Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer

Objective:   The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.
Methods:   TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis.
Results:   Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without ( P  < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.
Conclusions:   Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.     

Comparative experimental study of the serum prostate specific antigen and prostatic acid phosphatase in serially transplantable human prostatic carcinoma lines in nude mice

Three different human lines of prostate carcinoma were successively transplanted on Balb/c nude mice and the serum values of the prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined simultaneously. In a group of the tumor-bearing animals the influence of endocrine manipulation (castration, estradiol) on the serum concentration of these tumor markers was studied. As far as untreated tumor-bearing mice are concerned, the serum values of both PAP and PSA proved to be strictly dependent on the tumor volume measured. In the exponential growth phase of the grafted tumors, linear growth was linked with a correspondingly increasing PAP and PSA serum level of the test animals. A close correlation was found to exist between the two tumor markers; however, the indicator value of PSA was 20 to 50 times higher than that of PAP under the test conditions. PSA determination yielded no false-negative results, if PAP was elevated. PAP determination was false-negative in 21 per cent of cases with measurable tumors, although the serum level of PSA already showed marked elevation. In treated animals both markers were found to decrease. Arrested growth and tumor regression was associated with falling PAP and PSA serum levels or with levels within normal range. The results of this experimental study support the conclusion that prostate specific antigen represents a substantially more sensitive tumor marker than prostatic acid phosphatase.     

Prostate-specific antigen. A new marker of prostatic pathology

Prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) were assayed using a radioimmunologic method in 306 patients from November 1986 through April 1987. Study patients included 10 women, 10 men under forty years of age, 25 patients with malignancies involving structures other than the prostate, and 280 patients with diseases of the prostate ie. benign hypertrophy of the prostate (BHP) (n = 170), or histologically-proved carcinoma of the prostate (CaP) (n = 110). Serum PSA levels were undetectable in women and following total prostatectomy; levels of 3 ng/ml were found in young men, with no circadian variations. Non-prostatic carcinomas had no influence on PSA levels. PSA levels in BHP patients were 6.9 +/- 8.4 ng/ml and correlated positively with the weight of the gland. In patients with carcinoma of the prostate, PSA levels were 24.4 +/- 19.3 ng/ml, correlated positively with tumor spread, and returned to normal following successful palliative hormone treatment, with new increases reflecting recurrences. PSA assays are of little value for screening for carcinoma of the prostate; however carcinoma of the prostate is found in 70% of patients with inconsiderable BHP and PSA levels above 15 ng/ml. PSA is mainly useful for monitoring patients with carcinoma of the prostate. No patient with BHP had marked elevations of PAP, whereas high PAP levels were found in 26% of patients with carcinoma of the prostate. Eighty-eight per cent of patients with carcinoma of the prostate had increased PAS levels, which were the only finding in 48 cases. No patient with carcinoma of the prostate had increased PAP levels with normal PSA levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

The value of the serum level of the prostate-specific antigen in prostatic pathology

Development of serum assays for prostate-specific antigen (PSA) has provided physicians with a new marker for carcinoma of the prostate. PSA was compared to prostate acid phosphatases (PAP), the reference serum marker, in 162 patients including 54 patients with carcinoma of the prostate (CP), 84 patients with benign hypertrophy of the prostate (BHP), and 24 controls free of prostate disorders. PSA appeared more sensitive but less specific than PAP. Results showed that PSA is not suitable for routine screening in the population at large where BHP is common. In BPH, the rise in PSA concentrations parallels the size of the hypertrophy. However, in patients with CP, PSA seems more sensitive than PAP for evaluating tumor spread and response to treatment. The prognostic bearing of increased levels in patients with apparently localized carcinomas remains to be elucidated.     

