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Can prostate-specific antigen reverse transcriptase-polymerase chain reaction be used as a prospective test to diagnose prostate cancer?

The present study addressed the question as to whether prostate-specific antigen reverse transcriptase-polymerase chain reaction (PSA RT-PCR) could be used to identify prospectively men who have prostate cancer and to help determine which patients with an initially negative biopsy would benefit from rebiopsy. PSA RT-PCR was performed prospectively on 90 patients who were to have a prostate biopsy because of an elevated PSA level, an abnormal digital rectal examination, or both. PSA RT-PCR was performed, and the sensitivity of the test was enhanced by hybridization of the PCR with a 32P-labeled PSA cDNA probe (exons 3-5). Of the 90 men, 36 (40%) had prostate cancer on biopsy. Of these 36 men, 5 (13.9%) had a positive PSA RT-PCR finding, whereas 31 (84.1%) tested negative. Of 54 men with negative biopsies, 8 (14.8%) had a positive PSA RT-PCR result. The sensitivity of PSA RT-PCR for the detection of biopsy-proven prostate cancer was 13.9% and the specificity was 85.2%. Only 3 of 12 (25%) patients with advanced disease had a positive test result. The sensitivity of PSA RT-PCR for the detection of biopsy-proven prostate adenocarcinoma in men suspected of having prostate cancer is poor. Indeed, men without biopsy-proven prostate cancer are just as likely to have a positive result in the PSA RT-PCR as are men with cancer. Whether these men with negative prostate biopsies and positive PSA RT-PCR findings may eventually develop prostate cancer remains to be determined. At this time, PSA RT-PCR for the prospective detection of prostate cancer should be considered investigational.

Adenocarcinoma↗

Differential expression of human leukocyte antigen-G (HLA-G) messenger RNAs and proteins in normal human prostate and prostatic adenocarcinoma.

Human leukocyte antigen-G (HLA-G) is a major histocompatibility complex class Ib gene expressed in normal organs and in some tumors. The glycoproteins encoded by this gene are best known for their immunosuppressive properties. Because isoform-specific expression of HLA-G in male reproductive organs has not been reported, we investigated HLA-G1, -G2, -G5, -G6 mRNAs and proteins in four-to-five samples of normal prostate glands, prostates with benign prostatic hyperplasia and prostate adenocarcinomas using RT-PCR and immunohistochemistry. All tissues contained HLA-G1, -G2, -G5 and -G6 specific mRNAs, but only HLA-G5 protein was detectable. In normal prostate glands, HLA-G5 protein was prominent in the cytoplasm of tubuloglandular epithelia and in glandular secretions. Staining was reduced in samples of benign prostatic hyperplasia but remained localized to the cytoplasm of glandular epithelia and secretions. In prostatic adenocarcinomas, HLA-G5 protein was detectable mainly in the secretions. Thus, HLA-G5 but not HLA-G1, -G2 or -G6 is produced in the normal prostate and is present in prostatic secretions. In addition, normal cellular localization is disturbed in benign and malignant prostatic adenocarcinomas. The results are consistent with this molecule may influencing female immune receptivity to sperm and suggest that such immunosuppression could be disturbed in men with prostatic adenocarcinomas.

Adenocarcinoma↗

Detectable prostate specific antigen between 60 and 120 days following radical prostatectomy for prostate cancer: natural history and prognostic significance.

PURPOSE: Following radical retropubic prostatectomy for prostate cancer, if the serum prostate specific antigen fails to become undetectable, occult micrometastatic disease is suspected. We assessed the natural history of disease progression, and predictors of recurrence and survival in this group of patients. MATERIALS AND METHODS: We identified 303 men treated with radical retropubic prostatectomy for prostate cancer between 1990 and 1999, who had a detectable prostate specific antigen between 60 and 120 days postoperatively. Systemic recurrence-free and cancer specific survival were estimated using the Kaplan-Meier method, and analyzed using Cox proportional hazards models. RESULTS: Clinical and pathological features were more adverse among men whose postoperative prostate specific antigen was detectable. These men had poorer systemic recurrence-free survival and cancer specific survival compared to men with an undetectable postoperative prostate specific antigen, and even men whose prostate specific antigen subsequently became detectable. These differences persisted after multivariate adjustment for preoperative prostate specific antigen, specimen Gleason score, seminal vesicle and margin status. With a median followup of 8.5 years, 50 systemic recurrences and 26 deaths from cancer were observed. Gleason score and the prostate specific antigen doubling time were multivariate predictors of systemic recurrence, while Gleason score, margin status and seminal vesicle invasion were predictors of death from cancer. CONCLUSIONS: A detectable prostate specific antigen immediately following radical retropubic prostatectomy confers an increased risk of progression and death, but only in a subset of patients, who may be identified on the basis of pathological features and prostate specific antigen doubling time. In future such patients may be suitable for trials of systemic therapy.

