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Role of transurethral biopsy sampling of the prostate to diagnose prostate cancer in men undergoing surgical intervention for benign prostatic hyperplasia.

PURPOSE: Newer minimally invasive surgical procedures are being used to treat men with significant benign prostatic hyperplasia (BPH). These modalities do not allow retrieval of prostate tissue for histologic review. The goal of our study was to assess the value of transurethral biopsies in detecting prostate cancer in men who would undergo surgical intervention for BPH. MATERIALS AND METHODS: Between September 1997 and January 1999, 422 men undergoing transurethral resection of the prostate (TURP) had transurethral biopsies obtained before completing the TURP. Pathology reports as well as prostate-specific antigen (PSA) results were reviewed and analyzed to determine when cancer was present. RESULTS: Pathological examination revealed that cancer was found in 53 men (12.5%). The transurethral biopsies detected cancer in 32 of 53 (60.4%). No cancers were found in the transurethral biopsy specimen only. Of the 21 cancers missed by transurethral biopsy, 7 were stage T1b. PSA level >10 ng/mL increased the likelihood of finding cancer. CONCLUSIONS: Transurethral biopsy sampling is unreliable for detecting prostate cancer in men with clinically significant BPH. Significant cancers are missed if transurethral biopsies are used to determine the presence of carcinoma before minimally invasive surgical therapy for BPH.

Adult↗

[Prostatic cancer developing after transurethral resection of the prostate for benign prostatic hyperplasia].

From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.

Aged↗

[The correlation between the level of prostate-specific antigen and prostate gland volume in the early diagnosis of prostatic cancer].

One hundred and eighty six patients (Pts) presenting with either an abnormal per rectum examination (P.R. suggestive of prostatic cancer (P.Ca) (excluding stage T3) or a prostatic specific antigen (P.S.A.) level greater than or equal to 2.5 ng/ml (radioimmunoassay) were submitted to transrectal ultrasonography (T.R.U.) using a 7 MHz transducer. The prostatic volume (Vol.P) was systematically calculated during T.R.U. and correlated with the P.S.A. level. Six systematic multiple ultrasound-guided biopsies (S.M.U.B.) were performed in the 2 prostatic lobes (3 per lobe) regardless of the result of T.R.U. In the 111 patients in whom the S.M.U.B. were negative, a highly significant correlation (p < 0.001) was observed between the serum P.S.A. level (y) and the prostatic volume (Vol.P): y = (4.13 +/- 0.15 Vol.P) +/- 8.43. In the 75 Pts with P.Ca, the P.S.A./Vol.P correlation was significantly different (p < 0.05) from the straight line of regression with the previous standard deviation. A similar difference in correlation (p < 0.05) was observed in the sub-group of 14 Pts with P.Ca despite normal P.R. and T.R.U. These results suggest: 1) that there is a correlation between the Vol.P measured by T.R.U. and the P.S.A. level in patients with negative S.M.U.B. 2) that the absence of correlation is highly suspicious of P.Ca and requires S.M.U.B. 3) that there is a 15% incidence of P.Ca in the sub-group of Pts with normal P.R. and T.R.U. which are only detected by the raised P.S.A. not correlated with the volume of the prostate.

Biopsy↗

Expression and regulation of metallothionein mRNA levels in the prostates of noble rats: lack of expression in the ventral prostate and regulation by sex hormones in the dorsolateral prostate.

The rat prostate is composed of two anatomically well-defined regions designated as the ventral prostate (VP) and the dorsolateral prostate (DLP). VP and DLP are known to exhibit marked cytological, biochemical, and functional differences including differential susceptibilities to carcinogens. While the VP is uniquely susceptible to cadmium carcinogenicity [1,2], the DLP is sensitive to sex hormone-induced cancer [3,4]. The role played by the heavy metal binding protein, metallothionein (MT), in the prostate is largely unknown. It is still controversial as to whether MT is expressed in the rat gland. The aim of the present study is to examine the expression pattern of MT mRNA in the rat gland and its probable regulation by heavy metal ions and sex hormones, in order to gain insight into the biological function of MT in the prostate. Northern hybridization and reverse transcriptase-polymerase chain reaction analyses revealed constitutive expression of MT mRNA in the DLP and a lack of expression of the transcript in the VP. In situ hybridization localized the transcript to the epithelium of the DLP, with the lateral prostate epithelium exhibiting the highest level of expression. Administration of cadmium and zinc failed to induce MT transcription in the VP, nor were these treatments effective in elevating levels of MT mRNA in the DLP. A 60% reduction in MT message levels was observed in the DLP following orchiectomy. MT transcript levels in the DLPs of castrates were restored by readministration of androgen to the animals. Long-term treatments (16 weeks) of rats with estradiol-17 beta (E2) or testosterone (T) plus E2 induced a 2.8-fold and a 5-fold increase in MT message content in the DLP, respectively. In sum, MT mRNA was shown to be absent in the VP and was not inducible by heavy metal ions or hormones in this prostatic lobe. These findings substantiate the belief that MT plays a role in heavy metal detoxification and deficiency in its expression may contribute to the unique susceptibility of the VP to cadmium carcinogenicity. By contrast, constitutive expression of MT was demonstrated in the DLP, which was shown to be regulated by androgen and not by exogenously administered heavy metal ions. These results suggest a participatory role of MT in the normal functioning of the DLP. The fact that high levels of MT mRNA were induced in the DLP following long-term estrogenic or conjoint androgenic-estrogenic action alludes to the possibility that MT may serve as an intracellular antioxidant in DLP cells.