Relative value of prostate-specific antigen and prostatic acid phosphatase in diagnosis and management of adenocarcinoma of prostate. Ohio State University experience

Serum concentrations of prostate-specific antigen (PSA), prostate-specific acid phosphatase (PAP), and transrectal prostatic ultrasound were utilized in the evaluation of 193 men with various urologic disorders. Of the 193 patients, 48 had prostate cancer, and the other 145 included 5 with genitourinary neoplasms, 69 with benign prostatic hypertrophy, and 71 with other non-neoplastic genitourinary disease. PSA levels were elevated in 35 patients with prostate cancer and in 25 of the 145 without prostate cancer. PAP levels were elevated in 15 with prostate cancer and in 2 of the 145 without prostate cancer. The data indicate that PSA is a more sensitive but less specific tumor marker than PAP in the detection of prostate cancer. PSA appears to be more sensitive than PAP in monitoring the response to treatment. The use of PSA and PAP jointly to detect and to monitor prostate cancer did not appear to enhance the clinical utility over that of PSA alone.     

Relationship between Prostate-Specific Antigen, Clinical Stage, and Degree of Bone Metastasis in Patients with Prostate Cancer: Comparison with Prostatic Acid Phosphatase and Alkaline Phosphatase

Background:
The study was designed to examine the relation of the levels of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) to clinical stage and bone metastasis in prostate cancer patients.
Methods:
Serum PSA, PAP, and ALP levels were evaluated in 272 patients with prostate cancer. The relation of the level of PSA, PAP, and ALP to clinical stage and to degree of bone metastasis were examined by a multiple comparison method using ranks. The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic (ROC) curves. The correlation coefficients of the order of the extent of bone metastasis with PSA, PAP, and ALP were examined with Spearman's rank order correlation coefficient test.
Results:
The levels of PSA showed significant differences among 8 pairs of clinical stages, in contrast, the levels of PAP showed significant differences among 6 pairs, and the levels of ALP showed significant differences among only 4 pairs. The area under the ROC curves of PSA, PAP, and ALP for revealing bone metastasis was 84.9%, 81.4%, and 77.3%, respectively. The correlation coefficients of the order of extent of disease (EOD) with log (PSA), log (PAP), and log (ALP) were 0.346, 0.394, and 0.618, respectively, and the levels of ALP showed the most significant differences regarding the extent of bone metastasis.
Conclusion:
PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.     

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.     

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.     

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.     

Transurethral resection of the prostate in the urological management for patients with stroke]

We discuss the transurethral resection of the prostate (TUR-P) on 40 patients in the chronic stage of stroke, all of whom were refractory to conservative managements of urinary disturbance. All patients, between 35 and 89 years old (mean: 52.6 years), had only one episode of stroke and were diagnosed as benign prostatic hypertrophy or bladder neck contracture that appeared to cause urinary disturbance in these patients. At six months after TUR-P, all except for one patient, who needed an indwelling catheter due to a reinfarction, were catheter free. Of these cases 36 (92%) obtained independent micturition and did not develop urinary incontinence except transiently postoperatively. Two cases with impaired mobility and one case with progressive senile dementia required helpmates and/or a commode and so forth postoperatively. It is concluded that in chronic stroke patients TUR-P is recommended for those with benign prostatic hypertrophy or bladder neck contracture.     

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.     

PAP and PSA in prostatic carcinoma cell lines and aspiration biopsies: relation to hormone sensitivity and to cytological grading

Because a change from hormone-sensitive to hormone-resistant carcinoma of the prostate often occurs concomitantly with genetic changes or as a result of the latter, the markers specific for prostatic tissues might also be affected. We therefore first studied the presence of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in LNCaP and LNCaP-r human prostatic carcinoma cell lines. Since both markers were found in these cell lines, we proceeded to quantitate PAP and PSA in aspiration biopsies from patients with prostate tumors. The amounts of these markers were compared with cytological findings. PAP and PSA were analyzed in the biopsy material from 120 patients using commercial radioimmunoassay (RIA) kits. DNA was determined using Riedel H33258 stain. Cytological grading was performed according to the Uropathological Study Group of Prostatic Carcinoma. Significant correlations were found between PAP/DNA or PSA/DNA values and grade of differentiation of the prostate tumor. In view of earlier reports and the results presented here, the amounts of markers or the protein pattern of tumor tissue may be a useful complement to the morphological findings and for selecting optimal therapy for patients with prostatic tumors.     