Adult↗

DNA methylation paradigm shift: 15-lipoxygenase-1 upregulation in prostatic intraepithelial neoplasia and prostate cancer by atypical promoter hypermethylation.

Fifteen (15)-lipoxygenase type 1 (15-LO-1, ALOX15), a highly regulated, tissue- and cell-type-specific lipid-peroxidating enzyme has several functions ranging from physiological membrane remodeling, pathogenesis of atherosclerosis, inflammation and carcinogenesis. Several of our findings support a possible role for 15-LO-1 in prostate cancer (PCa) tumorigenesis. In the present study, we identified a CpG island in the 15-LO-1 promoter and demonstrate that the methylation status of a specific CpG within this island region is associated with transcriptional activation or repression of the 15-LO-1 gene. High levels of 15-LO-1 expression was exclusively correlated with one of the CpG dinucleotides within the 15-LO-1 promoter in all examined PCa cell-lines expressing 15-LO-1 mRNA. We examined the methylation status of this specific CpG in microdissected high grade prostatic intraepithelial neoplasia (HGPIN), PCa, metastatic human prostate tissues, normal prostate cell lines and human donor (normal) prostates. Methylation of this CpG correlated with HGPIN, PCa and metastatic human prostate tissues, while this CpG was unmethylated in all of the normal prostate cell lines and human donor (normal) prostates that either did not display or had minimal basal 15-LO-1 expression. Immunohistochemistry for 15-LO-1 was performed in prostates from PCa patients with Gleason scores 6, 7 [(4+3) and (3+4)], >7 with metastasis, (8-10) and 5 normal (donor) individual males. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect 15-LO-1 in PrEC, RWPE-1, BPH-1, DU-145, LAPC-4, LNCaP, MDAPCa2b and PC-3 cell lines. The specific methylated CpG dinucleotide within the CpG island of the 15-LO-1 promoter was identified by bisulfite sequencing from these cell lines. The methylation status was determined by COBRA analyses of one specific CpG dinucleotide within the 15-LO-1 promoter in these cell lines and in prostates from patients and normal individuals. Fifteen-LO-1, GSTPi and beta-actin mRNA expression in BPH-1, LNCaP and MDAPCa2b cell lines with or without 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin-A (TSA) treatment were investigated by qRT-PCR. Complete or partial methylation of 15-LO-1 promoter was observed in all PCa patients but the normal donor prostates showed significantly less or no methylation. Exposure of LNCAP and MDAPCa2b cell lines to 5-aza-dC and TSA resulted in the downregulation of 15-LO-1 gene expression. Our results demonstrate that 15-LO-1 promoter methylation is frequently present in PCa patients and identify a new role for epigenetic phenomenon in PCa wherein hypermethylation of the 15-LO-1 promoter leads to the upregulation of 15-LO-1 expression and enzyme activity contributes to PCa initiation and progression.

Adult↗

Can effect of finasteride on prostate-specific antigen be used to decrease repeat prostate biopsy?

OBJECTIVES: Patients often undergo multiple prostate biopsies for persistently elevated prostate-specific antigen (PSA) levels. Finasteride decreases serum PSA by approximately 50%. We performed a pilot study to examine the correlation among finasteride, PSA, and PSA density (PSAD) to identify patients who could be excluded from repeat prostate biopsy. METHODS: We performed a prospective study from 2001 to 2002 on 25 men with elevated PSA levels. These patients had prior negative prostate biopsy findings. At study onset, the patients' PSA level and PSAD were measured. Patients were instructed to take finasteride 5 mg for 6 months. PSA and PSAD determination and prostate biopsies were repeated at 6 months and the findings compared with the initial results. RESULTS: The mean patient age was 67.2 years (median 62). The median PSA level was 8.3 ng/dL at study entry (mean 9.34) and 4.6 ng/dL (mean 5.09) at 6 months. The median PSAD was 0.18 (mean 0.20) at study entry and 0.09 (mean 0.12) at 6 months. Of the 23 patients who completed the study, 6 (26%) were diagnosed with prostate cancer. At study entry, the median PSA level in those with prostate cancer was 9.6 ng/dL and was 5.8 ng/dL at 6 months. Patients without prostate cancer on repeat biopsy had a 44% decrease in PSAD. Patients with prostate cancer had a 5% decrease in PSAD. CONCLUSIONS: The results of our study have demonstrated that patients without prostate cancer have a greater decrease in PSAD when taking finasteride than those with prostate cancer. This pilot study had a small population with limited power, and a repeat prospective study with a larger population is warranted.

