Clinical behavior of prostatic specific antigen and prostatic acid phosphatase: a comparative study

We assayed prostatic specific antigen and prostatic acid phosphatase serum levels in 1,383 patients using a double antibody radioimmunoassay (RIA) 125I. Establishing the upper normal limit in 10 ng/ml for prostatic specific antigen and 2.5 ng/ml for prostatic acid phosphatase, the false positive results were only 1.9 and 5.1% in men with nonprostatic benign or malignant pathology and 0 and 2.2% in women, respectively. We detected false positive levels in 3.5 and 4.7% of the patients with noncomplicated benign prostatic hypertrophy, 64.8 and 19.2% in complicated benign prostatic hypertrophy, 24 and 16% in acute prostatitis and 3.3% in chronic prostatitis for both tumoral markers. The sensibility in patients with prostate cancer was 87.2 and 64.1%, respectively, and there was better correlation with prostatic specific antigen than prostatic acid phosphatase levels on tumoral spread and histologic grading. Finally, the clinical efficacy was higher with prostatic specific antigen and it did not increase with the quantification of both tumoral markers.     

Serum prostatic acid phosphatase determination in prostatic diseases: a critical comparison of an enzymatic and a radioimmunologic assay

A prospective study comparing a new radioimmunologic and a classical enzymatic assay for prostatic acid phosphatase was done to evaluate their respective roles in patients with prostatic diseases. We studied 50 patients with cancer of the prostate, 101 with benign prostatic hypertrophy and 17 with prostatitis as well as patients with nonprostatic malignancy, and various hematological and bone diseases. The results showed a low incidence of elevated values in patients with early cancer of the prostate and a high incidence of false positive values with the radioimmunoassay in patients with benign prostatic diseases, especially prostatitis. These data suggest that tests for serum prostatic acid phosphatase levels remain disappointing in the assessment of prostatic disease regardless of the technique used.     

Clinical evaluation of serum gamma-seminoprotein in patients with prostatic cancer

The level of serum gamma-seminoprotein (gamma-Sm) was measured by enzyme immunoassay in 62 patients with untreated prostatic cancer and 89 patients with benign prostatic hypertrophy histologically diagnosed to assess the clinical usefulness as a tumor marker. The level of serum prostatic acid phosphatase (PAP) was also measured by radioimmunoassay in these patients simultaneously. Serum gamma-Sm levels in prostatic cancer were significantly higher than in benign prostatic hypertrophy. There was a tendency for serum gamma-Sm levels in prostatic cancer to increase with statistically significant difference as the stage progressed. A gamma-Sm level of over 5.0 ng/ml was considered to be positive. The positive rate of gamma-Sm was 56.5% in prostatic cancer (stage A.B: 32.3%, stage C: 75.0%, stage D: 90.9%) and 19.1% in benign prostatic hypertrophy. In stage A.B cases, the positive rate of gamma-Sm was higher than that of PAP. Therefore, the measurement of gamma-Sm is considered to be useful in the diagnosis of early prostatic cancer.     

Evaluation of prostate-specific antigen and prostatic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.     

Clinical evaluation of gamma-seminoprotein as a serum marker of prostate carcinoma

The serum levels of gamma-Seminoprotein (gamma-Sm) were determined by enzyme immunoassay in 77 patients with prostatic cancer (30 untreated and 47 treated), 44 patients with benign prostatic hypertrophy and 12 patients with prostatitis. Serum levels of gamma-Sm in each disease were as follows; untreated prostatic cancer 23.2 +/- 18.3 ng/ml (positive rate 93%), treated prostatic cancer 4.7 +/- 8.3 (positive rate 25.5%), benign prostatic hypertrophy 3.6 +/- 3.3 (positive rate 23.7%), prostatitis 2.0 +/- 2.0 (positive rate 7.7%). Serum gamma-Sm levels in prostatic cancer were higher in advanced stage but relatively low in poorly differentiated adenocarcinoma. We consider that the level of serum gamma-Sm is a useful tumor marker as well as prostatic acid phosphatase (PAP) in diagnosis and follow-up of the patients with prostatic cancer.     

