Clinical studies of gamma-seminoprotein in prostatic disease. I. Clinical evaluation of serum gamma-seminoprotein

Serum gamma-seminoprotein (gamma-Sm) in patients with prostatic disease was determined by enzyme immunoassay. A total of 136 patients including 13 untreated and 40 treated patients with prostatic cancer, 45 patients with benign prostatic hyperplasia (BPH) and 38 patients with other urological diseases were analyzed. The mean +/- SD of serum gamma-Sm in the 13 patients with untreated prostatic cancer and the 45 patients with BPH was 31.7 +/- 46.1 and 3.7 +/- 6.6 ng/ml, respectively, there being a statistically significant difference between the two groups. All patients with untreated stage A or B prostatic cancer had a serum gamma-Sm of less than 4 ng/ml (cut off value). The mean level of serum gamma-Sm was 5.1 +/- 1.9 ng/ml for all patients with untreated stage C prostatic cancer; 66% of them had a value above the cut off value. However, it was 55.9 +/- 52.6 ng/ml in all patients with untreated stage D prostatic cancer; 87.5% of them had a value above the cut-off value. These results suggest that gamma-Sm may be a useful tumor marker in the management of patients with prostatic cancer.     

Clinical evaluation of serum prostatic specific antigen in prostatic cancer: simultaneous assays of prostatic specific antigen, gamma-seminoprotein and prostatic acid phosphatase in 113 newly diagnosed patients with prostatic cancer

Serum prostatic specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) levels were measured in 113 untreated patients with prostatic cancer and in 137 patients with benign prostatic hypertrophy (BPH). We used a PA-TESTWAKO enzyme immunoassay kit, gamma-Sm enzyme immunoassay kit and PAP radioimmunoassay kit. Of the 113 patients, 81.4%, 73.5% and 69%, respectively, were detectable using a single assay. PA was more sensitive than the other two markers in all stages, especially in localized disease (stages A, B and C). Using the BPH group as a negative control, specificities of PA, gamma-Sm and PAP were 85.4%, 81.0% and 94.2%, respectively. Efficiency was, respectively, 81.2%, 79.6% and 82.8%. In the follow up period, 15 patients presented disease progression. At the time of clinical detectable progression, the sensitivities of PA and gamma-Sm were both 100% (15/15), while 67% (10/15) for PAP. Concerning the sensitivity within 6 months prior to progression, gamma-Sm and PA tended to be more sensitive than PAP in early detection of disease progression. This study shows that PA is more reliable than gamma-Sm and PAP in detecting and staging of prostatic cancer. gamma-Sm and PA appear to be more reliable in earlier prediction of disease progression.     

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 evaluation of gamma-seminoprotein in prostate cancer

Gamma-seminoprotein (gamma-Sm), a potential new marker for prostate cancer, has been evaluated with a sandwich-type enzyme immunoassay (EIA). This assay system has been confirmed to have a sensitivity and detectable range of 3.0 and 3.0-100 ng/ml, respectively, with a high reproducibility (approximately equal to 6% coefficient of variation between assays). A total of 256 serum samples were drawn from normal Japanese subjects for detection of gamma-Sm. Serum gamma-Sm was undetectable (less than 3.0 ng/ml) in 26 samples from 26 females. In 230 male cases, serum gamma-Sm levels ranged from less than 3.0 to 4.0 ng/ml. These values were not related to age. An upper normal limit of 3.6 ng/ml was calculated for 99 percentile Japanese males (n = 103) over 50 years of age. Serum gamma-Sm was detected in 192 untreated male patients with urological diseases. Gamma Sm levels (mean +/- SD) in each disease were as follows: prostate cancer (n = 64) 11.0 +/- 17.9 ng/ml; benign prostatic hypertrophy (n = 50), 3.02 +/- 0.113; bladder cancer (n = 58), 3.13 +/- 0.514; and renal adenocarcinoma (n = 30), 3.26 +/- 1.01. Serum gamma-Sm levels were statistically higher (p less than 0.05) in the prostate cancer group, however, there was no statistical difference in gamma-Sm levels among clinical stages or histopathologic grades. Furthermore, serum gamma-Sm values showed no correlation (r = 0.3870) with prostatic acid phosphatase (PAP), but were slightly correlated to prostate antigen (PA) levels (r = 0.6980) in patients with prostate cancer. These results suggest that gamma-Sm is a potential tumor marker of prostate cancer and that serially detected serum gamma-Sm levels could be used to monitor the disease.     

