Correlation between tissular levels of prostatic acid phosphatase and prostate-specific antigen and hormonal response of metastatic prostatic cancer

A correlation between the serum levels of testosterone and the tissular intensity of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in normal prostates has been demonstrated. In prostatic cancer patients, we studied the correlation between the percentage of neoplastic cells secreting PAP and PSA and the response to androgen deprivation, and found no relationship between them. Therefore it is not possible to predict the response to hormone therapy through the grade of tissular PAP or PSA.     

Influence of prostatic disease and prostatic manipulations on the concentration of prostate-specific antigen.

We examined the influence of different factors [benign prostatic hyperplasia (BPH), prostatic carcinoma (PCA), organ volume, weight of resected tissue, transurethral catheter] on the serum prostate-specific antigen (PSA) levels in 253 patients with BPH (n = 138; 54%) and PCA (n = 115; 46%). Only in 57.2% of the BPH patients, PSA values were < 4 ng/ml, in 74.6% < 7 ng/ml. In 108 patients with BPH, a transurethral prostatectomy was performed. PSA values correlated significantly with the sonographically determined prostatic volumes and less precisely with the weight of the resected tissue. The PSA concentration per milliliter of prostatic volume was 0.12 ng/ml, per gram of resected tissue it was 0.21 ng/ml. An incidental PCA was found in 12/108 patients (11%). The PSA values were identical with those of the total collective in regard to volume and tissue weight. In 11 patients, we examined possible alterations of the PSA values before and until 24 h after prostatic massage. Only insignificant alterations were seen, a massive increase was not found in any patient. Searching for an absolutely valid 'normal value' appears hardly appropriate. However, the usefulness of PSA is increased when the sonographically determined prostatic volume is included. A rectal examination of the prostate has no influence on the PSA value.     

Significance of examination of prostate-specific antigen and prostate-specific antigen density in patients with prostatic hyperplasia and prostate cancer

Authors investigated PSA concentration and preoperative prostate volume in 113 histologically proved BPH and 31 prostatic cancer patients. PSA concentration was measured with the Hybritech kit, the prostate volume by ultrasound with the help of an ellipse and calculated by computer. There was no correlation between the age of patients and volume of the prostate, whereas a correlation was proved between marker concentration and prostate volume (p<0.0001). The difference obtained by the correlation of the prostate volume and the PSA concentration ratio between the BPH and 31 tumorous patients (PSA density) was highly significant (0.143 vs. 0.699, p<0.001). The use of PSAD further improves the diagnostic value of PSA.     

C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer

OBJECTIVE: To further analyse the relationship of c-reactive protein (CRP) levels to prostate cancer, by measuring CRP in men with prostate cancer and benign prostatic hypertrophy (BPH), as chronic inflammation has long been linked to cancers with an infectious cause and CRP is a nonspecific marker for inflammation, associated with prostate cancer incidence and progression. PATIENTS AND METHODS: Data from 114 men, most of whom had had radioactive seeds implanted, were evaluated from November 1990 to April 2002. In addition, 27 men were included who had biopsy-confirmed BPH. CRP was assessed with an automated chemiluminometric high-sensitivity assay kit. RESULTS: There was no significant difference in CRP levels in men with localized prostate cancer or BPH but levels were significantly higher in men with bone metastases. There was also a significant correlation of CRP level with prostate-specific antigen (PSA) in those with cancer. Because PSA is correlated with disease stage, multiple linear regression was used with CRP as the dependent variable, and PSA and disease stage as independent variables. The regression was significant overall (P < 0.001) and the effect of disease stage on CRP (P < 0.001) was independent of the effect of PSA level (P = 0.001). CONCLUSION: The strong association of CRP with PSA, independent of tumour stage, suggests that inflammation might be fundamental in prostate cancer, and that chronic inflammation may be a legitimate target for prostate cancer chemoprevention and treatment.     

Value of prostate-specific antigen measurements in predicting lymph node involvement in prostatic cancer.

