Daily variability in human serum prostate-specific antigen and prostatic acid phosphatase: a comparative evaluation

The daily variation of serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) was investigated simultaneously in 10 patients with osseous metastatic prostatic cancer, 10 patients with benign prostatic hyperplasia, and 10 volunteers without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis (two-factor analysis of variance comparing time period to disease group) of the mean PSA and PAP levels at the four sampling times on all patient groups demonstrated no evidence of circadian rhythmic variation or any other distinct pattern for the observed sample times. Overall, the variability in PSA levels was significantly less than that observed for PAP. There was no significant difference in mean percent variation between patient groups (cancer, benign, and normal prostate glands) for both the PSA and PAP assays. Our data reveal that serum PSA measurements fluctuate unpredictably over the course of a day in patients with and without prostatic disease, but to a lesser extent than that seen for serum PAP values. These findings illustrate the potential inaccuracy of single determinations of serum PAP or PSA levels for monitoring disease recurrence and treatment response in patients with prostate cancer.     

Circadian variation of different fractions of serum acid phosphatase

The circadian variation of different fractions of serum acid phosphatase was determined in two men with a normal prostate, two men with benign prostatic hyperplasia, and four men with prostatic cancer. Serum samples were obtained every 2 hours from 8:00 a.m. until 6:00 a.m. the following day. An overall sample standard deviation of 1.98 U/liter was calculated for total acid phosphatase, 0.4 U/liter for tartrate-labile acid phosphatase, and 0.13 micrograms/liter for prostatic acid phosphatase as determined by immunoenzyme assay.     

Changes in serum acid and alkaline phosphatase and leucine aminopeptidase activities following massage of the prostate

The changes in serum alkaline phosphatase, total acid phosphatase, prostatic acid phosphatase and leucine aminopeptidase activities following massage of the prostate in patients with carcinoma or benign hyperplasia of the prostate having premassage control activities of a definite range were studied. Statistical significance of results was calculated by the F method. The results are as follows: 1) Following massage of the prostate the total serum acid phosphatase activity increased significantly, more markedly in benign hyperplasia than in carcinoma, and this may help to differentiate benign hyperplasia from carcinoma of the prostate. 2) Following massage of the prostate, serum alkaline phosphatase, prostatic acid phosphatase and leucine aminopeptidase activities showed no significant changes in either group.     

Lack of value of radioimmunoassay for prostatic acid phosphatase as a screening test for prostatic cancer in patients with obstructive prostatic hyperplasia

We examined the incidence of prostatic cancer in patients with an elevated radioimmunoassay for prostatic acid phosphatase and clinical benign prostatic hyperplasia on digital rectal examination. Of 295 patients screened with prostatic acid phosphatase tests 17 fulfilled the criteria of having an elevated prostatic acid phosphatase, clinically benign prostate and histological examination of the prostatectomy specimen. None of the 17 patients had histological evidence of prostatic cancer. The results confirm the predictions of mathematical models that prostatic acid phosphatase is of no practical value as a screening test for prostatic cancer in patients with clinical benign prostatic hyperplasia.     

The significance of prostatic acid phosphatase in adenocarcinoma of the prostate

Our radioimmunoassay for prostatic acid phosphatase was compared to commercial radioimmunoassay kits. A close correlation among all 3 assays was found in control groups, and in patients with benign prostatic hyperplasia and adenocarcinoma of the prostate. These results also were compared to recent reports from other centers using similar methodologies. In 7 to 15 per cent of the patients with bone metastasis normal levels of serum prostatic acid phosphatase were found. Variability in prostatic acid phosphatase production by the tumor may account for this finding. Elevated levels of prostatic acid phosphatase were associated more commonly with less differentiated primary tumors. A low percentage of prostatic acid phosphatase elevations in patients with early localized and incidental adenocarcinoma was found for the 3 assays evaluated. These factors, along with the falsely positive rates in patients with benign disease, limit severely the application of these assays to the screening of male patients at risk for adenocarcinoma of the prostate.     

