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Inflammation in prostate biopsies of men without prostatic malignancy or clinical prostatitis: correlation with total serum PSA and PSA density.

OBJECTIVE: Inflammation is a frequent histological finding in prostate biopsies, performed on men without prostatic malignancy or clinical prostatitis. We investigated the relationship between morphological parameters of inflammation in prostatic tissue and total serum prostate-specific antigen (PSA) and prostate-specific antigen density (PSAD) levels to determine if subclinical inflammation can cause elevation of PSA and PSAD. METHODS: We reviewed 268 prostate biopsies, performed on 238 men with elevated PSA and/or abnormal digital rectal examination of the prostate. All premalignant and malignant biopsies and cases of clinical prostatitis were excluded. The inflammation in the remaining 145 prostate biopsies was scored for extent of inflammation and aggressiveness of inflammation, using the four-point scale designed by Irani and co-workers. In this prostatic inflammation scoring system, extent of inflammation is graded from 0 up to 3 according to the degree of invasion of inflammatory cells in prostatic tissue. Aggressiveness of inflammation is graded from 0 up to 3 according to the degree of contact or disruption of prostatic glandular epithelium by inflammatory cells. RESULTS: Each of the studied biopsies showed inflammatory cells. Median PSA levels in grades 1, 2 and 3 of extent of inflammation were, respectively, 5.7, 6.8 and 13. 0. Median PSAD levels in these groups were 0.13, 0.16 and 0.33. There was no significant difference between these grades for PSA nor for PSAD. Median PSA levels in grades 0, 1 and 2 of aggressiveness of inflammation were, respectively, 3.9, 5.9 and 8.9. Median PSAD levels in these groups were 0.12, 0.18 and 0.17. For both parameters, there was a significant difference between grades (respectively, p = 0.0028 and p = 0.0330). CONCLUSION: Inflammation of the prostate is a histological finding in almost every set of prostate biopsies, even when there are no signs of clinical prostatitis. This subclinical inflammation can cause PSA elevation. Not the extent of inflammation is of importance, but the disruption of epithelial integrity caused by the inflammatory infiltrate. When confronted with a patient with an elevated PSA level whose prostate biopsies reveal no malignancy but only inflammation, this concept can help in determining the need for quick repeat biopsies.

Acute Disease↗

Immunohistochemical expression of retinoblastoma and p53 tumor suppressor genes in prostatic intraepithelial neoplasia: comparison with prostatic adenocarcinoma and benign prostate.

Mutational alterations involving the p53 and retinoblastoma (RB) tumor suppressor genes are implicated in the oncogenesis of a variety of tumors. Their role in the pathogenesis of prostatic adenocarcinoma remains to be fully elucidated, and their detection in high-grade prostatic intraepithelial neoplasia (HG-PIN) has not been closely examined. We studied the immunohistochemical expression of RB and p53 proteins in HG-PIN, benign prostate, and prostatic adenocarcinoma from 25 radical prostatectomy specimens. Formalin-fixed, paraffin-embedded tissue sections pretreated with antigen retrieval in citrate buffer were stained with anti-RB antibody RB-WL-1 and anti-p53 antibody DO-7. RB immunoreactivity was present in all of the cases in the foci of HG-PIN, benign prostate, and prostatic adenocarcinoma. Mutant p53 protein was detected in 56% of HG-PIN, 72% of prostatic adenocarcinomas, and 20% of benign prostatic glands. A multivariate analysis of variance showed an overall difference in p53 immunoreactivity between HG-PIN, benign prostate, and prostatic adenocarcinoma (P < .001). There was a statistically significant difference between immunoreactivity of the benign prostate and of HG-PIN (P < .001) and between the immunoreactivity of benign prostate and prostatic adenocarcinoma (P < .001). The immunoreactivities of HG-PIN and prostatic adenocarcinoma were not statistically different (P = .3). These data suggest that RB loss might not play a role in initiation of all cases of prostatic adenocarcinoma. The p53 immunoreactivity in HG-PIN was significantly different from that found in benign prostate and was similar to that of prostatic adenocarcinoma. This is in keeping with the putative premalignant character of HG-PIN.

