PubMed Health⌕ Search

Biomedical subjects

Leonard S Marks

Publications and source records attributed to Leonard S Marks.

At least 19 recordsLinked to original sources
PubMed2025

Genomic and Transcriptomic Profiling of Radiation-Resistant, Locally Recurrent Prostate Cancer.

PURPOSE: The biology of locally radiorecurrent prostate cancer (LRR-PCa) is poorly understood. METHODS AND MATERIALS: We sought to explore the genomic and transcriptomic landscape of LRR-PCa with targeted DNA sequencing and RNA expression analysis from 41 biopsy-proven LRR-PCa tumors from 36 unique patients who had a recurrence at a median interval of 84 months (IQR, 70-124 months). Genomic alteration frequencies and transcriptomic data were compared between the LRR-PCa cohort and treatment-na&#xef;ve patients from the Cancer Genome Atlas (genomic; n = 496) and Gleason grade-at-recurrence-matched patients from the Decipher Genomics Resource for Intelligent Discovery (transcriptomic; n = 22,320). RESULTS: Twenty-five patients (69%) had pathologic upgrading at recurrence (17% vs 64% with Gleason grade 4-5 disease; P < .001). The LRR-PCa cohort demonstrated significantly greater single-nucleotide variations in 29 genes known to be associated with prostate cancer, including several associated with increased aggressiveness and DNA repair: FAT1 (58.5% vs 1.0%), RAD51B (36.6% vs 0.4%), POLQ (34.1% vs 1.4%), KMT2C (34.1% vs 4.9%), BRCA2 (29.3% vs 1.8%), ATRX (26.8% vs 0.8%), and BRCA1 (24.4% vs 0.4%) (Pvalues < .001 for all). The LRR-PCa cohort had a significantly higher Decipher score (median, 0.80 vs 0.66; P = .05) and demonstrated significantly greater basal subtype based on PAM50 (56% vs 20%; P < .001) and lower androgen receptor activity (61% for LRR vs 9%; P < .001). CONCLUSIONS: Overall, these results suggest that LRR-PCa has a distinct genomic and transcriptomic landscape from de novo prostate cancer. Specifically, LRR-PCa has an enrichment in SNVs in genes associated with tumor aggressiveness and/or DNA repair, has higher Decipher scores, a more basal subtype, and has transcriptomic evidence of lower androgen receptor activity and loss of tumor suppressor genes.

Humans↗
PubMed2006

Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial.

CONTEXT: Prostate safety is a primary concern when aging men receive testosterone replacement therapy (TRT), but little information is available regarding the effects of TRT on prostate tissue in men. OBJECTIVE: To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 44 men, aged 44 to 78 years, with screening serum testosterone levels lower than 300 ng/dL (<10.4 nmol/L) and related symptoms, conducted at a US community-based research center between February 2003 and November 2004. INTERVENTION: Participants were randomly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was the 6-month change in prostate tissue androgen levels (testosterone and dihydrotestosterone). Secondary outcome measures included 6-month changes in prostate-related clinical features, histology, biomarkers, and epithelial cell gene expression. RESULTS: Of the 44 men randomized, 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per-protocol analysis (TRT, n = 21; placebo, n = 19). Testosterone replacement therapy increased serum testosterone levels to the mid-normal range (median at baseline, 282 ng/dL [9.8 nmol/L]; median at 6 months, 640 ng/dL [22.2 nmol/L]) with no significant change in serum testosterone levels in matched, placebo-treated men. However, median prostate tissue levels of testosterone (0.91 ng/g) and dihydrotestosterone (6.79 ng/g) did not change significantly in the TRT group. No treatment-related change was observed in prostate histology, tissue biomarkers (androgen receptor, Ki-67, CD34), gene expression (including AR, PSA, PAP2A, VEGF, NXK3, CLU [Clusterin]), or cancer incidence or severity. Treatment-related changes in prostate volume, serum prostate-specific antigen, voiding symptoms, and urinary flow were minor. CONCLUSIONS: These preliminary data suggest that in aging men with late-onset hypogonadism, 6 months of TRT normalizes serum androgen levels but appears to have little effect on prostate tissue androgen levels and cellular functions. Establishment of prostate safety for large populations of older men undergoing longer duration of TRT requires further study. Trial Registration clinicaltrials.gov Identifier: NCT00161304.