Serum acid phosphatase elevation associated with transurethral resection syndromes

In 6 patients undergoing transurethral resection of the prostate for benign prostatic hyperplasia symptoms of post-transurethral prostate resection syndrome developed. Serum acid phosphatase determinations in the recovery room showed that all patients had high acid phosphatase levels although each had normal levels preoperatively. All patients showed a normal acid phosphatase level on the first postoperative day. The acid phosphatase elevations indicate significant intraoperative absorption of prostate tissue substances. The association of clinical symptoms with enzyme elevation suggests that the etiology of the confusing clinical syndromes following transurethral prostate surgery may be due to the intravenous absorption of not only irrigant solution but also tissue substances from the prostate gland.     

p53 antibodies in the serum of patients with prostate cancer

We assessed the potential clinical utility of levels of p53-specific antibodies as a novel serum biomarker of prostate cancer that could be used in conjunction with level of PSA. Material and methods Serum levels of p53-specific antibodies in patients with relapsed, newly diagnosed prostate cancer and in patients with benign prostate hyperplasia were quantified by an enzyme-linked immunoabsorbent assay. Result There was no significant difference (P = 0.96) between the serum levels of p53-specific antibodies in patients with newly diagnosed prostate cancer and with benign prostatic hyperplasia. In the newly diagnosed prostate cancer group, stage T1c (n = 8) showed the lowest p53-specific antibody level. However, the difference between T1c group and benign prostatic hyperplasia group was not significant (P = 0.686). The relapsed cancer group tended to have low levels of the antibodies, and, there was no significant difference between the relapsed prostate cancer group and the benign prostatic hyperplasia group (P = 0.14). The serum levels of p53-specific antibodies in patients with metastatic and with localized prostate cancer showed no significant difference (P = 0.68). Conclusion The use of titers of p53-specific antibodies to make differential diagnosis between prostate cancer and benign prostatic hyperplasia might have no role, and the antibodies should not be used as a marker of prostate cancer by itself. Because our study is based on small number of patients, further studies are necessary before its absolute validity can be determined.     

Radioimmunoassay of serum prostatic acid phosphatase after prostatic massage

The effect of prostatic massage on the concentration of prostatic acid phosphatase (PAP) in blood serum as determined by radioimmunoassay (RIA) was compared with that determined by a standard enzymatic assay (EA). Serum was drawn from 24 men before prostatic massage and after--at specified intervals, up to twenty-four hours. Three of these men were young, normal controls; 10 had biopsy-proved prostate cancer (CA); 11 had histologically confirmed benign prostatic hyperplasia (BPH). After prostatic massage, 3 of the 10 CA patients (30%) had elevation of PAP as determined by EA and 4 of the 11 BPH patients (36%) as determined by RIA. None of the controls showed elevated levels of PAP by either assay. In all patients elevated levels of PAP by both assays had returned to normal twenty-four hours after massage. It was concluded that serum for PAP testing by either assay method should be drawn before or twenty-four hours after rectal examination to prevent false positive results and the need for retesting.     

Clinical assessment of solid phase immunoadsorbent assay of human prostatic acid phosphatase

A new solid phase immunoenzyme assay for human prostatic acid phosphatase was tested in clinical practice. Clearly elevated levels of prostatic acid phosphatase (PAP) were found with advancing age and even more so in patients with benign prostatic hyperplasia (BPH). In patients with localized carcinoma of the prostate there was no elevation of levels above those observed in patients with BPH. When lymph node metastases were found at staging lymphadenectomy, the preoperative level of prostatic acid phosphatase was elevated in 7 of 12 cases. Good response to hormone treatment of metastatic carcinoma of the prostate was indicated by decrease of PAP-levels to normal. Rising levels often preceded the clinical manifestation of progression.     