The significance of serum gamma-seminoprotein in prostatic cancer

The level of serum gamma-seminoprotein (gamma-Sm) was determined by enzyme immunoassay using an EIA gamma-Sm test kit in 32 patients with prostatic cancer (before treatment for 12 and after treatment was started for 20), 24 patients with benign prostate hypertrophy and 22 patients with other urogenital cancer. A gamma-Sm level of over 4.0 ng/ml was considered to be positive. The positive rate was 43.8% in prostatic cancer patients (83.3% before and 20.0% after treatment), 25.0% in benign prostate hypertrophy and 0% in other urogenital cancer. Since the positive rate of prostatic acid phosphatase (PAP) was 34.3% in prostatic cancer patients (75.0% before and 10.0% after treatment) and 16.7% in benign prostate hypertrophy patients, gamma-Sm may be more sensitive but less specific as an indicator of prostatic cancer in PAP. In 9 patients with prostatic cancer before treatment, the levels of serum gamma-Sm and PAP were serially determined for up to 11 months. The level of gamma-Sm decreased in 7 patients, and PAP in all patients after hormone therapy. One patient showed a consistently positive gamma-Sm level and the level of the others became positive only for gamma-Sm during follow-up. There was a statistical correlation between the levels of serum gamma-Sm and PAP in patients with prostatic cancer (r = 0.595, p less than 0.01), in patients with benign prostate hypertrophy (r = 0.882, p less than 0.01) and also in the patients in both groups together (r = 0.590, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and pathological study of tumor marker in benign prostatic hypertrophy and incidental prostatic cancer]

To determine the value of prostatic markers for prostate cancer, serum prostatic acid phosphatase (PAP), prostate specific antigen (PSA) and gamma-Seminoprotein (gamma-Sm) were measured in 81 patients with benign prostatic hypertrophy and in 12 patients with incidental prostatic cancer. gamma-Sm was the most sensitive but the least specific of the three markers. Large prostate glands, especially hyper-glandular type tended to be associated with high gamma-Sm levels in our study. Patients with acute urinary retention, acute prostatitis and necrosis also showed positive markers. Out of 12 patients with incidental cancer, 5 patients had more than 2 elevated markers. Four patients with poorly differentiated adenocarcinoma failed to show increased markers.     

Prostatic specific antigen in the serum in prostatic cancer

Prostatic specific antigen (PA) level was determined with a Wako test kit (Japan) for prostatic cancer and others. The incidence of abnormal values of PA in untreated prostatic cancer, was 50, 50, 80, and 100% for stage A1, C (pN0, NX), D1 and D2 cancers, respectively. Grade was not related to the level of PA. Prostatic hypertrophy, prostatitis and urinary stone showed a false positive rate of 52, 18 and 0%, respectively. The level of PA was not correlated to those of prostatic acid phosphatase (RIA). In 31% of the cases, the elevated PA decreased 4 weeks after start of endocrine treatment. Elevated PA in low grade cancer was not normalized as much as that in high and moderate grade cancers. The positive rate of PA in the serum of reactivated patients was significantly higher than that of the patients with cancer under good control by endocrine treatment.     

Evaluation of prostate-specific antigen and prosttic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.     

Prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA) in prostatic cancer

The levels of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA) were determined in the serum of 200 untreated patients 28 patients with reactivated prostatic cancer and 179 patients with benign prostatic hypertrophy (BPH) from 1979 to 1987. PAP and gamma-Sm were determined using an Eiken and Chugai kit, respectively and PA was assayed using an Eiken or Travenol kit. The sensitivity of PAP, gamma-Sm and PA respectively in the untreated prostatic cancer cases was 0, 0% and 67%, for Stage A1, 25, 17 and 100% for Stage A2, 23, 50 and 60% for Stage B, 62, 81 and 94% in Stage C, 58, 67 and 90% for Stage D1, 86, 88 and 100% for Stage D2. The specificity of PAP, gamma-Sm and PA is 89, 69 and 43%, respectively. The efficiency of PAP was the highest at all stages as a whole, but when compared at each stage, gamma-Sm was the highest at Stages B and C. The sensitivity of simultaneous assays of PAP and gamma-Sm was slightly increased, but sensitivity was not increased by simultaneous use of three markers. The efficiency of a simultaneous assay was lower than that of a single assay with PAP. However, combined determination of gamma-Sm or PA with PAP was found to be useful for monitoring the clinical course of the reactivated patients. Correlation between PAP and PA levels was high, but that between gamma-Sm and PA levels was low. There was no correlation between PAP and gamma-Sm levels. In conclusion, PAP is the most valuable marker for prostatic cancer, and gamma-Sm is of value for use in combination with PAP. However, an additional PA assay was not found to be of advantage.     

