassay using RIA-Quant PAP test kit on 14 normal females, 56 normal males, 25 patients with prostatitis, 74 patients with benign prostate hypertrophy, 129 patients with prostatic cancer, 50 patients with nonprostatic malignancies, and 16 post radical cystectomized males, making 364 cases in all. To diagnose prostatic cancer, a PSAP level of over 3.0 ng/ml was determined positive for differential diagnosis of prostatitis, benign prostate hypertrophy, and prostatic cancer. According to this criterium, the positive rate for each type of disease was: 0% for prostatitis, 5.4% for benign prostate hypertrophy, 80.6% for untreated prostatic cancer, and 2% for nonprostatic malignancies. In benign prostate hypertrophy, the cases with urethral catheters showed a tendency of high PSAP level, but no significant difference was observed. PSAP positive rates of untreated prostatic cancer by stage are 0% for Stage A, 57.1% for Stage B, 85.7% for Stage C, 100% for Stage D1, and 94.1% for Stage D2 cases at a high stage showing high positive rates. However, there seems to be a limit for the diagnosis of early prostatic cancer. As for the relationship between the grade of untreated prostatic cancer and PSAP, well differentiated tumors showed higher levels of PSAP in the study with cases of the same stage. However, with all the cases, less well differentiated tumors showed higher levels of PSAP. As a tumor marker for prostatic cancer in the observation of treatment response, the PSAP level of over 2.0 ng/ml was determined positive. The relationship between the judgement of treatment response and PSAP was: Objective stable for its increase or decrease within the normal range; progressive disease for its elevation from normal to positive level, or increase or decrease of PSAP level within the positive range; Objective partial regression or objective stable for normalization from positive level. The PSAP level in the internal iliac vein of the patients with prostatic cancer tended to be higher than that in the femoral vein or antecubital vein.     

Radioimmunoassay versus counterimmune electrophoresis for measurement of serum prostatic acid phosphatase

Radioimmunoassay (RIA) kits obtained from commercial sources were evaluated and compared with a standard counterimmunoelectrophoretic (CIE) assay for the measurement of prostatic acid phosphatase (PAP) in serum. None of the radioimmunoassays was found to be more sensitive than the CIE assay in detecting elevated serum PAP. Both immunoassays were somewhat more effective clinically in measuring prostatic specific acid phosphatase than an enzyme colorimetric assay. The results obtained by CIE agreed with the results obtained by RIA in 96 per cent of the tests. The number of positive results in patients with confirmed prostate adenocarcinoma increased with disease progression. The low number of positive tests in localized adenocarcinoma (Stages A and B) suggests that neither the CIE nor any RIA procedure is useful for screening unselected populations for adenocarcinoma of the prostate.     

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.     

Combined serum and bone marrow radioimmunoassays for prostatic acid phosphatase.

Combined serum and bone marrow radioimmunoassays for prostatic acid phosphatase provide a unique means for the early diagnosis and more accurate clinical staging of prostatic cancer. The combined screening technique appears to be helpful, particularly in providing a clinical assessment of the presence or absence of early, subclinical lymphatic and bone marrow metastases. Low titer elevations of bone marrow prostatic acid phosphatase by radioimmunoassay have been observed commonly in clinically understaged C prostatic cancer with normal technetium bone scans, indicating the presence of unrecognized stage D disease with bone metastases. The combined screening method also is of distinct clinical value in the early diagnosis of prostatic cancer and in monitoring the effects of specific therapy. In therapeutically responsive patients marked suppression of serum and bone marrow prostatic acid phosphatase is observed regularly with the radioimmunochemical method under study.     

A closer look at serum prostatic acid phosphatase as screening test

Radioimmunoassay techniques for the detection of serum acid phosphatase are reported to provide substantial improvement in test sensitivity and test specificity. Calculation of the positive predictive value for this assay, however, does not support its use as a screening modality. Indiscriminate use of this test may have serious medical, psychological, and economic ramifications.     

Tissue polypeptide antigen (TPA) and prostatic acid phosphatase in serum of prostatic cancer patients

Tissue polypeptide antigen (TPA) and prostatic acid phosphatase were both detected by radioimmunoassay in the sera of a male population (age greater than 45 years) consulting the clinic for urological problems or check-up on treatment. Increased concentrations of TPA were associated mostly with advanced stages of prostatic carcinomas, parallel to PAP. Some enhanced TPA concentrations were detected with haematuria and adenomas of the prostate.