Adenocarcinoma↗

A novel intraurethral prostatic bridge catheter for prevention of temporary prostatic obstruction following high energy transurethral microwave thermotherapy in patients with benign prostatic hyperplasia.

PURPOSE: We evaluate the efficacy and safety of a novel intraurethral prostatic bridge catheter in preventing temporary prostatic obstruction following targeted high energy transurethral microwave thermotherapy in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 54 patients with benign prostatic hyperplasia underwent high energy transurethral microwave therapy under topical urethral anesthesia followed by placement of a prostatic bridge catheter, which remained indwelling as long as 1 month (prostatic bridge catheter group). Patient evaluation included determination of peak urinary flow rate, International Prostate Symptom Score (I-PSS) and quality of life score at baseline, immediately following transurethral microwave therapy and prostatic bridge catheter placement, and periodically thereafter for 1 month. Results were retrospectively compared with those of 51 patients who underwent transurethral microwave therapy followed by standard temporary urinary catheterization, typically for 24 hours (standard catheterization group). RESULTS: Immediately following transurethral microwave therapy and prostatic bridge catheter placement significant improvements (p <0.0005) were observed in mean peak flow rate, I-PSS and quality of life score of 59.3, 33.5 and 23.6%, respectively, compared with baseline values. Further improvements were noted up to 1 month, at which time mean peak flow rate, I-PSS and quality of life score had improved 79.0, 54.9 and 56.5%, respectively, versus baseline (p <0.0005). In a retrospective comparison at baseline and 14 days between the prostatic bridge catheter group and standard catheterization group mean baseline peak flow rate, I-PSS and quality of life score were similar. However, at the 14-day followup evaluation in the prostatic bridge catheter group mean peak flow rate was 101.8% higher, and I-PSS and quality of life score were 47.9 and 51.1% lower, respectively, than the corresponding values in the standard catheterization group (p <0.0005). The prostatic bridge catheter was well tolerated and remained indwelling throughout the entire 1-month followup in 48 of 54 patients (88.9%). Early prostatic bridge catheter removal was required in 3 patients (5.6%) due to urinary retention and in 3 (5.6%) due to catheter migration. CONCLUSIONS: Prostatic bridge catheter placement provides an effective and well tolerated option for preventing prostatic obstruction in the acute period after transurethral microwave therapy. This approach avoids the inconvenience and infection risk of standard indwelling catheters or intermittent self-catheterization. Prostatic bridge catheter insertion and removal are rapid, facile, nontraumatic procedures. Prostatic bridge catheter may potentially be used in an array of minimally invasive procedures involving thermal treatment of the prostate gland.

Diathermy↗

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.

Adult↗

Serum-to-urinary prostate-specific antigen ratio: a potential means of distinguishing benign prostatic hyperplasia from prostate cancer.

OBJECTIVE: High concentrations of serum prostate-specific antigen (PSA) may be associated with the presence of benign prostatic hyperplasia or prostatitis. We investigated the serum-to-urinary PSA ratio in patients with or without prostate cancer to assess its efficacy in enhancing serum PSA specificity. METHODS: Patients presenting abnormal findings in digital rectal examination or documented prostate carcinoma were prospectively included in the study. A control group, with no evidence of prostate disease, hospitalized in the same time interval was included. Serum and urine PSA levels were measured in our laboratory with the Tandem R assay (Hybritech). Samples were drawn twice at 2-month intervals (M1 and M3). RESULTS: Sixty-eight patients were included in the study divided into 27 cases of benign prostatic hyperplasia, 20 of prostate carcinoma, 10 of prostatitis and 11 patients in the control group. Serum and urine PSA levels were not correlated (r < or = 0.1). There was no significant difference in any group from M1 to M3 as regards urinary PSA (p > or = 0.15). Intergroup comparison showed significantly (p < or = 0.004) high urinary PSA (mean level +/- SEM 28.3 +/- 3.4 micrograms/mmol creatinine) only in the benign prostatic hyperplasia group, mean levels in the prostate carcinoma, prostatitis and control groups being 3.7 +/- 1.1, 11 +/- 2.9 and 5.2 +/- 0.9 micrograms/mmol creatinine, respectively. Differences in urinary PSA levels between the confined prostate carcinoma and benign prostatic hyperplasia groups (p = 0.0008) were further increased when considering the serum-to-urinary PSA ratio (p = 0.0003). CONCLUSION: Our results suggest that the serum-to-urinary PSA ratio may be useful in distinguishing benign prostatic hyperplasia from prostate cancer.