Local prostatic hyperthermia in the therapy of urinary obstruction caused by prostatic adenoma. Experimental, clinico histologic and structural findings]

A specifically designed system of selective prostate heating was used to treat 197 patients with prostatic diseases: 164 benign prostatic hypertrophy cases, 14 prostatic adenocarcinoma cases, 19 chronic abacterial prostatitis cases. Ninety-one benign prostatic hypertrophy patients could be evaluated at the three month follow-up date. Sixty-eight patients complained of severe obstructive symptoms and 23 had an indwelling catheter. Prostates were heated up to 42 +/- 0.5 degrees C during 60 minute long sessions, once or twice a week for five weeks. Local prostatic hyperthermia determined a marked amelioration of the clinical picture in 67% of patients who presented without an indwelling catheter. Sixteen patients (70%) were weaned off the catheter. Major complications were not encountered.     

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.     

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.     

Role of gamma-seminoprotein (gamma-SM) and prostatic acid phosphatase (PAP) as tumor markers of prostatic cancer

Between June, 1986 and December, 1987, the serum gamma-Sm and PAP was measured in 29 men with untreated prostatic cancer, 45 with treated prostatic cancer (32 were well-controlled and 13 poorly controlled), 82 with benign prostatic hypertrophy and 10 with other urological diseases. All of the patients with prostatic cancer had histologically proven disease. Enzyme immunoassay for gamma-Sm and radioimmunoassay for PAP were used. The cut-off value for gamma-Sm was 4 ng/ml and that for PAP was 3 ng/ml. The mean values of gamma-Sm and PAP were statistically high in the untreated group and also in poorly-controlled group. In the untreated group, the rate of positivity for gamma-Sm and for PAP were 69% respectively and 83% of the patients had elevated values for either or both of these markers. In clinical stage A and B, gamma-Sm and PAP values were within the normal limit, however the concentrations of mean gamma-Sm and PAP correlated well with the stage of disease. In the poorly-controlled group, positive gamma-Sm values were detected in 75% and PAP in 67%, whereas almost all of the patients had normal values for these markers in the well-controlled group. In prostatic hypertrophy, elevated gamma-Sm values were detected in 15% and elevated PAP values in 6%. After the onset of treatment, elevated values were normalized in 66.7% of the patients for gamma-Sm and in 68.4% for PAP. In the untreated group, gamma-Sm tended to show a more prompt response. In the ill-controlled group, gamma-Sm and PAP returned to normal in 50% of the patients. gamma-Sm and PAP values were well correlated with the course of the prostatic cancer and the clinical usefulness became more obvious with a combination of these markers.     

An evaluation of prostate specific antigen in prostatic cancer

Prostate specific antigen levels were measured in 118 patients with prostatic cancer and 138 control individuals. Prostate specific antigen was sensitive in detecting prostatic cancer. The levels of prostate specific antigen were elevated in 10 per cent of the patients with stage A, 24 per cent with stage B, 53 per cent with stage C and 92 per cent with stage D disease. However, prostate specific antigen levels also were elevated in 9 per cent of the patients with benign prostatic hypertrophy. This lack of specificity in the presence of benign prostatic hypertrophy probably precludes prostate specific antigen from being recommended as a screening test for prostatic cancer. The ultimate role of prostate specific antigen might be as the marker of choice to monitor therapy for prostatic carcinoma.     

Prostatic cancer after transurethral resection for benign prostatic hypertrophy]

Five cases of prostatic cancer developed after transurethral resection of prostate for benign hypertrophy are reported. Duration of transurethral resection of prostate (TUR-P) to diagnosis of prostatic cancer ranged from one year and seven months to seven years and two months, on average four years and seven months and frequency of prostatic cancer after TUR-P was estimated at 1.2%. Four of five patients complained of macroscopic hematuria. The cystourethrogram showed the mass protruded in the dilated prostatic urethra or bladder-neck in four patients (80%), a remarkable finding, and four cases were at stage D. Risk of development of prostatic cancer is not decreased even after prostatectomy and prostatic carcinoma diagnosed after TUR-P often advances in stage. Therefore, periodical examinations of the patients who had a prior prostatectomy are very important.     