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 102 men before hospitalization for radical prostatectomy. Prostate specimens were subjected to detailed histological and morphometric analysis. Levels of prostate specific antigen were significantly different between patients with and without a Gleason score of 7 or greater (p less than 0.001), capsular penetration greater than 1 cm. in linear extent (p less than 0.001), seminal vesicle invasion (p less than 0.001) and pelvic lymph node metastasis (p less than 0.005). Prostate specific antigen was strongly correlated with volume of prostate cancer (r equals 0.70). Bivariate and multivariate analyses indicate that cancer volume is the primary determinant of serum prostate specific antigen levels. Prostate specific antigen was elevated 3.5 ng. per ml. for every cc of cancer, a level at least 10 times that observed for benign prostatic hyperplasia. Prostate specific antigen is useful as a preoperative marker because no patient with lymph node metastasis had serum levels of less than 10 ng. per ml. (4 times the upper limit of normal range). Of the patients with greater than 50 ng. per ml. two-thirds had microscopic lymph node metastasis and 90 per cent had seminal vesicle invasion. Serum prostatic acid phosphatase levels showed a significantly weaker correlation with cancer volume (r equals 0.51) and every other pathological parameter. Of the patients 73 per cent had serum prostatic acid phosphatase levels in the normal range (0 to 2.1 ng. per ml.), including 7 per cent who had pelvic lymph node metastasis. Postoperative prostate specific antigen values were available in 97 of 102 patients, with a mean and maximum followup of 12 and 38 months. No patient with pelvic lymph node metastasis achieved an undetectable prostate specific antigen level without adjunctive therapy (hormonal or radiation). No difference in preoperative or postoperative prostate specific antigen levels, cancer volume, seminal vesicle invasion or incidence of pelvic lymph node metastasis was seen between patients with no capsular penetration and those with minimal capsular penetration (1 cm. or less total linear extent of full thickness penetration), providing the first quantitative evidence that small amounts of capsular penetration may not be of biological or prognostic significance.     

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.     

Serum acid phosphatase in patients with localised prostatic cancer, benign prostatic hyperplasia or normal prostates.

Serum acid phosphatase levels were determined in 247 men with surgically confirmed intracapsular prostatic cancer (30 patients), benign prostatic hyperplasia (BPH) (114 patients) or palpably normal prostates (103 men). Both radioimmunoassay (245 cases) and an enzymatic method (218 cases) were used. Using radioimmunoassay, the mean serum prostatic acid phosphatase (PAP) level was significantly higher in patients with BPH than in patients with intracapsular cancer or men with normal prostates. The weight of hyperplastic tissue removed during operation in the BPH group correlated closely with PAP concentrations. Age or the presence (or absence) of an indwelling catheter had no effect on PAP concentration. Using the enzymatic method, the highest levels of acid phosphatase were also detected in patients with BPH but the difference was less marked. It was concluded that intracapsular cancer does not elevate serum acid phosphatase levels as determined by radioimmunoassay or an enzymatic method. BPH alone leads to significant rises in PAP concentrations. The degree of BPH correlates with PAP levels.     

A preliminary study of JM-27: a serum marker that can specifically identify men with symptomatic benign prostatic hyperplasia

PURPOSE: Benign prostatic hyperplasia is a common disease in men that until recently was considered a single disease with varying symptoms. Our recent analysis has revealed that a molecular marker, JM-27, is able to distinguish at the tissue level between highly symptomatic individuals and those with histological disease. The goal of these studies was to determine if a serum based assay to detect JM-27 could distinguish men with different forms of benign prostatic hyperplasia. MATERIALS AND METHODS: A serum based enzyme-linked immunosorbent assay was developed using a novel anti-JM-27 monoclonal antibody. The assay was sensitive, detecting JM-27 at the low ng/ml level within the serum. A quantitative measurement of serum JM-27 levels was performed in 68 patients. The patients consisted of 3 groups of 29 patients with asymptomatic benign prostatic hyperplasia (American Urological Association symptom score of 15 or less), 39 with symptomatic benign prostatic hyperplasia (American Urological Association symptom score 16 to 32) and 17 with confirmed prostate cancer. The assay cutoff was determined after a pilot run of samples and applied prospectively. RESULTS: Using the determined cutoff, serum levels of JM-27 can distinguish between symptomatic and asymptomatic patient sets. The sensitivity and specificity of the assay are 90% and 77%, respectively. The presence of prostate cancer in these men does not appear to alter the marker levels. CONCLUSIONS: The present study is believed to represent the first characterization of a serum based marker for severe benign prostatic hyperplasia.     