Adult↗
PubMed2006

APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer.

BACKGROUND: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer diagnostic tool. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine. METHODS: Whole-urine specimens were collected after digital rectal examination from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (<45 years of age with no known prostate cancer risk factors; n = 52), and men who had undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400 Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio, and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA yield were also evaluated. RESULTS: The specimen informative rate (fraction of specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical research study, ROC curve analysis of prebiopsy specimens yielded an area under the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in postprostatectomy specimens except for one man with recurrent prostate cancer. Assay interrun CVs were < or =12%. Both mRNAs were stable in processed urine up to 5 days at 4 degrees C and after 5 freeze-thaw cycles. CONCLUSION: The APTIMA PCA3 assay combines simple specimen processing with precise assays and existing instruments and could add specificity to the current algorithm for prostate cancer diagnosis.

Aged↗
PubMed2006

Relationship among serum testosterone, sexual function, and response to treatment in men receiving dutasteride for benign prostatic hyperplasia.

CONTEXT: Although benign prostatic hyperplasia (BPH) is an androgen-dependent disorder, little is known regarding the influence of serum testosterone levels on sexual or prostate function or clinical response to dutasteride. OBJECTIVE: The objective of the study was to explore these relationships in a large cohort of men treated with dutasteride for BPH. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: Among 4254 men with BPH participating in 2-yr placebo-controlled dutasteride trials, 27% had a pretreatment serum testosterone less than 300 ng/dl. These 1162 men were divided into seven groups based on their serum testosterone level (<150, 150-174, 175-199, 200-224, 225-249, 250-274, and 275-299 ng/dl) and compared with men with normal baseline serum testosterone (BST; > or = 300 ng/dl). Questionnaires were used to assess sexual function, prostate-specific antigen (PSA), and prostate volume to assess androgenic stimulation of the prostate and the American Urological Association Symptom Index to assess clinical responses. RESULTS: Although lower BST was associated with increased sexual dysfunction, this increase was not seen until BST was less than 225 ng/dl. There was no decrease in baseline PSA and prostate volume at low BST levels. Dutasteride was effective at decreasing PSA and prostate volume and improving BPH symptoms at all BST levels. CONCLUSIONS: In men with BPH, the frequency of sexual dysfunction increases at serum testosterone concentrations less than 225 ng/dl. However, PSA and prostate volume were similar at all testosterone levels, explaining why BPH can occur in men that would otherwise be considered hypogonadal. The fact that dutasteride is also effective in men with normal and low testosterone levels suggests that the high levels of 5alpha-reductase and dihydrotestosterone in the prostate allow the development and progression of prostatic hyperplasia, even at low circulating testosterone levels.

Aged↗
PubMed2006

Use of 5alpha-reductase inhibitors to prevent benign prostatic hyperplasia disease.

A histologic change in the prostate, benign prostatic hyperplasia (BPH), is a normal part of aging. However, BPH disease, defined here as a life-altering urinary condition caused by BPH requiring prompt medical intervention, is a serious medical disorder associated with major complications, surgical intervention, and severe lifestyle interference. BPH disease is preventable. The rationale for BPH disease prevention rests on four pillars of evidence: (1) BPH disease generally is a progressive disorder; (2) complications and severe lifestyle interference from BPH disease are common and serious; (3) men at greatest risk of BPH disease can be identified using prostate-specific antigen (PSA) level higher than 1.5 ng/mL as a surrogate marker for an enlarged prostate; and (4) 5alpha-reductase inhibitors (5ARIs) reduce the primary androgen responsible for prostate growth (dihydrotestosterone), shrink the prostate, and arrest the disease process regardless of symptom status. Thus, we now can identify men with an enlarged prostate at risk for BPH disease who may be candidates for preventive therapy with 5ARIs, regardless of urinary symptoms or bother.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2006

The interpretation of serum prostate specific antigen in men receiving 5alpha-reductase inhibitors: a review and clinical recommendations.