Aged↗

15-lipoxygenase-2 (15-LOX-2) is expressed in benign prostatic epithelium and reduced in prostate adenocarcinoma.

Human 15S-lipoxygenase-2 (15-LOX-2) is a recently identified lipoxygenase that has approximately 40% sequence identity to the known human 5S-, 12S-, and 15S-lipoxygenases. 15-LOX-2 has a limited tissue distribution, with mRNA detected in prostate, lung, skin, and cornea, but not in numerous other tissues, including peripheral blood leukocytes. In the current study, we have characterized the distribution of 15-LOX-2 in the human prostate by immunohistochemistry, demonstrated the ability of benign prostate tissue to form 15S-hydroxyeicosatetraenoic acid (15S-HETE) from exogenous arachidonic acid (AA), and begun characterizing possible alterations in 15-LOX-2 in prostate adenocarcinoma. Incubation of benign prostate tissue with [14C]AA resulted in formation of [14C]15-HETE, as determined by reverse- and straight-phase high-performance liquid chromatography. 15-HETE was the major AA metabolite formed. By immunohistochemistry, 15-LOX-2 is located in secretory cells of peripheral zone glands and large prostatic ducts and somewhat less uniformly in apical cells of transition and central zone glands. 15-LOX-2 was not detected in the basal cell layer, stroma, ejaculatory ducts, seminal vesicles, or transitional epithelium. Immunostaining of 18 radical prostatectomy specimens showed a loss of 15-LOX-2 in the majority of prostate adenocarcinomas; 14 of 18 cases showed loss of 15-LOX-2 in >25% of the tumor (mean, 74.9% negative for 15-LOX-2; range, 38.9% to 100%). Incubation of paired pure benign and pure malignant prostate tissue from the same radical prostatectomies showed that 15-HETE formation was markedly reduced (>90%) or undetectable in incubations of prostate adenocarcinoma. 15-LOX-2 is a novel human lipoxygenase with a limited tissue distribution that is strongly expressed in benign prostate glandular epithelium and lost to a variable degree in the majority of prostate adenocarcinomas.

Adenocarcinoma↗

Reconstruction of prostatic acinus-like structure from ventral and dorsolateral prostatic epithelial cells of the rat in three-dimensional collagen gel matrix culture.

PURPOSE: The study was carried out to reconstruct a prostatic acinus-like structure from prostatic epithelial cells in a new culture system which can provide a more physiological condition than conventional cell culture methods. MATERIALS AND METHODS: Prostatic epithelial cells were isolated from ventral and dorsolateral prostates of the rat and were separately cultured in three-dimensional collagen gel matrix. The cultured cells were observed by photo-microscopy and transmission electron microscopy. Differentiation and proliferation of the cultured cells were examined by immunohistochemistry using PAP and PSA kits and a bromodeoxy-uridine (BrdU) kit. The cell area of acinus-like structures in the transverse sections was measured by computer with the Interaktive Bild-Analyse System. RESULTS: Dissociated prostatic epithelial cells were organized into three-dimensional spherical or branching cellular aggregates in collagen gel matrix. Through cell proliferation and differentiation, the cellular aggregates formed prostatic acinus-like structures, which consisted of a small intercellular lumen enclosed by one layer of cuboidal epithelial cells. The epithelial cells were connected together by junctional complexes, had microvilli at the luminal surface, and the basal side was surrounded by a distinct basal lamina. In the lumina of acinus-like structures, secretory products were often found. CONCLUSIONS: Prostatic acinus-like structures were reconstructed from dissociated prostatic epithelial cells in three-dimensional collagen gel matrix culture. The reconstructed acinus-like structures are similar to prostatic acini in vivo in structure and function. This three-dimensional collagen gel matrix culture model may provide a useful means for investigating prostatic diseases and influences that hormones and growth factors exert on prostatic epithelial cells.

