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 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.     

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. 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.     

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

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

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.     

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.     

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 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.     

前列腺癌内分泌治疗对血PSA的影响及其临床意义

目的探讨进展期前列腺癌（PCa）患者内分泌治疗前后前列腺特异性抗原（PSA）变化的临床意义。方法测定PCa患者内分泌治疗前和治疗后3、6、12、24个月血清PSA。结果治疗后3个月与治疗前相比血清PSA下降明显。治疗后6个月达到PSA谷值。结论血清PSA可作为判断PCa内分泌治疗效果的标准，血清PSA再次升高（〉4ng／ml）提示肿瘤发展为非激素依赖性前列腺癌，是预测生存率的一个独立因素。     

前列腺癌患者血清胰岛素样生长因子-1检测的临床意义

目的　探讨血清胰岛素样生长因子 1(IGF Ⅰ )与前列腺癌 (PCa)发生发展的关系。　方法　采用免疫放射分析法 (IRMA)检测 3 7例PCa、3 5例良性前列腺增生 (BPH)患者和 2 0例健康人血清IGF Ⅰ ,比较各期PCa血清IGF Ⅰ水平 ,并对 8例行根治性前列腺全切术后患者手术前后IGF Ⅰ水平随访。　结果　PCa组血清IGF Ⅰ ( 3 2 5 .6± 10 0 .8)ng/ml,明显高于BPH组 ( 2 0 1.6± 5 3 .8)ng/ml和健康组 ( 179.0± 5 7.2 )ng/ml,差异有显著性意义 (P <0 .0 1) ;BPH组与健康组比较差异无显著性意义 (P >0 .0 5 ) ;8例PCa患者术前IGF I( 3 15 .8± 87.0 )ng/ml,术后 ( 2 2 4.8± 88.4)ng/ml,差异有显著性意义 (P <0 .0 5 ) ;PCa患者各期血清IGF Ⅰ比较差异无显著性意义 (P >0 .0 5 )。　结论　IGF Ⅰ有可能作为临床上一个新的PCa检测指标预测高危人群 ,进行早期诊断     

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.     

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.     

gamma-Seminoprotein in serum of prostatic cancer

From August, 1981 to May, 1984, we measured gamma-seminoprotein in the serum of 51 untreated patients with prostatic cancer in the Chiba University Hospital. Prostatic acid phosphatase (radioimmunoassay) in serum was also measured in these patients. We also measured gamma-seminoprotein and prostatic acid phosphatase in serum of patients under control by hormonal treatment and of reactivated patients. In untreated stage B and stage C cases, positive rate of gamma-seminoprotein in serum was larger than that of prostatic acid phosphatase. Therefore the measurement of gamma-seminoprotein in serum is considered to be useful in the diagnosis of early prostatic cancer. Four weeks after hormonal treatment, gamma-seminoprotein in the serum of 74% of the patients returned to the normal level. The positive rate of gamma-seminoprotein in the serum of reactivated patients is significantly larger than that of the patients under control by hormonal therapy.     

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.     

前列腺癌组织中微血管密度测定及其意义

应用ＡＢＣ免疫组织化学技术对３９例前列腺癌和１０例前列腺增生症组织中微血管密度进行检测，结果发现前列腺癌组织中微血管密度明显高于ＢＰＨ；高分化前列腺癌组织中微血管密度明显低于低分化和未分化前列腺癌；发生转移的前列腺癌中微血管密度明显于未转移的前列腺癌。     

The prognostic significance of post-irradiation biopsy results in patients with prostatic cancer

To evaluate the prognostic significance of post-irradiation biopsy results in patients with prostatic cancer, we reviewed the records of 803 patients who had been treated with pelvic lymph node dissection, radioactive gold seed implantation and external beam irradiation. Of the patients 124 had 1 or more biopsies within 6 to 36 months after completion of radiotherapy when there was no evidence of local or distant recurrence of tumor. Patients were followed for a mean of 64 months (range 14 to 175 months) and received no other therapy before relapse. Over-all, 43 of these patients (35 per cent) had a positive biopsy result. The incidence of positive biopsy results correlated directly with the initial stage of the tumor, ranging from 22 per cent of stage B1N to 50 per cent of stage C1 lesions. However, biopsy results did not correlate with the grade of the tumor. Local recurrence and distant metastases were much more common among patients with a positive biopsy result (p equals 0.0006). Local recurrence developed in 58 per cent of the patients with a positive biopsy by 5 years and in 82 per cent by 10 years. Of those in whom all biopsies were negative only 18 per cent had local recurrence by 5 years and 32 per cent by 10 years. Biopsy results retained their prognostic significance even among the more favorable subset of patients whose pelvic lymph nodes were negative initially and those with a normal prostatic examination at biopsy. These results indicate that a post-irradiation prostate biopsy 6 to 36 months after completion of treatment can be used to determine the efficacy of a particular radiotherapeutic regimen as well as the success or failure of radiotherapy in an individual patient.