Multiple marker evaluation in prostatic cancer using prostatic specific antigen, gamma-seminoprotein and prostatic acid phosphatase

Serum prostatic specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) were evaluated in 141 patients with prostatic cancer, 121 of whom were newly diagnosed. Of the 121 untreated patients, 77, 71 and 67% were detectable by the PA, gamma-Sm and PAP markers, respectively. PA was equally or more sensitive in all stages than the other two markers. Using the benign prostatic hypertrophy group (131 patients) as a negative control, the specificities of PA, gamma-Sm and PAP were 89, 76 and 83%, respectively. Combination of PA, gamma-Sm and PAP increased sensitivity to 86%, especially in localized disease (stages A, B and C) to 74%, but did not improve specificity (67%) or efficiency (76%). During the follow-up period of 1-53 months, 24 of 141 patients with prostatic cancer had disease progression. All serial levels of gamma-Sm, PA, and PAP were positive in 17, 12 and 10 of the 24 patients within 6 months prior to detectable disease progression. gamma-Sm appeared to be more sensitive than the other two markers for early detection of disease progression. These results suggest that PA and gamma-Sm are reliable markers for detection and monitoring of prostatic cancer.     

Serum gamma-seminoprotein determination in prostatic cancer.

Serum gamma-seminoprotein (gamma-Sm) was evaluated as a new marker for prostatic cancer in comparison with prostatic acid phosphatase (PAP). The sensitivity of gamma-Sm and PAP for untreated prostatic cancer was 81% and 67%, respectively. gamma-Sm showed a higher positive rate over all stages than in benign prostatic hypertrophy (BPH). There was no correlation between gamma-Sm and PAP in prostatic cancer. Improved sensitivity was obtained by simultaneous measurement of gamma-Sm and PAP. Specificity of gamma-Sm and PAP for BPH was 87% and 90%, respectively. gamma-Sm normalized after endocrine therapy for stage D2 more often than did PAP. These results indicate that gamma-Sm is another useful marker to evaluate prostatic cancer.     

Clinical studies of gamma-seminoprotein in prostatic disease. II. Immunohistochemical study of gamma-seminoprotein

Localization of gamma-seminoprotein (gamma-Sm) was examined using horseradish peroxidase-labeled anti-gamma-Sm antibody (Chugai Corp. Ltd., Tokyo, Japan) by the enzyme-labeled antibody method in paraffin embedded specimens of 18 benign prostatic hyperplasias and 32 untreated prostatic cancers. The level of serum gamma-Sm was also determined by enzyme immunoassay in 10 untreated patients with prostatic cancer and 18 with benign prostatic hyperplasia. Specific gamma-Sm staining was detected in prostatic glandular epithelial cells and prostatic secretion of all specimens of benign prostatic hyperplasias and a half of the specimens of prostatic cancers. Specific gamma-Sm staining was shown to correlate with histological differentiation of the prostatic cancer, but no correlation was found between specific gamma-Sm staining and the level of serum gamma-Sm.     

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.     

Serum prostatic acid phosphatase, gamma-seminoprotein and prostatic specific antigen in hemodialysis patients.

Serum concentrations of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PSA) were measured in 31 hemodialysis patients without clinical signs of malignant disease. PAP, gamma-Sm and PSA levels in serum were not significantly different between control and hemodialysis groups. A significant reduction in these tumor markers was not found after dialysis treatment. This indicates that the measurement of PAP, gamma-Sm and PSA in serum is useful for the detection of prostatic cancer in patients undergoing hemodialysis.     

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.     

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.     

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.     