Acid Phosphatase↗

Prostatic intraepithelial neoplasia: influence of clinical and pathological data on the detection of prostate cancer.

PURPOSE: We attempted to characterize patients diagnosed with prostatic intraepithelial neoplasia without concurrent cancer on biopsy who had prostate cancer on subsequent biopsy. MATERIALS AND METHODS: The records of 93 patients with low and high grade prostatic intraepithelial neoplasia without concurrent cancer on initial biopsy were analyzed. The relationships among prostatic intraepithelial neoplasia grades, patient age, digital rectal examination, serum prostate specific antigen (PSA), transrectal ultrasound appearance and final pathological results were investigated. RESULTS: Subsequent carcinoma was found on repeat biopsy in 13.3% of patients with low grade and 47.9% with high grade prostatic intraepithelial neoplasia (p < 0.001). In the former group digital rectal examination, patient age, serum PSA and transrectal ultrasound were not predictive of cancer. Transrectal ultrasound appearance, digital rectal examination and serum PSA were statistically different between high grade prostatic intraepithelial neoplasia with and without subsequent cancer (p < 0.001, p = 0.008 and p = 0.016, respectively, univariate analysis). On multivariate analysis of patients with high grade prostatic intraepithelial neoplasia only digital rectal examination and PSA were predictive of subsequent carcinoma. CONCLUSIONS: High grade prostatic intraepithelial neoplasia is a strong predictor of subsequent cancer, especially in men with abnormal digital rectal examination and elevated serum PSA. Patients with high grade prostatic intraepithelial neoplasia should undergo repeat biopsy to exclude cancer. Further investigations are needed to optimize the treatment of patients with low grade prostatic intraepithelial neoplasia.

Aged↗

Serum triiodothyronine is increased in men with prostate cancer and benign prostatic hyperplasia.

UNLABELLED: Triiodothyronine is the active thyroid hormone produced by de-iodination of the precursor thyroxine that is necessary for the growth of prostate cancer cells in vitro. For this reason we assessed serum triiodothyronine levels in men with localized prostate cancer, benign prostatic hyperplasia (BPH) and controls in the same age group. MATERIALS AND METHODS: We studied 161 men referred for treatment of localized prostate cancer, 20 with BPH and 27 controls. Serum triiodothyronine was determined by fluorometric immunoassay and a commercially available instrument. RESULTS: Men with BPH had the highest triiodothyronine levels, followed by those with prostate cancer. Controls had the lowest triiodothyronine. There was significant triiodothyronine variation among the 3 groups (1-way ANOVA p = 0.001). In men with BPH serum triiodothyronine was significantly different from that in men with prostate cancer (Tukey's multiple range test p = 0.013). Men with prostate cancer had serum triiodothyronine that was significantly different than in controls (p = 0.048), as did those with BPH (p <0.001). Because serum triiodothyronine normally decreases with age, we performed multivariate analysis of variance controlling for age. There was a significant decrease in serum triiodothyronine with age (p = 0.020). There was also significant triiodothyronine variation among the 3 subject groups independent of age (p <0.001). CONCLUSIONS: Urologists are actively seeking additional biomarkers of prostate cancer aggressiveness. Many prostate cancers are quite indolent and may never cause a problem but it is impossible to identify such tumors with certainty. With more and better biomarkers many older men with prostate cancer may be spared the rigors of radiation therapy and/or surgery as well as complications. Triiodothyronine may be such a biomarker. Also, new prostate cancer and BPH therapies may be directed toward inhibiting the mitogenic effects of triiodothyronine.

Biomarkers↗

An adequate sampling of the prostate to identify prostatic involvement by urothelial carcinoma in bladder cancer patients.