The preoperative serum levels of prostate-specific antigen (PA) were determined in 35 consecutive patients who had clinically localized prostatic cancer and underwent bilateral staging pelvic lymphadenectomy. When 10.0 ng/ml of PA was used as the cutoff value for lymph node staging the specificity of an elevated PA level in revealing lymph node involvement was 77% with a sensitivity of 85% and an accuracy of 80%. Only 1 of 18 (6%) patients with negative PA levels (below 10 ng/ml) and a preoperative Gleason score 2-7 tumor had metastatic lymph node disease. Among the 17 patients with positive PA levels (above 10 ng/ml) or a Gleason score 8-10 tumor, 12 (71%) had lymph node involvement. The preoperative PA level and the extent of local tumor invasion correlated strongly with each other. Our study suggests that the PA level could be a simple and objective parameter with which to predict metastatic lymph node disease if used in conjunction with the Gleason histological grade.     

Experience with prostate-specific antigen in prostatic carcinoma

A total of 71 prostatic tumour patients and 45 prostatic adenoma patients were tested for prostate-specific antigen (PSA), immunological prostatic acid phosphatase (PAP) concentration as well as serum prostatic phosphatase (SPP) and enzymic serum phosphatase. It was found among untreated patients that PSA showed the highest percentage of pathologic affection in each stage. PSA, on the evidence of clearance test in the initial days of therapy and after a follow-up period of several months, gave a good picture of the course that the disease had taken.     

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.     

Diagnostic accuracy of percent free prostate-specific antigen in prostatic pathology and its usefulness in monitoring prostatic cancer patients.

INTRODUCTION: The aim of our study was to evaluate the clinical usefulness of percent free prostate-specific antigen (PSA) [ratio of free PSA (fPSA) to total PSA (tPSA); f/tPSA] in prostatic pathology and its usefulness in monitoring prostatic cancer patients. PATIENTS AND METHODS: Our prospective study was carried out on 470 consecutive male patients referred to our outpatient urological clinic for observation. We looked for relationships between tPSA, fPSA and percent free PSA and the patient's age, prostatic volume and histologic diagnosis as assessed by prostatic biopsies or surgical specimens (benign prostatic hypertrophy, carcinoma, hypertrophy with inflammation). In all cases, we calculated the specificity, sensitivity and diagnostic accuracy of percent free PSA in the diagnosis of prostatic diseases, using cutoff values ranging from 14 to 20%. In prostatic cancer patients, we considered the relationships between the various PSA molecular forms and staging, grading and follow-up values. We also evaluated the effects of hormonosuppressive therapy on the serum markers and noted for which tPSA value percent free PSA possessed the greatest diagnostic accuracy. RESULTS: While tPSA and fPSA values appeared to be correlated with patient age and prostatic volume, percent free PSA did not show a relationship with these parameters. The specificity, sensitivity and overall diagnostic accuracy were better assuming a 16% cutoff value for percent free PSA than with other cutoff values. Prostatic inflammation associated with benign hypertrophy can cause false positives in both tPSA and f/tPSA measurements, since 60% of these patients have an f/tPSA ratio below 16%. In diagnosing carcinoma, the diagnostic accuracy of percent free PSA is 100% when tPSA is between 2.5 and 4.0 ng/ml. Percent free PSA is not linked with staging in prostatic cancer, but it does appear to be related to the Gleason score. In patients receiving hormonosuppressive treatment, f/tPSA decreased significantly, and more so in patients with a higher Gleason score. In patients with disease in rapid progression, percent free PSA was lower than in patients in a stable condition. CONCLUSIONS: Based on our experience, 16% as the f/tPSA cutoff value for discriminating between benign and malignant pathologies is the best possible choice, as it provides the highest overall values of sensitivity, specificity and diagnostic accuracy (80, 61.5 and 84.5%, respectively) in the diagnosis of prostatic cancer. We believe that f/tPSA is not a definitive test for diagnosing prostatic cancer. Our observations on the behavior of percent free PSA in relation to prostatic carcinoma grading and staging and in the follow-up of carcinoma patients are interesting; however, further studies are needed to define the appropriate role of f/tPSA in patients with an established diagnosis of prostatic carcinoma and in the follow-up of patients with prostatic cancer.     