Aged↗

Predictive value of total and percent free prostate specific antigen in high grade prostatic intraepithelial neoplasia lesions: results of the Tyrol Prostate Specific Antigen Screening Project.

PURPOSE: We evaluate the predictive values of total and percent free prostate specific antigen (PSA) in regard to high grade intraepithelial lesions in volunteers who participated in the Tyrol PSA Screening Project. MATERIALS AND METHODS: Between June 1995 and December 1998, 1,474 patients undergoing transrectal biopsy of the prostate were evaluated. The primary detection rates of prostate cancer and high grade intraepithelial lesions were evaluated. In addition, the rate of prostate cancer detected on biopsy in patients diagnosed with high grade prostatic intraepithelial neoplasia on the previous biopsy was assessed. Mean total PSA values and mean percent free PSA levels were determined for each study group and compared using the Mann-Whitney U test. RESULTS: A total of 1,077 (73.1%) volunteers had benign prostatic hyperplasia or prostatitis, and 327 (22.2%) had prostate cancer. The primary detection rate for high grade intraepithelial lesions was 4.7% (70 patients) and on repeat biopsy was 38.6% (27). Mean total PSA for the benign prostatic hyperplasia, prostate cancer, high grade and intraepithelial cancer groups were 6.0, 8.7, 5.9 and 5.2 ng./ml., respectively. Mean percent free PSA values for the various groups were 21.9, 12.1, 15.0 and 12.0, respectively. In regard to total PSA there was a statistically significant difference between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.016), as well as the prostate cancer and intraepithelial cancer groups (p = 0.028). However, the high grade and intraepithelial cancer groups did not differ significantly. In regard to percent free PSA there were statistically significant differences between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.0001), and the high grade and intraepithelial cancer groups (p = 0.013). CONCLUSIONS: In regard to percent free PSA our data indicate a significant difference between high grade intraepithelial lesion and intraepithelial cancer. Due to a substantial overlap in percent free prostate specific antigen between the 2 groups, a clinically useful cutoff point could not be established. Therefore, we recommend repeat biopsy in all patients with high grade intraepithelial lesions regardless of the percent free PSA.

Adult↗

Detection of prostate carcinoma using prostate specific antigen, its density, and the density of the transition zone in Japanese men with intermediate serum prostate specific antigen concentrations.

BACKGROUND: This study was undertaken to determine whether the prostate specific antigen (PSA) density (PSAD) and PSAD of the transition zone (PSADT) are useful in the detection of prostate carcinoma in Japanese men with intermediate levels of serum PSA. METHODS: Two hundred and eighty-seven Japanese men with intermediate serum PSA levels (2.1 ng/mL to 10 ng/mL) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and systematic biopsy under TRUS guidance. The volume of the transition zone was also measured by TRUS in 134 patients. The PSAD and PSADT were determined for each patient, and their relationship to prostate carcinoma detection was examined. RESULTS: Prostate carcinoma was detected in 30 of 287 patients (10.5%). Although the serum PSA levels were similar in patients with benign and malignant prostate disease (P = 0.541), the prostate volume (P 0.0009) and PSAD (P < 0.0001) differed significantly in the two groups; in the patients with prostate carcinoma, the prostate volume was smaller, and the PSAD higher, than in the patients with benign disease. At the PSAD cutoff value of 0.18 ng/mL/cm3 or greater, the sensitivity was 70% and the specificity was 67% for the diagnosis of prostate carcinoma. The PSAD was found to be significantly better in the differentiation between benign and malignant prostate disease than the serum PSA in the receiver operating characteristic analyses (P = 0.045). However, the receiver operating characteristic curve for PSAD was not significantly different compared with that for PSA in the men with negative digital rectal examination findings. Prostate carcinoma was detected in 9.0% (12 of 134) of the patients who underwent PSADT determination. Receiver operating characteristic analyses showed that PSADT was not superior to PSA in the detection of prostate carcinoma. CONCLUSIONS: In Japanese men with intermediate serum PSA concentrations, PSAD offers additional information useful in the detection of prostate carcinoma, but PSADT does not. Although use of PSAD may decrease the number of unnecessary biopsies, a significant number of prostate carcinomas may be overlooked. Therefore, the authors recommend that serum PSA levels continue to be used as an indicator for biopsy in Japanese men.