The distribution of any involved prostatic urethra, ducts and acini by urothelial carcinoma was studied to determine an adequate sampling method for detecting prostatic involvement using the maps of 38 cystoprostatectomy specimens. A total of 31 patients had prostatic duct and acini involvement, while 7 had prostatic urethral involvement alone. However, the distribution of the involved prostatic urethra, ducts and acini varied. In 29 of the 31 patients (93.5%) with prostatic duct and acini involvement, urethral carcinoma in situ and/or superficial gland involvement (an involvement of the afferent ducts within a few millimeters of the urethral mucosa) at the 5 and/or 7 o'clock position of the verumontanum portion was identified. In 7 patients with prostatic urethral involvement alone 2 had carcinoma foci at the 5 and/or 7 o'clock position of the verumontanum portion. Furthermore, the frequency of deeper gland involvement (an involvement of true prostatic acini except for superficial glands) was higher in patients with superficial gland involvement at the 5 and/or 7 o'clock position of the verumontanum portion (57.7%) than in patients without such involvement (20.0%). Therefore, this study emphasizes that a transurethral resection biopsy containing prostatic tissue at the 5 and/or 7 o'clock position of the verumontanum portion substantially improves the detection of prostatic duct and acini involvement in bladder cancer patients. Moreover, if the prostatic superficial glands are involved at the 5 and/or 7 o'clock position of the verumontanum portion, the potential involvement of the deeper glands should also be suspected.

Carcinoma in Situ↗

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. I. Untreated patients.

Serum prostate specific antigen levels were determined (Yang polyclonal radioimmunoassay) in 230 men with untreated adenocarcinoma of the prostate after careful clinical staging. Prostate specific antigen was directly proportional to advancing clinical stage, statistically failing to distinguish only between consecutive stages B2 and B3, and between stages C and D1. Serum prostatic acid phosphatase by radioimmunoassay was unable to distinguish men with stages C plus D1 from B2 plus B3 disease but it could distinguish stages C plus D1 from A2 plus B1 (p equals 0.015). Serum prostate specific antigen was directly proportional to increasing Gleason score. In 59 untreated patients multiple prostate specific antigen values were obtained during a mean followup of 10 months. Of the patients 81 per cent showed a steady increase with time, including 91 per cent of men with clinical stage B2 or greater disease. The rate of increase accelerated with time, and correlated with advancing tumor stage and increasing serum concentration of prostate specific antigen. The rate of increase of prostate specific antigen in clinical stages A and B cancer patients suggested a doubling time of at least 2 years. Serum prostate specific antigen was significantly decreased by transurethral resection of prostatic tissue in patients with cancer, as has been shown previously in patients with benign prostatic hyperplasia.

Adenocarcinoma↗

Flow cytometric analysis of comedocarcinoma of the prostate: an uncommon histopathological variant of prostatic adenocarcinoma.

Pathological data from 321 patients who underwent radical prostatectomy or cystoprostatectomy with a diagnosis of prostatic adenocarcinoma were reviewed. Of these specimens 4 (1.2 per cent) demonstrated histopathological findings consistent with prostatic comedocarcinoma. Prostatic acid phosphatase and prostate specific antigen detected by immunoperoxidase technique confirmed the prostatic origin of all comedocarcinomas studied. Flow cytometric analysis of deparaffinized sections from these specimens as well as a total of 40 representative specimens from normal prostate, and low, intermediate and high grade prostatic carcinomas was performed. Frequency of aneuploidy in low, intermediate and high grade prostatic adenocarcinoma was 0, 43 and 75 per cent, respectively. All cases of prostatic comedocarcinoma studied had distinctly aneuploid deoxyribonucleic acid histograms and the mean deoxyribonucleic acid content in comedocarcinoma was the highest of all groups analyzed. The mean time to recurrence in patients with comedocarcinoma was 13 months. Our flow cytometric data suggest that prostatic comedocarcinoma represents a potentially aggressive tumor demonstrating cytogenetic aberration shown to be associated with poor clinical outcome in prostatic adenocarcinoma.

Aged↗

Age-related changes in tissue levels of prostatic acid phosphatase and prostate specific antigen.

Immunoperoxidase localization of prostatic tissue antigens has become useful in identifying the prostate as the origin of metastatic disease. Much research has been aimed at investigating the presence of these antigens in the adult prostate gland in benign and neoplastic states. Few studies have been done to determine the presence of these markers before puberty. We studied the prostate gland of 42 children of varying ages to determine the presence of these antigens at all age ranges to puberty. Sequential sections of the prostate were cut for prostate specific antigen, prostatic acid phosphatase, and hematoxylin and eosin staining. The degree of immunoperoxidase stain was graded from 0 to 4. The results showed that staining levels of prostate specific antigen and prostatic acid phosphatase were high at birth, decreased by age 6 months, reappeared by age 10 years and increased to puberty. Thus, the levels of prostate specific antigen and prostatic acid phosphatase appear to follow the testosterone levels, suggesting a hormonal dependence.