Evaluation of prostate-specific antigen in untreated prostatic carcinoma

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of a prostate-specific antigen as a serum marker of prostatic cancer

Combined measurement of serum prostate-specific antigen (PA) and prostatic acid phosphatase (PAP) was performed in 235 patients with various urologic diseases including 55 patients with prostatic cancer. A PA level of over 24.7 ng/ml and a PAP level of over 3.1 ng/ml were considered to be positive. The positive rate of PA was 57% in the patients with untreated prostatic cancer and 3% in the patients without prostatic cancer. The positive rate of PAP was 52% in the patients with untreated prostatic cancer and 1% in the patients without prostatic cancer. PA and PAP were considered to be equally sensitive and specific serum markers of prostatic cancer. However, the positive rate increased to 65% without increasing the false positive rate when the PA and PAP were both measured simultaneously. The combined assay of PA and PAP is recommended for screening prostatic cancer. The cross-over titer of PA and gamma-Sm using standard samples in each kit revealed linearity, which suggested that PA and gamma-Sm possess the same antigenicity.     

The clinical use of the prostate-specific antigen in patients with prostatic cancer]

Radioimmunoassay determination of prostatic-specific antigen (PSA) was conducted in 71 patients with prostatic cancer varying in stages. 85 serum samples were investigated. Of 21 newly diagnosed cases PSA was elevated in 16 (76.2%). No significant elevation of the marker was noticed in stage II patients, while at stage III and IV PSA levels were universally increased. The mean PSA level for stage III was 149.5 ng/ml, for stage IV 291.4 ng/ml. Two stage II patients in remission out of ten presented with high PSA concentrations, while in partial remission this was observed in 3 cases out of 9.50% occurrence of PSA elevated level was registered for stage III patients in remission, 100% occurrence in progression. Prostatic cancer stage IV manifested high PSA levels in 33% of cases under stabilization and in 100% in progression.     

Multiple marker evaluation in prostatic cancer with prostatic acid phosphatase, γ-seminoprotein and prostate-specific antigen

Serum prostatic acid phosphatase (PAP), γ-seminoprotein (γ-Sm), and prostate-specific antigen (PA) levels were measured in 63 untreated patients with prostatic cancer. The sensitivities of PAP, γ-Sm, and PA as markers of malignancy were 68%, 83%, and 77%, respectively. The latter two markers were more sensitive than PAP, especially in stage B disease. The specificities of PAP, γ-Sm, and PA were 95%, 93%, and 93%, respectively. Patients with multiple positive markers were very likely to have prostatic cancer. In reactivation of the disease, positive rates for γ-Sm and PA were higher than for PAP, indicating that the former two markers are more reliable for monitoring prostatic cancer.     

Contribution of bone scintigraphy, prostatic acid phosphatase and prostate-specific antigen to the monitoring of prostatic cancer

Changes in the serial measurements of serum prostatic acid phosphatase (PAP), and prostatic specific antigen (PSA) have been compared against changes in serial bone scans in 120 patients with prostatic cancer. Of 54 patients who presented with negative bone scans 10 developed skeletal metastases, the PAP and PSA levels were rising in 5 and 9 of these patients, respectively. Local progression occurred in a further 9 patients in whom PAP was rising in 8 and PSA in all 9. In the 66 patients with previously documented skeletal metastases bone scan evidence of progression was seen in 36. At the time of the first evidence of progression PAP was rising in 20 (55%) and PSA was rising in 26 (72%). In 4 patients neither marker was raised at the time of first evidence of progression. We discuss the value of 'routine' serial bone scintigraphy in monitoring patients with prostatic cancer.     

Urethral metastasis from prostatic carcinoma as diagnosed by immunoperoxidase technique using prostate-specific antigen and prostate-specific acid phosphatase

A rare case of urethral metastasis from prostatic adenocarcinoma is reported. Ordinary histological examination by hematoxylin and eosin staining could not determine whether the primary site was the prostate or the urethra. However, with an immunoperoxidase technique using prostate-specific acid phosphatase and prostate-specific antigen as markers for prostatic cells, we obtained a precise diagnosis of the primary sites. As a result, the patient could be successfully treated with hormonal therapy.     

Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA.     

An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density

Summary Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1–10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important. The use of PSAD provides unique information regarding the need for biopsy and the likelihood of CaP. At PSA levels ranging between 10.1 and 20.0 ng/ml, PSAD will identify those patients who are less likely to have CaP, but all should undergo biopsy. If the PSA value is >20 ng/ml, all patients should undergo a biopsy.     

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.