Adult↗

Nomogram prediction for prostate cancer and aggressive prostate cancer at time of biopsy: utilizing all risk factors and tumor markers for prostate cancer.

BACKGROUND: There is a large amount of confusion in interpreting prostate specific antigen (PSA) values for prostate cancer. More precise risk assessments for prostate cancer detection are needed for men faced with an abnormal PSA. METHODS: We studied a sample of 2,637 men who underwent a prostate biopsy for an abnormal digital rectal exam (DRE) or PSA. Using factors including age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA, we constructed nomograms to predict the probability of prostate cancer at biopsy. RESULTS: Of the 2,637 men, 1,282 men (48.6%) had prostate cancer detected. Age, ethnicity, family history of prostate cancer, a previous negative biopsy, prostate volume, DRE and PSA were all significant predictors of prostate cancer. Nomograms were constructed based on these factors to predict the risk of prostate cancer and of aggressive prostate cancer (defined as a Gleason Score 7 or more). The positive predictive value varied from 5% to 95% based on the nomograms. The nomograms were validated using bootstrapping methods and the expected and observed proportions were found to be highly concordant. CONCLUSIONS: For men with an abnormal PSA or DRE, the risk for prostate cancer can be accurately estimated using a nomogram based on age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA. This tool will aid physicians and patients in determining the need for prostate biopsy.

Adult↗

Citrate concentrations in human seminal fluid and expressed prostatic fluid determined via 1H nuclear magnetic resonance spectroscopy outperform prostate specific antigen in prostate cancer detection.

PURPOSE: We compared the performance of citrate concentration measurements in unprocessed human semen and expressed prostatic secretions from controls and from patients with biopsy confirmed prostate cancer to that of prostate specific antigen testing with respect to specificity and sensitivity for prostate cancer detection. MATERIALS AND METHODS: Semen and expressed prostatic secretions were collected in biopsy proven, prostate cancer bearing and noncancer bearing cases. Citrate concentrations were determined by quantitative in vitro, high field, water suppressed proton nuclear magnetic resonance spectroscopy. Assessments of the diagnostic performance of citrate and prostate specific antigen results in our study populations were made by ROC curve analysis. RESULTS: Citrate was measured in samples from 61 participants, of whom 16 without and 21 with cancer donated semen, and 17 without and 7 with cancer donated expressed prostatic secretions. Mean citrate +/- SE compared to that in controls was 2.7-fold lower in patients with cancer samples in semen (132.2 +/- 30.1 vs 48.0 +/- 7.9 mM, p < 0.05) and expressed prostatic secretions (221.4 +/- 55.4 vs 81.5 +/- 36.0 mM, p < 0.05). ROC curve analysis showed that measurements of citrate in semen performed as well as measurements of citrate in expressed prostatic secretion for detecting prostate cancer (AUC 0.81, 95% CI 0.60 to 0.92 and AUC 0.73, 95% CI 0.38 to 0.90, respectively, p > 0.05). ROC curve analysis also showed that the measurement of citrate in either fluid outperformed prostate specific antigen measurement for detecting prostate cancer in these subjects (AUC 0.61, 95% CI 0.44 to 0.74). CONCLUSIONS: In vitro nuclear magnetic resonance spectroscopic measurement of the citrate concentration in semen or expressed prostatic secretions outperforms prostate specific antigen testing for detecting prostate cancer.