Immunohistochemical demonstration of tumor-associated antigens in prostatic carcinomas of various histological differentiations

Prostate acid phosphatase (PAP), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) and keratin were determined immunohistochemically in paraffin sections from 64 prostatic carcinomas fixed in formalin according to the conventional method. The results obtained with PSA led to the correct diagnosis of prostatic carcinoma in 90.7% of the cases. 80.3% of the diagnoses obtained with PAP were correct. The intensity of the staining of the marker decreased with increasing differentiation. 3 utricular carcinomas were positive for PAP and PSA. CEA and keratin may be considered unspecific tumor markers only. However, metaplastic squamous epithelium from poorly differentiated carcinomas was always positive for keratin. PAP and PSA are also suitable for differentiating between tumors of prostatic and nonprostatic origin and could thus be successfully used to determine immunohistochemically the histogenesis of 15 invasive, poorly differentiated carcinomas of the prostate and bladder. PSA again proved to be a more specific epithelial marker than PAP.     

Adenocarcinoma of the prostate involving 2 cell types (prostate specific antigen producing and carcinoembryonic antigen producing) with selective metastatic spread.

Of 3 patients with clinically localized adenocarcinoma of the prostate 2 were treated by radical prostatectomy and 1 was treated with radiation therapy. Serum prostate specific antigen (PSA) values were elevated before therapy. After treatment the PSA levels were decreased to zero. All 3 patients later had evidence of metastatic tumor spread to the liver with elevation of serum carcinoembryonic antigen but not PSA. Immunohistochemical staining of the 2 primary tumors from the prostatectomy specimens identified 2 cell clones, one immunoreactive to PSA and prostatic acid phosphatase (PAP) and nonimmunoreactive to carcinoembryonic antigen, and the other immunoreactive to carcinoembryonic antigen but not PSA or PAP. Biopsy of a hepatic metastasis in 2 patients confirmed anaplastic carcinoma of the carcinoembryonic antigen-producing cell type. Immunohistochemical staining of a lymph node metastasis identified the PSA-producing cell type only. Such results suggest selective metastatic spread of each cell type to its own organ tropic site. Occasional carcinoembryonic antigen-producing prostate cancers may metastasize to the liver. Serum carcinoembryonic antigen measurements occasionally may be useful in the management of certain prostate adenocarcinoma patients.     

Comparative study of the clinical usefulness of prostate specific antigen and prostatic acid phosphatase in prostatic disease

The clinical usefulness of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) activity measurements has been compared in 45 patients with benign prostatic hyperplasia (BPH) and 132 patients with prostatic carcinoma (PC), 21 of whom had metastatic disease (MPC) and 111 of whom had intracapsular cancer. No BPH patient had increased PAP but 47% had increased PSA. Of the PC patients only 27% had increased PAP and 70% increased PSA. All of the MPC patients had increased PSA but only 62% had increased PAP. Increased PAP was found only in MPC but increased PSA was also found in BPH. In identifying PC, the predictive value of an increased PSA concentration is 83% and an increased PAP activity is 100%. On the other hand, the predictive value of a normal PSA concentration is 51% and of a normal PAP activity only 34%. As the PAP test is much less efficient than the PSA test, it should be discontinued.     

Prostate tumour markers as an aid in the staging of prostatic cancer.