Prostate specific antigen in serum of the patients with prostatic cancer

The serum prostate specific antigen (PA) was determined with the Diagnostic Products Cooperation (DPC) PSA double antibody radioimmunoassay kit. The upper limit of the normal range was set at 4 ng/ml which was the mean + 3S.D. for males over 50 years old in a mass examination. For comparison, prostatic acid phosphatase (PAP), and gamma-seminoprotein (gamma-Sm) were determined using an Eiken kit and Chugai kit, and PA was also assayed using another kit (Eiken, Travenol). Positive rate of PA and PAP in the untreated prostatic cancer was 75 and 33% in Stage A, 100 and 0% in Stage B, 100 and 100% in Stage C, 100 and 67% in Stage D1, 100 and 80% in Stage D2 and 73 and 33% in benign prostatic hypertrophy (BPH), respectively. The level of PA determined during the follow-up of prostatic cancer showed the usefulness of simultaneous PA and PAP assays for monitoring the clinical course. The PA level using a DPC kit was highly correlated to that of PA using other kit, but the correlation with gamma-Sm and PAP was low. These results show that the DPC kit is useful for determining PA, and determination of PA and PAP is of great value both in diagnosis and in the follow-up of prostatic cancer, but the high positive rate in BPH remains a problem.     

Prostate-specific antigen in prostatic pathology

Prostate-specific antigen (PSA), like prostate acid phosphatase (PAP), are prostate tissue markers that are useful in prostate disorders. Increased PSA levels are often seen in carcinomas of the prostate, but have also been reported in benign inflammatory disorders of the prostate. We therefore studied PSA levels in 600 patients aged 22 to 89 years to evaluate the usefulness of this marker in prostate disorders. The 600 patients were divided into four groups: 120 normal subjects, 180 patients with carcinoma of organs other than the prostate, 75 patients with carcinoma of the prostate, and 225 patients with benign hypertrophy of the prostate. Results: a significant difference in PSA levels was found between carcinomas and adenomas of the prostate, as well as between stage A carcinomas and adenomas of the prostate. Conversely, non significant difference was evidenced between stage A carcinomas and benign prostatic hypertrophy with inflammation. Rather than a specific marker for cancer, PSA indicates the presence of active prostatic disease, other investigations being necessary to determine whether this disease is malignant. PSA remains extremely useful for monitoring prostate carcinoma patients, especially following radical prostatectomy.     

Change in the ratio of free-to-total prostate-specific antigen during progression of advanced prostate cancer.

BACKGROUND: The ratio of free-to-total prostate-specific antigen (PSA) is different in benign prostatic hyperplasia and in the early stage of prostate cancer. The present study was undertaken to examine the ratio of free-to-total PSA in the advanced stage of this cancer and its subsequent change during course of the disease. METHODS: Free and total PSA were measured in sera collected from the following patients with benign and cancerous prostatic diseases: 47 cases of benign prostatic hypertrophy, nine in TIC with less than 10 ng/mL of total PSA, 11 in stage C, 16 in D2, 22 in remission under endocrine therapy, and 12 in relapse. In addition, PSA was measured sequentially in four other patients who were also in relapse. RESULTS: The ratio of free-to-total PSA was similar in early and advanced stages of untreated prostate cancer and was lower than that in benign prostatic hyperplasia. The ratio increased to the level of benign prostatic hyperplasia during remission from stages C and D2 under endocrine therapy. There was no correlation with the intervals from the start of the therapy to examination. Following relapse, the ratio came down gradually to the level obtained in untreated prostate cancer. CONCLUSION: The ratio of free-to-total PSA was similar in all stages of untreated prostate cancer. Response and relapse to endocrine therapy were associated with increase and decrease in ratio, respectively.     

The significance of serum prostate-specific antigen, gamma-seminoprotein and prostatic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hyperplasia (BPH), chronic prostatitis and acute prostatitis. PA has proved to be diagnostically more sensitive than PAP and gamma-Sm for the detection of prostatic cancer. Although PA may be elevated more frequently than PAP and gamma-Sm in patients with BPH, there are possibilities that these patients with elevated PA and normal PAP and gamma-Sm may have prostatic cancer or precancerous conditions not detectable in our routine diagnostic procedures. We report two cases of prostatic cancer with persistently elevated PA and diagnosed after repeated biopsies. Our data suggest that PA is a sensitive and useful tumor marker for the diagnosis of prostatic cancer. PAP and gamma-Sm in combination with PA may serve as more useful for differential diagnosis and confirmation of prostatic cancer.