Aged↗

Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report.

We assessed the ability of 31phosphorus (31P) transrectal magnetic resonance spectroscopy to characterize normal human prostates as well as prostates with benign and malignant neoplasms. With a transrectal probe that we devised for surface coil spectroscopy we studied 15 individuals with normal (5), benign hyperplastic (4) and malignant (6) prostates. Digital rectal examination, transrectal ultrasonography and magnetic resonance imaging were used to aid in accurate positioning of the transrectal probe against the region of interest within the prostate. The major findings of the in vivo studies were that normal prostates had phosphocreatine-to-adenosine triphosphate (ATP) ratios of 1.2 +/- 0.2, phosphomonoester-to-beta-ATP ratios of 1.1 +/- 0.1 and phosphomonoester-to-phosphocreatine ratios of 0.9 +/- 0.1. Malignant prostates had phosphocreatine-to-beta-ATP ratios that were lower (0.7 +/- 0.1) than those of normal prostates (p less than 0.02) or prostates with benign hyperplasia (1.1 +/- 0.2, p less than 0.01). Malignant prostates had phosphomonoester-to-beta-ATP ratios (1.8 +/- 0.2) that were higher than that of normal prostates (p less than 0.02). Using the phosphomonoester-to-phosphocreatine ratio, it was possible to differentiate metabolically malignant (2.7 +/- 0.3) from normal prostates (p less than 0.001), with no overlap of individual ratios. The mean phosphomonoester-to-phosphocreatine ratio (1.5 +/- 0.5) of prostates with benign hyperplasia was midway between the normal and malignant ratios, and there was overlap between individual phosphomonoester-to-phosphocreatine ratios of benign prostatic hyperplasia glands with that of normal and malignant glands. To verify the in vivo results, we performed high resolution magnetic resonance spectroscopy on perchloric acid extracts of benign prostatic hyperplasia tissue obtained at operation and on a human prostatic cancer cell line DU145. The extract results confirmed the differences in metabolite ratios observed in vivo. We conclude that transrectal 31P magnetic resonance spectroscopy can characterize metabolic differences between the normal and malignant prostate.

Adult↗

Prognostic factors in patients with prostate cancer refractory to endocrine therapy: univariate and multivariate analyses including doubling times of prostate-specific antigen and prostatic acid phosphatase.

Although several prognostic factors have been discussed, multivariate analysis that includes tumor marker doubling time has not yet been examined in patients with prostate cancer refractory to endocrine therapy. A number of conventional prognostic factors including doubling times of prostate-specific antigen and/or prostatic acid phosphatase were examined in 56 prostate cancer patients who were refractory to endocrine therapy, using univariate and multivariate analyses. On univariate analysis, 6 parameters (doubling times of prostate-specific antigen and prostatic acid phosphatase at the time of refractory status, performance status, duration from beginning of endocrine therapy to prostate-specific antigen/prostatic acid phosphatase failure, mode of recurrence, the presence or absence of prostate-specific antigen/prostatic acid phosphatase normalization, and alkaline phosphatase) were shown to be significant prognostic factors. On multivariate analysis, only performance status and doubling times of prostate-specific antigen and prostatic acid phosphatase were significant. These observations showed that the doubling times of prostate-specific antigen and prostatic acid phosphatase, calculated at the time of prostate-specific antigen/prostatic acid phosphatase failure by estimating serial prostate-specific antigen or prostatic acid phosphatase, were a valuable prognostic factor in patients with prostate cancer refractory to endocrine therapy.

Acid Phosphatase↗

Effects of combination endocrine treatment on normal prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma.