Androgens↗

Three-dimensional computer-simulated prostate models: lateral prostate biopsies increase the detection rate of prostate cancer.

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. METHODS: We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. RESULTS: The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-region biopsy protocol had a 90.5% detection rate and the 14-pattern, which includes all the biopsies used in the patterns above, only added 1 additional positive case (99.5%). Transitional zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. Only one positive model was obtained when the transitional zone biopsies were added. The lateral sextant pattern had a detection rate of 95.5%, and the 4-pattern lateral biopsy protocol had a 93.5% detection rate. CONCLUSIONS: Our results suggest that all the biopsy protocols that use laterally placed biopsies based on the 5-region anatomic model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.

Biopsy, Needle↗

Impact of prostate size on the outcome of transurethral laser evaporation of the prostate for benign prostatic hyperplasia.

OBJECTIVES: The aim of this study was to evaluate efficacy and safety of transurethral evaporation of the prostate (TUEP) using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in prostate glands of various sizes. METHODS: One hundred consecutive patients with benign prostatic hyperplasia (BPH) and prostate volumes less than 40 cc (group I, n = 41), 41 to 80 cc (group II, n = 39), and more than 80 cc (group III, n = 20), who had preoperative prostate volume estimation by transrectal ultrasound and had completed a minimum of 3 months' follow-up, underwent TUEP. At baseline, and at 3 and 6 months, American Urological Association (AUA) score, peak flow rate (PFR), postvoid residual urine (PVR), and complications, if any, were documented. RESULTS: There were no significant differences in failure rates, complications, or ability to improve symptom score, PFR, and PVR between patients with prostate glands of various sizes. The mean improvement in PFR at 6 months was: group I, 9.9 cc/s (116%); group II, 7.4 cc/s (81%); and group III, 9.2 cc/s (107%). Reduction in AUA score was: group I, 14.6 (63%); group II, 17.7 (71%); and group III, 16.2 (70%). PVR was: group I, 62.5 cc (51%); group II, 31.4 cc (16%), and group III, 71 cc (83%) (differences not significant). The patients in urinary retention were separately analyzed (group I, 9, group II, 12, and group III, 5) and mean PFR at 6 months was: group I, 18.5 cc/s, group II, 15 cc/s, and group III, 17.1 cc/s. Mean AUA score at 6 months was: group I, 25.8; group II, 21; and group III, 23.6. Mean PVR score was: group I, 370 cc, group II, 439 cc; and group III, 400 cc (differences not significant). Mean postoperative catheterization time was higher in patients with glands larger than 80 cc (2.2 versus 2.9 versus 4.7 days in groups I, II, and III, respectively, P < 0.009 between groups II and III). Incidence of urinary tract infection (10 versus 0%) was greater in patients receiving only 48-hour as opposed to 10-day postoperative antibiotics. CONCLUSIONS: TUEP appears to be a safe and effective treatment for relief of symptoms of BPH and improvement of PFR in patients with all sizes of prostate glands.

Aged↗

Epidemiology of radical prostatectomy for localized prostate cancer in the era of prostate-specific antigen: an overview of the Department of Defense Center for Prostate Disease Research national database.