Acid Phosphatase↗

Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia.

Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. Recently PTHrP has been shown to be an early-response gene that may be involved in cellular proliferation or differentiation. In addition, PTHrP has been implicated in the pathogenesis of bone metastases. Bone metastases are a significant complication in patients with prostate cancer. We compared the expression of PTHrP by immunohistochemical staining using a monoclonal antibody directed against epitope between amino acids [53-64] in benign prostatic hyperplasia (BPH) with that in various stages of prostate cancer. Tissue sections were obtained on formalin-fixed paraffin-embedded blocks from BPH, well-differentiated prostate cancer, poorly differentiated prostate cancer, lymph node metastases (n = 15 each), and normal prostate (n = 2). In the normal prostate tissue there was no staining observed. In BPH, 13 of 15 tissue samples were positive for PTHrP immunoreactivity. An average of 33% of the cells stained positive with 1+ intensity. All samples from prostate cancer stained positive for PTHrP. In the samples from well-differentiated prostate cancer, an average of 87% of cells stained positive for PTHrP, whereas 100% of cells were positive in poorly differentiated and metastatic tumors. The intensity of staining was 3+ in well-differentiated tumors and 4+ in poorly differentiated tumors. Therefore, the expression of PTHrP is enhanced in prostate cancer as compared with BPH and is greater in poorly differentiated carcinoma as compared with the well-differentiated tumors. The role of PTHrP in the pathogenesis of prostate cancer deserves further study.

Adult↗

Distinguishing chronic prostatitis and benign prostatic hyperplasia symptoms: results of a national survey of physician visits.

OBJECTIVES: The morbidity of chronic prostatitis results from a constellation of genitourinary symptoms. A recent study classified 21 of these symptoms into three categories: pain, voiding complaints, and sexual dysfunction. Pain symptoms predominated among patients with prostatitis. Using data from a nationwide survey of physician visits, we examined the most common symptoms reported by men at chronic prostatitis visits and contrasted the results with visits for benign prostatic hyperplasia (BPH). METHODS: We analyzed 81,034 visits by men (18 years and older) to office-based physicians of all specialties in the National Ambulatory Medical Care Surveys of 1990 to 1996, using sampling weights to make national estimates. U.S. physicians selected by random stratified sampling completed visit forms that included patients' reasons for visits and physicians' diagnoses. RESULTS: In 1990 to 1996, there were 765 visits (national estimate 1.5 million visits/yr; 95% confidence interval = 0.9 to 2.1) with a diagnosis of chronic prostatitis. Among chronic prostatitis visits, 20% were for pain, 19% for urinary symptoms, and 1% for sexual dysfunction. Among 2271 BPH visits, 2% were for pain, 33% for voiding complaints, and 1% for sexual dysfunction. The most common reason coded for chronic prostatitis visits was painful urination (14% of chronic prostatitis visits, but only 1.7% of BPH visits). CONCLUSIONS: Pain was slightly more common than voiding complaints, but much more common than sexual dysfunction among chronic prostatitis visits. The most common reason for chronic prostatitis visits was painful urination, which was uncommon among patients with BPH. Pain distinguished chronic prostatitis from BPH better than any other urinary symptom.

Adult↗

Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group.