AIMS: To investigate the effect of combination endocrine treatment (CET) or luteinising hormone releasing hormone agonist and flutamide on non-neoplastic prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. METHODS: The morphology, including the mitotic activity, of 12 radical prostatectomies from patients with prostatic adenocarcinoma pretreated for three months with CET was evaluated in haematoxylin and eosin stained sections and compared with an untreated age and stage matched control group. RESULTS: A differential effect on the non-neoplastic prostate was observed. In fact, the transition zone of the treated prostate showed simplification of the glandular lobules: the ducts and acini were small without undulations of the epithelial border and with a prominent basal cell layer. Within the peripheral zone there was inconspicuous branching of the ducts and acini which looked dilatated and lined by flattened atrophic epithelium. Prostatic intraepithelial neoplasia occurred in scattered ducts and acini in the peripheral zone of 10 of the 12 patients. The epithelial cell lining showed a prominent basal cell layer. A certain degree of secretory cell type stratification was always present. However, crowding was less evident than in the untreated prostate because of cytoplasmic clearing and enlargement as a result of coalescence of vacuoles. The treated adenocarcinomas had neoplastic acini which looked small and shrunken, and areas of individual infiltrating tumour cells separated by abundant interglandular connective tissue. The secretory cells of the nonneoplastic, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma lesions had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation, and cytoplasmic clearing. Apoptotic bodies were easily identifiable in all the cell layers. The lumina were rich in macrophages, sloughed secretory cells with degenerative features, and apoptotic bodies. Mitoses were not observed in any of the treated non-neoplastic prostate, prostatic intraepithelial neoplasia, or prostatic adenocarcinomas, whereas the mitotic frequency increased from non-neoplastic prostate through prostatic intraepithelial neoplasia up to prostatic adenocarcinomas in the untreated specimens. CONCLUSIONS: CET before radical prostatectomy causes regressive epithelial changes together with enhanced apoptosis and blocked mitotic activity.

Adenocarcinoma↗

Molecular staging of prostate cancer. II. A comparison of the application of an enhanced reverse transcriptase polymerase chain reaction assay for prostate specific antigen versus prostate specific membrane antigen.

Current imaging modalities used to stage prostate cancer clinically fail to detect extracapsular disease in a significant subset of patients. A molecular based peripheral blood assay using the reverse transcriptase polymerase chain reaction has recently been shown to be a highly sensitive staging modality for detecting extraprostatic disease preoperatively. The assay uses primers that are specific for prostate specific antigen (PSA). We compare the application of the reverse transcriptase polymerase chain reaction assay using primers specific for the human prostate specific membrane antigen with results obtained from the same specimens by reverse transcriptase polymerase chain reaction for PSA. Prostate specific membrane antigen, a recently cloned prostatic antigen, is a transmembrane glycoprotein that has been described as prostate specific. These assays were applied to ribonucleic acids extracted from the peripheral blood lymphocyte fraction of 80 patients with clinically localized prostate cancer. In addition, blood specimens from 20 female patients, 20 young male patients, 25 age-matched control men under treatment for benign prostatic hypertrophy and 20 men with established, untreated metastatic prostate cancer were tested. All 3 groups of noncancer patients had negative polymerase chain reactions for PSA as well as prostate specific membrane antigen. Of 20 metastatic prostate cancer patients 16 (80%) had positive polymerase chain reactions for PSA, while only 10 (50%) had positive results for prostate specific membrane antigen. Among the 80 patients with clinically localized disease (stages T1 to T2cN0M0), 27 and 19 had positive polymerase chain reaction for PSA and prostate specific membrane antigen, respectively, from blood specimens obtained preoperatively. Analyzing the final pathology in each patient with the reverse transcriptase polymerase chain reaction assay identified a significantly stronger correlation with tumor invasion using the results of the PSA test rather than the results of the prostate specific membrane antigen reverse transcriptase polymerase chain reaction test (67% versus 34% sensitivity for detecting capsular penetration, 87% versus 46% sensitivity for detecting disease to the surgical margin and 83% versus 16% sensitivity for detecting seminal vesicle invasion). In contrast to the reverse transcriptase polymerase chain reaction assay for PSA, a similar assay done for prostate specific membrane antigen did not correlate with pathological stage of prostate cancer.

Adenocarcinoma↗

Pre-treatment and post-treatment evaluation of prostatic adenocarcinoma for prostatic specific acid phosphatase and prostatic specific antigen by immunohistochemistry.