Serum acid phosphatase activity (ACP), prostate specific phosphatase (PAP) and prostate specific antigen (PSA) were measured in 100 patients with prostatic cancer. The patients were divided into 4 groups: T1-2 MO, T3-4 MO and M1 patients with less than or equal to 10 or greater than 10 metastatic foci in bone scintigraphy. The mean serum ACP levels were almost identical in the T1-2 MO and T3-4 MO groups and there was no significant difference between the mean PAP values. Significantly higher PSA levels were observed in the MO patients in the extracapsular category compared with those in the intracapsular category. The mean serum levels of all 3 tumour markers were significantly higher in the M1 than in the MO category. PSA seems to be the marker of choice as a diagnostic aid for differentiating between patients with intracapsular and those with extracapsular tumour growth. In prostatic cancer patients with bone metastases these markers were of similar value for staging the disease.     

Changes in immunoparameters following cryosurgery in prostate cancer

To determine the effect on immunoparameters of cryosurgery in cases of stage B prostatic cancer and to determine whether such changes were specifically related to the cryosurgery technique, immunoparameters were measured and compared with cases of prostatic hyperplasia treated by transurethral resection (TUR-P). A decrease in immunoparameters was recognized in the cryosurgery group at 1-3 days postoperatively (increase in IAP, decrease in NK cell activity, decrease in lymphocyte blastogenesis reaction to PHA). The protein histograms, immunoglobulin and IAP changed similarly after the two above procedures. These changes were thought to be due to the invasive nature of the procedures. However, some difference was seen between the cryosurgery group and the TUR-P group in terms of rate of lymphocyte blastogenesis reaction to PHA and Con A, IgG, complement and NK cell activity which might indicate a specific effect of cryosurgery different from TUR-P.     

Prostate specific antigen--a screening test for prostatic cancer?

A series of 287 patients referred by their family doctors with symptoms of bladder outflow obstruction were asked to attend the hospital for "pre-clinic" screening for carcinoma of prostate (CaP). Blood samples were collected from 211 patients and analysed for serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Thirty-six patients had a serum PSA greater than 10 micrograms/l and 7 had PAP levels greater than 5 iu/l. In no instance was the PAP elevated without an associated increase in PSA concentration. Patients with raised markers underwent further investigations which included prostatic biopsy and/or resection; 17 patients were proved to have carcinoma of the prostate, 9 of whom had distant metastases. The specificity of PSA for detecting prostate cancer in this study was 90% with a sensitivity of 89.5%, in contrast to values for PAP of 100% and 36.8%. The routine use of PAP as a marker for prostatic cancer should be abandoned. The use of PSA as a screening test in a group of patients with prostatism appears justified, but with a positive predictive value of only 47%, its use in a mass unselected screening programme is not recommended.     

Immunoperoxidase localization of prostatic antigens. Comparison of primary and metastatic sites

Immunoperoxidase staining for prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) help to identify patients with prostatic carcinoma presenting as metastatic disease from an occult primary source. To clarify further the reliability of these prostatic tissue antigens, we have examined the primary tumor and metastatic sites in 16 autopsy cases. Eleven of these had diffusely positive findings for PSA and PAP in the primary and all metastatic sites, and 1 case lacked both antigens in all locations. Four cases demonstrated variability between these antigens and among various sites. Prostatic primary lesions contained PAP and PSA in 13 (81%) and 12 (75%) cases, respectively. The most reliable metastatic sites were lymph nodes, seminal vesicles, lung, bone, and kidney; while liver, adrenal, and colorectal sites were less reliable. No relationship existed between serum PAP levels and tissue detectability of PAP. The use of both PAP and PSA increases the likelihood of properly identifying the prostate as the organ of origin of metastatic disease. In spite of the use of both markers, however, three primary lesions would have been misdiagnosed, and 1 case lacked both antigens in all metastatic sites as well. In poorly differentiated lesions, the lack of both antigens does not unequivocally eliminate the possibility of prostatic carcinoma.     

Prostatic cancer developing after transurethral resection of the prostate for benign prostatic hyperplasia

From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.