Elevation of serum prostatic acid phosphatase levels after prostatic massage

The effect of prostatic massage on the serum prostatic acid phosphatase (PAP) levels determined by radioimmunoassay (RIA) was studied in 29 patients with benign prostatic hyperplasia (BPH) and 7 patients with prostatic carcinoma (CA). Among the BPH patients, 77 per cent (P less than 0.001) showed an increase in post-massage PAP levels but only 3 (10%) showed an increase to more normal levels.     

Characterization of secretion pattern of human prostatic acid phosphatase: a reassessment

The daily variation of serum levels of prostatic acid phosphatase (PAP) determined by the Roy enzymatic method was investigated in 10 patients with metastatic prostatic cancer and in 10 patients without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis of the mean PAP levels at the four sampling times in both groups of patients demonstrated no evidence of circadian or diurnal rhythmic variation. Prostate cancer patients did show significantly greater variability in daily PAP than patients without prostatic disease, although a distinct pattern of secretion was not observed in either group. These results underscore the potential inaccuracy of the use of single determination of serum PAP as a parameter of response in patients with metastatic prostatic cancer and in the staging of patients with clinically localized prostatic malignancy. Evaluation of trends of PAP levels over time, however, continues to play a major role in the assessment and management of patients with prostatic carcinoma.     

Comparison of prostate secretory protein with prostate specific antigen and prostatic acid phosphatase as a serum biomarker for diagnosis and monitoring patients with prostate carcinoma

Serum prostate secretory protein (PSP) levels were measured in 49 patients with benign prostatic hyperplasia (BPH), 144 patients with various stages of prostatic carcinoma (CaP), and 82 CaP patients who were followed serially. PSP values were compared with serum levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). In the BPH group, PSP was elevated (> 10 ng/ml) in 41% of patients, whereas PSA (> 4 ng/ml) and PAP (> 3.3 ng/ml) were elevated in 39% and 23% of the cases, respectively. PSP levels were elevated in 48% of the CaP pretreatment specimens, compared to 79% for PSA and 40% for PAP. PSP levels in cancer patients who had intracapsular disease were about two to three times higher than those observed for PAP. PSP was found to be the only marker elevated in eight (6%) pretreatment CaP patient serum specimens, while PAP was never found to be elevated when PSA was normal. PSP serum concentrations correlated with the clinical course of the disease in 79% of patients, compared with 90% for PSA and 66% for PAP. In certain patients, monitored over time, disease correlation was reflected in serum values with only a single biomarker, i.e., 1% with PAP, 8% with PSP, and 10% with PSA. This study has shown that PSP is a less sensitive serum biomarker than PSA, but more sensitive than PAP for detection and monitoring the early stages of prostate cancer. This suggests that PSP as a biomarker may be a useful adjunct for the management of a subpopulation of low-stage and -grade CaP. © 1993 Wilcy-Liss, Inc.     

Serum YKL-40 levels and chitotriosidase activity as potential biomarkers in primary prostate cancer and benign prostatic hyperplasia