Clinical study on prostatic cancer patients

Clinical observations on prostatic cancer were studied in 27 patients who had been managed in our department between April, 1980 and December, 1986. The mean age at the time of initial clinical visit was 70.6 years old with a range of 55 to 88 years old. Of all 27 patients, 15 men (55.6%) were senior citizens over 70 years old and indeed 23 men (85.2%) were over 60 years old. According to the general rules for clinical and pathological studies on prostatic cancer, there were 10 patients with stage A, 2 patients with stage B, and 15 patients with stage D disease. However, none of our patients had stage C foci of prostatic cancer. Histopathologically, biopsied or surgically resected specimen all showed adenocarcinoma. More frequently the incidence of poorly differentiated adenocarcinoma was found in the specimen from the patients with advanced clinical disease. Anti-androgen therapy with castration or a combined hormonal manipulation initially was done in 25 patients. Simple hormonal treatment using chlormadinone acetate (CMA) was given in 13 patients. Of 25 patients who received hormone treatment, 22 underwent castration whereas, 12 of 13 having undergone single hormonal therapy were castrated. Combined chemohormonal therapy using UFT and CMA or additionally given estramustine phosphate disodium (Estracyt) was subjected only to stage D disease of prostatic cancer. Of 15 patients surgically treated, 11 received transurethral resection of the prostate on the basis of initial diagnosis of benign prostate hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation on serum osteocalcin in advanced prostate cancer patients]

The clinical significance of osteocalcin as a marker for advanced prostate cancer was examined. Osteocalcin is produced by osteoblasts and is also detected in the blood. Its change is a good index of osteometabolic diseases and especially of the osteoblastic activity. In the present study, we examined the serum osteocalcin concentration of those patients with urogenital tumor, especially prostate cancer, who had been confirmed for multiple bone-metastasis by clinical examination. These patients comprised an untreated group (15 cases) of patients with prostate cancer presenting confirmed bone-metastasis, and a group of patients without bone-metastasis. The respective serum osteocalcin concentrations of these two groups were compared with 51 cases of prostate hypertrophy used as the control group. The findings revealed that the serum osteocalcin concentration demonstrated high values in the first group with a tendency toward lowering during treatment. Neither the latter group nor the control group showed high values. On the other hand, false-positive cases (8%), and false-negative cases (20%) were found. In the case of bone-metastasis, these results suggest that measurement of serum osteocalcin concentration is useful for clinical periodical observation about the activity of the bone metastatic focus.     

Clinical significance of tumor markers in prostatic carcinoma--comparative study of prostatic acid phosphatase, prostate specific antigen and gamma-seminoprotein

We measured the prostatic acid phosphatase (PAP), gamma-Seminoprotein (gamma-Sm) and prostate specific antigen (PA) in the serum of 862 patients with various urologic diseases including 89 patients with prostatic cancer. We used a PAP radioimmunoassay kit, gamma-Sm enzyme immunoassay kit, Markit-F-PA enzyme immunoassay kit and PA test Wako enzyme immunoassay kit. Serum PA level in advanced prostatic carcinoma (stage C, D) tended to be higher than that in early stage cancer (stage A, B). The Wako kit gave a higher PA than the Markit-F in each stage. The sensitivity rate of Wako PA test was the highest (81%) of all kits. The specificity rate of PAP was the highest (83%), and the accuracy rate of Markit-F PA was the highest (79%). The positive rate in the combined assay of PAP, gamma-Sm and PA in prostatic cancer was higher than that in the single assay of each tumor marker. We regarded PAP, gamma-Sm and PA as clinically different tumor markers, because their serum level did not correlate definitely. No apparent correlation was found between histopathological grade and the level of each tumor marker. The level of PAP, gamma-Sm and PA in the reactivated patients was significantly higher than that of the well-controlled patients. In the reactivated patients, the positive rate of Markit-F PA was the highest (89%) of all the kits.     

Clinical evaluation of CMA in the treatment of prostatic cancer

Forty five patients with previously untreated prostatic cancer were given chlormadinone acetate (CMA) at a dose of 100 mg/day (mean 12.6 months), and 42 of them were evaluated for effectiveness. Overall response evaluation revealed 19 complete responses (45.2%), 14 partial responses (33.3%), 4 minor responses (9.5%), and 5 were unresponsive (11.9%). Consequently CMA was judged to be effective in 33 patients (78.6%, complete and partial responses). Response rate was 100.0% for stage A, 88.9% for stage B, 77.8% for stage C, and 57.1% for stage D. The response rate for stage D was relatively high, possibly because the time of judgement of effectiveness was a little too early. As side effects, elevated triglyceride level, impaired liver function and impotence were noted in one patient each. All of them were slight. The testosterone level in both castrated and non-castrated patients were not higher than that in women, and no significant difference in the level was noted between the groups. Nevertheless, the clinical usefulness of castration is not denied. CMA is considered useful as an endocrine therapeutic drug, though its effect on the disease at stage D was insufficient. The administration method, such as sequential treatment and combination treatment of CMA and estrogen preparations, is a future subject.