PURPOSE: We reviewed the effects of 5alpha-reductase inhibitors on prostate specific antigen and clarified the adjustments that should be made to compensate for these effects to ensure that the usefulness of prostate specific antigen for detecting prostate cancer is maintained. MATERIALS AND METHODS: We reviewed articles published in the scientific literature with relevance to the effects of 5alpha-reductase inhibitors on the usefulness of prostate specific antigen for detecting prostate cancer. RESULTS: A total serum prostate specific antigen of 4.0 ng/ml has traditionally been used as the threshold for triggering prostate biopsy. However, clinical trials of finasteride and dutasteride have shown that 5alpha-reductase inhibitors decrease serum prostate specific antigen in patients with and without prostate cancer. To compensate, the doubling rule has been applied in clinical trials and clinical practice. However, doubling serum prostate specific antigen may overestimate actual prostate specific antigen in some patients receiving 5alpha-reductase inhibitors for up to 6 to 9 months, accurately estimate prostate specific antigen from 1 to 3 years and underestimate it thereafter. An increase in prostate specific antigen of 0.3 ng/ml from nadir as a trigger for biopsy maintains 71% sensitivity for prostate cancer in men receiving dutasteride with 60% specificity, similar to the 4.0 ng/ml prostate specific antigen cutoff using placebo. CONCLUSIONS: We propose that a prostate specific antigen increase from nadir of 0.3 ng/ml or greater could represent an alternative to the doubling rule for monitoring prostate specific antigen in patients on 5alpha-reductase inhibitors. The prostate specific antigen increase from nadir appears to be a more accurate cancer indicator than a doubled value in some patients.

Cholestenone 5 alpha-Reductase↗
PubMed2006

Prevention of benign prostatic hyperplasia disease.

PURPOSE: We reviewed the evidence that benign prostatic hyperplasia is a progressive condition and men at risk for benign prostatic hyperplasia disease can be identified, treated and protected to a meaningful extent regardless of symptom status. MATERIALS AND METHODS: The MEDLINE database was searched in 4 areas of interest relating to benign prostatic hyperplasia, including 1) progression of clinical manifestations with age, especially in regard to baseline symptom status, 2) the incidence of complications due to disease progression, 3) the use of predictive factors that may help identify men at risk for disease progression and 4) the prevention of benign prostatic hyperplasia disease with medical therapy. RESULTS: Tissue changes in the prostate (benign prostatic hyperplasia) are inevitable consequences of aging. However, benign prostatic hyperplasia disease, which we define as a life altering urinary condition requiring medical intervention, is predictable and preventable. Benign prostatic hyperplasia disease progression is associated with increasing prostate volume, decreasing urinary flow, symptomatic deterioration often to the point of major life-style interference and serious complications, eg acute urinary retention and the need for surgery. The risk of benign prostatic hyperplasia disease progression was found to be directly related to prostate volume and its surrogate marker, serum prostate specific antigen, after prostate cancer is excluded. Other factors, eg baseline symptoms and the flow rate, were found to be less relevant compared with prostate specific antigen greater than 1.5 ng/ml for predicting benign prostatic hyperplasia disease morbidity. CONCLUSIONS: Men at risk for benign prostatic hyperplasia disease can be identified using prostate specific antigen greater than 1.5 ng/ml as a surrogate marker of prostate volume. In men at risk with prostate specific antigen greater than 1.5 ng/ml 5alpha-reductase inhibitors have potential value for benign prostatic hyperplasia disease prevention regardless of symptom status.