BACKGROUND: YKL-40, also called human cartilage glycoprotein-39 (HC gp-39) and chitotriosidase are homologs of family 18 glycosyl hydrolases secreted by human macrophages. Although high levels of YKL-40 and chitotriosidase are associated with several diseases, the physiological functions of these enzymes are still unclear. YKL-40, a growth factor for connective tissue cells, a migration factor for endothelial and vascular smooth muscle cells, is expressed by several types of solid human carcinoma, including prostate carcinoma. PURPOSE: The purpose of this study was to compare serum YKL-40 levels and chitotriosidase activity both in benign prostatic hyperplasia and primary prostate cancer. METHODS: YKL-40 and chitotriosidase were determined in serum samples from 93 patients with primary prostate cancer and 61 patients with benign prostatic hyperplasia. Serum YKL-40 levels were measured by ELISA and chitotriosidase activity was determined by fluorometer. PSA levels were also measured by using an automated system. RESULTS: Serum YKL-40 levels were significantly higher (P < 0.001) in patients with prostate cancer compared with control group whereas there was no significant difference between BPH and control group. Serum chitotriosidase activities were significantly higher in carcinoma patients with high Gleason score than the control group (P < 0.001). No significant difference was observed in BPH patients (P > 0.05). Both YKL-40 and chitotriosidase were found statistically significant higher in primary prostate cancer and BPH. CONCLUSION: High serum YKL-40 levels in patients with primary prostate cancer indicate that YKL-40 may have a function in the progression of malignant diseases, whereas no significant elevation was observed in benign prostatic hyperplasia. Meanwhile, high serum chitotriosidase activity was observed only in patients with Gleason high grade, indicating possible macrophage involvement in cancer progression. Further studies are needed to elucidate the biologic role of YKL-40 in cancer aggressiveness and in progression of malignant diseases.     

Differential response of prostate specific antigen to testosterone surge after luteinizing hormone-releasing hormone analogue in prostate cancer and benign prostatic hyperplasia

OBJECTIVE: To investigate any differences in changes in serum prostate specific antigen (PSA) levels in patients with benign and malignant prostatic disease in response to the testosterone surge after administering a luteinizing hormone-releasing hormone (LHRH) analogue. PATIENTS AND METHODS: The study included 54 patients referred to the urology clinic with intermediate PSA levels (4-10 ng/mL) or an abnormal digital rectal examination. Forty-five patients received a single injection of LHRH analogue depot each at one week before prostate biopsy and nine served as a control group. Changes in PSA levels in response to the testosterone surge from the LHRH analogue were recorded after 5 and 7 days, and were correlated with the biopsy results. The PSA changes were compared with basal PSA levels and the free/total PSA ratio(f/tPSA). RESULTS: Of the 45 patients who underwent prostate biopsy, histopathology showed prostate cancer in 11, benign prostatic hyperplasia in 33 and prostatic intraepithelial neoplasia in one. Patients with cancer had a significantly greater increase in serum PSA levels during the first week after LHRH injection than those in the benign and control groups. Receiver operating characteristic curves showed that the percentage change in PSA level on day 5 was more diagnostic than total PSA and f/tPSA. CONCLUSIONS: There was a marked difference in the PSA response of patients with benign or malignant disease to the testosterone surge produced by the LHRH analogue. Although a larger study would be needed before LHRH-induced provocation could be proposed as a clinical test, in this small series the response was better than that for total PSA or f/tPSA in differentiating benign and malignant disease.     

前列腺癌组织中ErbB-3和LAT-1表达的研究

目的:分析表皮生长因子受体家族中的ErbB-3受体和氨基酸转运蛋白L型氨基酸转运体-1(LAT-1)在临床前列腺癌组织标本中的表达和定位,以及二者之间可能存在的相关性。方法:对45例前列腺癌组织标本,10例良性前列腺增生组织(BPH)标本和9例正常前列腺标本的石蜡切片采用免疫组织化学SABC方法染色并进行分析。结果:在45例前列腺癌组织中有33例(73.3%)细胞质或细胞核呈现ErbB-3染色阳性;10例BPH标本中,仅有1例出现阳性反应(P<0.001);正常前列腺组织中未见到阳性表达(P<0.001)。而LAT-1在前列腺癌组织中的表达阳性率高于ErbB-3,为40例(88.9%),表达于细胞膜和或细胞质中,明显高于正常组织以及BPH组织(P<0.05)。LAT-1在正常组织和BPH组织中无阳性表达。ErbB-3和LAT-1在前列腺癌组织中的表达均与Glean评分分级无关。在前列腺癌组织中ErbB-3和LAT-1的表达存在正相关性(r=0.426,P<0.05)。结论:在前列腺组织中的ErbB-3和LAT-1阳性表达和定位能够区分恶性肿瘤与BPH和正常前列腺组织,有利于前列腺癌的诊断和生物学的预测。