Prostatic specific acid phosphatase and prostatic specific antigen have been used as specific markers of prostatic adenocarcinoma in immunohistochemical studies, particularly when seeking the primary site of a poorly differentiated metastasis. We herein evaluate the effect of therapy on the persistence of these markers in surgically obtained tissues. Prostatic biopsies from 30 patients with adenocarcinoma of the prostate gland before and after treatment with orchiectomy alone, diethylstilbestrol, external beam radiation or combined radiation and diethylstilbestrol were studied for prostatic specific acid phosphatase and prostatic specific antigen using the indirect immunoperoxidase technique. The interval between biopsies ranged from 3 to 72 months, with an average of 28 months. All pre-treatment biopsies stained positively for prostatic specific acid phosphatase and prostatic specific antigen. Staining for prostatic specific antigen and prostatic specific acid phosphatase was seen easily in 29 of 30 post-treatment biopsies, while in 1 case infiltrating anaplastic cells surrounded by stroma showed staining for these antigens in an extremely small percentage of cells, which were overlooked easily unless examined carefully. In view of this small number of positively staining cells this case was designated as equivocal. While some cases demonstrated less intense staining in post-treatment biopsies compared to pre-treatment, this finding was by no means constant. With these primary antisera a higher percentage of cytologically malignant cells stained positively for prostatic specific acid phosphatase than for prostatic specific antigen in adjacent tissue sections in some cases. Prostatic specific acid phosphatase and prostatic specific antigen appear to be sensitive and persistent markers of prostatic adenocarcinoma despite morphologic changes accompanying various therapies.

Acid Phosphatase↗

Immunohistochemical localization of prostate-specific acid phosphatase and prostate-specific antigen in stage A2 adenocarcinoma of the prostate: prognostic implications.

Previous immunohistochemical studies with prostate-specific acid phosphatase and prostate-specific antigen documented the diagnostic value of these antigens in the identification of metastatic prostatic adenocarcinomas and in the differentiation of primary prostatic adenocarcinomas from poorly differentiated transitional cell carcinomas. Although attempts have been made to correlate immunostaining with degree of tumor differentiation, no study has directly assessed the relation of either prostate-specific acid phosphatase or prostate-specific antigen immunoreactivity of tumors with their biologic behavior. Nineteen patients with predominantly intermediate Gleason grade untreated stage A2 carcinomas of the prostate were studied by the unlabeled antibody immunoperoxidase technique for prostate-specific acid phosphatase and prostate-specific antigen in an attempt to identify those in whom the disease would progress without further therapeutic intervention. Of the 12 carcinomas with areas of either weak or negative prostate-specific acid phosphatase staining, nine progressed. Two of the seven carcinomas that did not have these foci of poor immunostaining also progressed. Although there was a trend for foci of poor immunoreactivity to predict tumor progression, the correlation was not significant. All seven patients who had tumor foci with weak or negative prostate-specific antigen immunostaining experienced progression of the disease. Of the 12 patients with only moderate or intense staining, the tumors did not progress in eight. This correlation between foci of poor immunoreactivity and progression of disease was statistically significant. When the study was repeated by varying the technique without awareness of previous grading results, the same predictive results were obtained. When results of prostate-specific antigen immunostaining were compared with those achieved with prostate-specific acid phosphatase, the superiority of the prostate-specific antigen antisera for labeling prostatic tissue was evident. This study suggests that prostatic cancers consist of subpopulations of cells with differing immunoreactive properties and that the presence of cells that lack sufficient differentiation to express normally present immunologically recognizable antigens is an indication of potentially more aggressive neoplasms.

Acid Phosphatase↗

Benign prostatic hyperplasia, prostate cancer and other prostate diseases diagnosed as a result of screening procedure among 1,004 men in the Lublin district.