Adult↗
PubMed2006

Prostatic tissue testosterone and dihydrotestosterone in African-American and white men.

OBJECTIVES: To compare tissue androgen levels in the prostate gland of African-American and white men, looking for a possible explanation of the increased incidence of cancer in the former. METHODS: The subjects were 25 African-American and 36 white men, undergoing prostate biopsy consecutively, in whom cancer was absent. Biopsy cores (18 gauge) from the peripheral zone were homogenized, subjected to ether extraction, and separation by chromatography. Tissue testosterone and dihydrotestosterone (DHT) levels were determined by radioimmunoassay. RESULTS: The groups were matched for mean age (67.6 +/- 9.6 years), prostate volume (37.9 +/- 21.0 cm3), body mass index (28.2 +/- 4.2 kg/m2), and serum prostate-specific antigen (2.8 to 3.4 ng/mL) and testosterone (330 +/- 114 ng/dL) levels (P = NS for all measures). No significant difference in tissue testosterone (median 0.8 ng/g) or DHT (median 4.6 ng/g) was found between groups (P = NS). Furthermore, the tissue DHT/testosterone ratio (approximately 5) was not significantly different between the two groups (P = NS). CONCLUSIONS: Prostatic tissue levels of testosterone and DHT were similar in African-American and white men; thus, the present data do not support a hypothesis of increased androgenic activity in African-American men. Because the ratio of DHT/testosterone in prostatic tissue was similar in the two groups, the possibility of increased 5-alpha-reductase activity in African-American men did not seem likely. Using needle biopsy specimens, both absolute values and the ratio of the androgens in prostatic tissue were similar to those found in previous studies using surgically excised glands. Thus, quick-frozen biopsy cores appear to be a valuable tissue source for evaluating the androgen status within the prostate.

Adult↗
PubMed2006

Alterations in nuclear structure and expression of proPSA predict differences between native Japanese and Japanese-American prostate cancer.

OBJECTIVES: To differentiate the benign and/or malignant epithelial cells in prostate cancer (PCa) glands of native Japanese (NJ) and Japanese-American (JA) men using biomarkers. METHODS: Tissue microarrays from radical prostatectomy specimens of cancerous and adjacent benign areas from 25 NJ and 25 JA prostate glands were studied. Image analysis was used to quantify total prostate-specific antigen (PSA) and proPSA immunohistochemical staining, as well as the variance of several morphometric features from Feulgen-stained epithelial cell nuclei. Logistic regression analysis was applied to determine whether quantitative nuclear grade (QNG) calculations and PSA immunohistochemical staining could differentiate the two test groups. RESULTS: The QNG model differentiated changes in the benign epithelium of the two Japanese groups with an area under the receiver operating characteristic curve of 84% and accuracy of 82% (P = 0.0001). A second QNG model differentiated changes in the malignant epithelium of the two groups with an area under the receiver operating characteristic curve of 84% and accuracy of 76% (P = 0.0023). Logistic regression models combining proPSA immunohistochemical data and QNG from either benign or malignant tissue components yielded areas under the receiver operating characteristic curve of 96% and 91% (P <0.0001) for differentiation of the JA and NJ groups, respectively. CONCLUSIONS: Unique nuclear morphometric alterations demonstrated by QNG combined with proPSA immunohistologic localization independently predicted for significant differences between NJ and JA men with PCa. These preliminary observations indicate a basis for biologic and molecular alterations in the benign adjacent and malignant epithelium between these two groups.

Asian↗
PubMed2004

Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia.