OBJECTIVES: Prostate-specific antigen (PSA) is produced exclusively in the prostate gland and is currently the most useful clinical marker for the detection of prostate cancer. In this report, we examine whether serum PSA is also a predictor of important benign prostatic hyperplasia (BPH)-related outcomes, acute urinary retention (AUR), and the need for BPH-related surgery. METHODS: Three thousand forty men were treated with either placebo or finasteride in a double-blind, randomized study of 4-year duration. Serum PSA was measured at baseline, and baseline prostate volume was measured in a 10% subset of 312 men. Probabilities and cumulative incidences of AUR and BPH-related surgery, as well as reduction in risk of events with finasteride, were calculated for the entire patient population, stratified by treatment assignment, baseline serum PSA, and prostate volume. RESULTS: The risk of either needing BPH-related surgery or developing AUR ranged from 8.9% to 22.0% during the 4 years in placebo-treated patients stratified by increasing prostate volume and from 7.8% to 19.9% when stratified by increasing serum PSA. In comparison with symptom scores, flow rates, and residual urine volume, receiver operating characteristic curve analyses showed that serum PSA and prostate volume were the most powerful predictors of spontaneous AUR in placebo-treated patients (area under the curve 0.70 and 0.81, respectively). Finasteride treatment reduced the relative risk of needing surgery or developing AUR by 50% to 74% and by 43% to 60% when stratified by increasing prostate volume and serum PSA, respectively. CONCLUSIONS: Serum PSA and prostate volume are powerful predictors of the risk of AUR and the need for BPH-related surgery in men with BPH. Knowledge of baseline serum PSA and/or prostate volume are useful tools to aid physicians and decision makers in predicting the risk of BPH-related outcomes and choosing therapy for BPH.

Acute Disease↗

Human prostate-specific transglutaminase gene: promoter cloning, tissue-specific expression, and down-regulation in metastatic prostate cancer.

OBJECTIVES: To investigate the tissue-specific and differential expression of the human prostate-specific transglutaminase (pTGase) gene in metastatic prostate cancer (CaP) and to study how this gene is regulated in the prostate. METHODS: Northern blot hybridization and polymerase chain reaction (PCR) were performed using RNA from a variety of organs to confirm prostate-specific expression of the gene. Relative quantitative reverse transcriptase-PCR (RT-PCR) was performed to investigate the differential expression of the gene among normal prostates and prostates with CaP and metastatic CaP. The pTGase gene promoter was cloned using genomic library screening and sequencing. Transfection experiments and chloramphenicol acetyltransferase (CAT) assays were performed to study the regulation of the gene. RESULTS: Northern hybridization and RT-PCR confirmed that the gene is only expressed in the prostate. Relative quantitative RT-PCR demonstrated a loss of expression of the pTGase gene among men with CaP and higher Gleason grades. In metastatic CaP tissue from various sites, 86% of the samples lost expression of the gene. We cloned and sequenced a 1.4-kilobase promoter region of the pTGase gene. Transfection and CAT assay results supported the theory that certain elements in the -1 to -520 region are sufficient to direct prostate-specific expression of the gene. Additional elements in the -520 to -1400 region may also contribute to its prostate-specific expression. CONCLUSIONS: The results of our study demonstrate that the human pTGase gene is only expressed in prostate tissue and that its expression is inhibited in most metastatic CaP. Prostate-specific expression of the gene is controlled by elements in the promoter region. The observed preferential loss of pTGase gene expression in metastatic CaP may be important to the pathogenesis and progression of this disease.

Base Sequence↗

Increased prostatic blood flow in response to microwave thermal treatment: preliminary findings in two patients with benign prostatic hyperplasia.

OBJECTIVES: To determine the effects on prostate blood flow of heat generated by microwave thermal treatment in patients with benign prostatic hyperplasia. METHODS: Prostate blood flow was evaluated by continuous transrectal color Doppler ultrasonography in 2 patients at baseline, after implantation of interstitial needles used for thermal mapping, and during microwave thermal treatment. Temperatures at 30 prostatic, periprostatic, urethral, and rectal sites were continuously monitored. In 1 patient, transrectal prostate compression was applied and the blood flow and temperature response to this maneuver noted. RESULTS: Microwave thermal treatment achieved maximum prostate temperatures of 59 degrees C at 5 mm radially from the urethra. Urethral and rectal temperatures remained low. Marked increases occurred in prostate blood flow in response to microwave thermal treatment. These increases were apparent throughout the prostate gland, with the greatest increase in perfusion occurring in the peripheral zone and the posterior half of the transitional zone. After 15 minutes of microwave treatment, peak systolic blood flow increased 99% and 70% in patients 1 and 2, respectively, while end-diastolic blood flow climbed 50% and 112%, respectively. Prostate compression resulted in a prompt quenching of blood flow and an increase in prostate temperature. CONCLUSIONS: Based on these preliminary findings in 2 patients, prostate blood flow increases markedly in response to microwave thermal treatment. This compensatory increase in blood flow is likely to be a significant treatment-limiting factor in achieving effective thermoablation.

Blood Flow Velocity↗