Urological problems especially connected with prostate diseases appear in older men: prostatitis, benign prostatic hyperplasia, prostate cancer and others. Prostate cancer is the most common cancer in men and the second leading cause of deaths in male population. Therefore, it seems important to early detect prostate cancer in general practice setting due to screening procedures such as digital rectal exam and prostate-specific-antigen test. The aim of the study was to examine the character of diagnoses of a prostate disease among 1,004 men of the Lublin district who reported to a doctor during screening procedure carried out in urology outpatient clinic at Clinical Hospital in Lublin in the year 2000. After physical examination urologists initially diagnosed a prostate disease and sent men suspected to have a prostate cancer to further investigations. There was studied age and place of living. Benign prostate hyperplasia was the most common diagnosis made in 77.1% of subjects. It occurred most often in men aged 51-70 years. Prostate cancer was suspected in 3.5% of subjects. Frequency of benign prostate hyperplasia and prostate cancer suspicion increased with age. On the basis of studies screening procedures seem beneficial in the early detection of prostate cancer in men over 50.

Adult↗

Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer.

Isolated prostate specific antigen (PSA) determinations in asymptomatic individuals have not demonstrated sufficient sensitivity and specificity to be useful in the routine evaluation of prostate disease. To enhance the accuracy of serum PSA we have used a quotient of serum PSA and prostate volume, which we refer to as prostate specific antigen density (PSAD). Prostate volume in this study was calculated from magnetic resonance imaging determinations of benign prostatic hypertrophy (BPH) or from the dimensions of the surgical specimen of cancer using the formula, length x width x depth x 0.5 = volume. A total of 61 patients with prostatic disease clinically confined to the prostate glands (41 with prostate cancer undergoing radical prostatectomy and 20 with BPH) was evaluated. The mean PSAD for prostate cancer was 0.581 while that for BPH was 0.044 (p less than 0.002). No patient with BPH had a PSAD of greater than 0.117 and only 1 patient had a density of 0.1 or greater. Of 34 patients with a PSAD of 0.1 or greater 33 had prostate cancer. Only 2 of the 41 prostate cancer patients and 14 of the BPH patients had a PSAD of 0.05 or less. There were 11 patients with a PSAD of greater than 0.05 and less than 0.1, including 6 with prostate cancer (1 with P0 disease) and 5 with BPH. Of the 6 prostate cancer patients 5 had a PSA of 4.0 or less and among the 5 patients with BPH 4 had a serum PSA of greater than 4.0 and 1 had a PSA of greater than 10. These results suggest that PSAD may be useful in distinguishing BPH and prostate cancer.

Antigens, Neoplasm↗

Usefulness of digital rectal examination, serum prostate-specific antigen, transrectal ultrasonography and systematic prostate biopsy for the detection of organ-confined prostate cancer.

The detection rate of organ-confined prostate cancer by digital rectal examination (DRE), serum prostate-specific antigen (PSA), and transrectal ultrasound (TRUS) of the prostate, as well as the value of a directed, guided transrectal core biopsy for the prostate (TRUS-guided biopsy) combined with systematic biopsy, were evaluated. The subjects were 171 patients with urinary symptoms suggestive of prostatic disease excluding those with clinical stage C and D prostate cancer. Twenty-five patients (14.6%) had prostate cancer, 127 (74.2%) had benign prostate hypertrophy, four (2.3%) had prostatic intraepithelial neoplasia, eleven (6.4%) had inflammation, and four (2.3%) had normal prostate tissue. The incidence of detection of hypoechoic findings by TRUS in the patients in whom nodules were detected by DRE or who had elevated serum PSA was higher than that in patients with negative diagnostic findings. In 22 of the 25 patients with prostate cancer, the cancer was detected by recognition of a hypoechoic area on TRUS. In 10 of these 22 patients, prostate cancer was also detected by systematic biopsy in isoechoic areas. Prostate cancer was detected by systematic biopsy in three patients without hypoechoic findings. The positive predictive value for patients with abnormal findings on all three tests was 64.3%, which is significantly higher than that for patients with any other combination of findings (p < 0.05). Our results indicate that the combination of DRE, serum PSA and TRUS is useful for the detection of organ-confined prostate cancer, and that TRUS and TRUS-guided prostate biopsy combined with systematic biopsy should be performed in patients with abnormal findings for both DRE and PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