OBJECTIVES: To assess the long-term safety and efficacy of dutasteride, a dual type 1 and type 2 5-alpha-reductase inhibitor, in the treatment of symptomatic benign prostatic hyperplasia and associated lower urinary tract symptoms. METHODS: Data from two Phase IIIa multicenter, randomized, placebo-controlled trials of 2-year duration plus a 2-year open-label extension were pooled and analyzed. The entry criteria included age 50 years old or older, clinical diagnosis of benign prostatic hyperplasia, prostate volume of 30 cm3 or greater, American Urological Association symptom score of 12 or greater, peak urinary flow rate of 15 mL/s or less, and prostate-specific antigen level of 1.5 ng/mL or greater but less than 10 ng/mL. RESULTS: A total of 2802 men were randomized into the double-blind phase of the two studies with 1908 patients (68%) completing the study. Of these, 1570 subjects were enrolled in the open-label phase, and 569 subjects received dutasteride for 48 months. Changes at the 48-month visit for dutasteride/dutasteride-treated subjects included improvement in prostate volume (-26.2%), American Urological Association Symptom Index (-6.1 points), and peak urinary flow rate (+2.8 mL/s). Changes for the placebo/dutasteride group included prostate volume (-20.7%), American Urological Association Symptom Index (-5.3 points), and peak urinary flow rate (+1.8 mL/s). Acute urinary retention and surgery occurred in a small percentage of subjects (less than 2% and less than 1%) in the open-label extension phase. Dutasteride was well tolerated with no statistically significant increase in drug-related adverse events during the open-label extension and no adverse laboratory trends. CONCLUSIONS: Dual inhibition of 5-alpha-reductase with dutasteride provided sustained efficacy in subjects with symptomatic benign prostatic hyperplasia treated for 48 months. Near-complete, long-term suppression of dihydrotestosterone (93% at 48 months) with dutasteride did not lead to an increase in adverse events compared with that reported in the 2-year period.

5-alpha Reductase Inhibitors↗
PubMed2004

Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.

OBJECTIVES: To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues. METHODS: The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. RESULTS: The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. CONCLUSIONS: NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence CaP evolution. The CaP specimens from the NJ and J-A men were histologically similar, but tissue biomarker expression, especially of lipoxygenase and the caspase family, suggested differing mechanisms of carcinogenesis. Differences in nuclear morphometry suggested the additional possibility of gene-nutrient interactions.

Adenocarcinoma↗
PubMed2004

5alpha-reductase: history and clinical importance.

The treatment of men with symptomatic benign prostatic hyperplasia (BPH) has shifted dramatically from surgery to drug therapy over the past decade. The revolution in BPH treatment began with the discovery of congenital 5alpha-reductase (5AR) deficiency, leading to the appreciation of 2 different androgenic hormones: testosterone, which mediates overt masculinization in the adult male, and dihydrotestosterone (DHT), which mediates prostatic growth, acne, facial beard, and male pattern baldness. Inhibition of DHT in adults results in prostatic shrinkage and symptomatic relief in many men, without the side effects seen with conventional androgen-deprivation therapy. The 5AR inhibitor drugs (finasteride and the dual inhibitor, dutasteride) are able to ablate the accumulation of intraprostatic DHT, the mechanism most responsible for prostate growth and maintenance. Not only may these drugs relieve symptoms, but they may also alter the natural history of the BPH process. Future indications for the 5ARI drugs could include chemoprevention of prostate cancer, prophylaxis of BPH-related complications, and treatment of BPH-associated hematuria.

Journal Article↗
PubMed2003

Luteinizing hormone-releasing hormone agonists in the treatment of men with prostate cancer: timing, alternatives, and the 1-year implant.

This article reviews the evidence underlying hormone treatment decisions for men with advanced prostate cancer. Luteinizing hormone-releasing hormone (LHRH) analogs are the mainstays of therapy, but 3 areas of LHRH use need clarification: (1) when to start therapy, (2) what alternatives are available, and (3) how to incorporate a long-term strategy for the individual patient. The Medical Research Council (MRC) study, a randomized clinical trial in 938 patients, shows that immediate hormone therapy in men presenting with advanced prostate cancer (stage > or =T3) imparts a survival advantage over a delayed-treatment approach (7.5 years vs 5.8 years, P = 0.0003). LHRH analogs are also widely used (1) along with definitive radiation therapy, (2) when positive lymph nodes are found after radical prostatectomy, and (3) when prostate-specific antigen increases after any primary treatment (biochemical failure). In these situations, timing of therapy is somewhat controversial. Several new developments in hormone therapy are noteworthy, including high-dose antiandrogen monotherapy, a LHRH antagonist (abarelix), transdermal estrogens, and a subcutaneous implant that releases leuprolide acetate at a constant rate for 1 year (Viadur; Bayer Corporation, West Haven, CT). With 4 years of clinical experience with Viadur now available, the long-term data indicate continued, uniform testosterone suppression into the castrate range and a high degree of patient satisfaction. Thus, a long-term strategy-permitting increased patient freedom and decreased dependence on a fixed injection schedule-has for the first time become possible with the Viadur implant in men requiring hormone therapy for prostate cancer.

Androgen Antagonists↗
PubMed2003

First dose efficacy of alfuzosin once daily in men with symptomatic benign prostatic hyperplasia.

OBJECTIVES: To evaluate the onset of action of alfuzosin once daily (OD) as determined by uroflowmetry early after initial dosing. Alfuzosin OD is an extended-release formulation of a uroselective, alpha1-adrenoreceptor-blocking agent (alpha-blocker) used in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: This was a randomized, placebo-controlled, two-way Latin square crossover study. Forty-nine patients were selected for this study on the basis of their symptomatic improvement during previous treatment with alpha-blockers and significant decreases in urinary flow rate when that treatment was withdrawn. RESULTS: Our analysis showed that significant increases in the maximal urinary flow rate (Qmax) in 34 assessable patients occurred as soon as 8 hours after the initial dose of medication and persisted for at least 4 days. The DeltaQmax for alfuzosin 10 mg OD was 3.2 mL/s and for placebo it was 1.1 mL/s. The difference of means for the assessable population was 2.1 (95% confidence interval 0.8 to 3.4, P = 0.002). The overall incidence of adverse events was low. Only dizziness, experienced by 3 patients treated with alfuzosin compared with 1 patient treated with placebo, appeared to be related to the study drug. CONCLUSIONS: Together, our findings suggest that alfuzosin OD exhibits a urodynamically measurable effect on bladder outlet obstruction due to benign prostatic hyperplasia in men with lower urinary tract symptoms within hours of the first administration.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2003

Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease.

BACKGROUND: BPSA is a "benign" form of free prostate-specific antigen (PSA) that is increased in prostate transition zone tissues of men with pathologic benign prostatic hyperplasia (BPH). We developed an immunoassay to determine the concentration of BPSA in the serum of men with BPH. METHODS: The BPSA antigen was purified by HPLC, and murine monoclonal antibodies were prepared by standard methods. A fluorogenic ELISA was developed with high specificity for BPSA and no cross-reactivity with other forms of PSA. RESULTS: The BPSA immunoassay had a lower limit of detection of 6 ng/L and a cross-reactivity of <1% with all other clipped and nonclipped forms of PSA. The BPSA antibody was specific for the internal Lys(182) cleavage site that characterizes BPSA. Biopsy-negative men with a median total PSA of 4.8 micro g/L had a median of 0.22 micro g/L BPSA, representing 25% of the free PSA in serum. BPSA ranged from 0% to 60% of the free PSA in serum. BPSA in a cohort of cancer serum also comprised 25% of the free PSA. Control serum from women or men without increased PSA had nondetectable BPSA. CONCLUSIONS: BPSA is a significant percentage of the free PSA in BPH serum but not in control serum. The presence of prostate cancer does not alter the relative proportions of BPSA in sera with <10 micro g/L PSA. BPSA has a wide distribution of concentrations in the serum and may provide clinical information for the study of men with BPH.

Adult↗