BACKGROUND: Because of public awareness and screening, the incidence of clinically localized prostate cancer has increased dramatically in the last 15 years. The Department of Defense Center for Prostate Disease Research (CPDR) was established by the US Congress in 1991 to study prostate cancer in the US military health care system. A key component of CPDR is a multicenter prospective and retrospective prostate research database that collects comprehensive standardized data on all consenting patients. To verify and document changes in the epidemiology of men electing radical prostatectomy (RP) as primary treatment for their localized prostate cancer, we undertook an analysis of such cases when the PSA screening test became widely available and used. METHODS: The CPDR database consists of standardized data collection forms for each episode of care completed prospectively, and in some cases, retrospectively, on men with prostate cancer and those undergoing a prostate biopsy for presumed cancer at participating medical centers. In July 2001, a query of all RPs performed between January 1, 1991, and December 31, 2000, was conducted, revealing 3681 cases for analysis from 9 hospital sites. These cases were analyzed over time (calendar year), and changes in the characteristics of the patients, disease severity, and surgical results were compared. RESULTS: There was a significant shift to younger men undergoing RP with the median age declining to 62.3 years old by 2000, and more than 40% of the men were less than 60 years old. There was an increase in African-Americans undergoing RP and a large increase in clinical stage T1 disease candidates of both races representing 56.5% of men by 2000. There was a large increase in patients having pretreatment PSA levels between 4 and 10 ng/mL (59.2% by 2000). Retropubic approach was predominant (over 80%) and was associated with a much lower blood loss by 2000 (approximately 800 mL). There was an increase in use of nerve-sparing procedures, and operative time declined significantly to a median of 3.5 hours by 2000. Finally, there was a marked surgical stage migration with a higher proportion of men with organ-confined disease and negative surgical margins; by 2000, 63.4% had pT2 disease. The early outcomes improved with a 1-year disease-free survival in excess of 93%. CONCLUSIONS: RP is being performed more commonly on younger men with earlier stage disease in the PSA era. The operation is now performed more rapidly with less blood loss, and the surgical pathology outcome end points and early disease-free survival are improved. These results portend well for improved long-term outcomes of surgical therapy.

Age Distribution↗

Combined analysis of hereditary prostate cancer linkage to 1q24-25: results from 772 hereditary prostate cancer families from the International Consortium for Prostate Cancer Genetics.

A previous linkage study provided evidence for a prostate cancer-susceptibility locus at 1q24-25. Subsequent reports in additional collections of families have yielded conflicting results. In addition, evidence for locus heterogeneity has been provided by the identification of other putative hereditary prostate cancer loci on Xq27-28, 1q42-43, and 1p36. The present study describes a combined analysis for six markers in the 1q24-25 region in 772 families affected by hereditary prostate cancer and ascertained by the members of the International Consortium for Prostate Cancer Genetics (ICPCG) from North America, Australia, Finland, Norway, Sweden, and the United Kingdom. Overall, there was some evidence for linkage, with a peak parametric multipoint LOD score assuming heterogeneity (HLOD) of 1.40 (P=.01) at D1S212. The estimated proportion of families (alpha) linked to the locus was.06 (1-LOD support interval.01-.12). This evidence was not observed by a nonparametric approach, presumably because of the extensive heterogeneity. Further parametric analysis revealed a significant effect of the presence of male-to-male disease transmission within the families. In the subset of 491 such families, the peak HLOD was 2.56 (P=.0006) and alpha =.11 (1-LOD support interval.04-.19), compared with HLODs of 0 in the remaining 281 families. Within the families with male-to-male disease transmission, alpha increased with the early mean age at diagnosis (<65 years, alpha =.19, with 1-LOD support interval.06-.34) and the number of affected family members (five or more family members, alpha =.15, with 1-LOD support interval.04-.28). The highest value of alpha was observed for the 48 families that met all three criteria (peak HLOD = 2.25, P=.001, alpha=.29, with 1-LOD support interval.08-.53). These results support the finding of a prostate cancer-susceptibility gene linked to 1q24-25, albeit in a defined subset of prostate cancer families. Although HPC1 accounts for only a small proportion of all families affected by hereditary prostate cancer, it appears to play a more prominent role in the subset of families with several members affected at an early age and with male-to-male disease transmission.

Age of Onset↗

Nuclear factor-kappaB is constitutively activated in prostate cancer in vitro and is overexpressed in prostatic intraepithelial neoplasia and adenocarcinoma of the prostate.

PURPOSE: The transcription factor nuclear factor-kappaB (NF-kappaB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis. EXPERIMENTAL DESIGN: Electromobility gel shift assays were used to evaluate NF-kappaB DNA binding in vitro. The functional relevance of NF-kappaB DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-kappaB inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-kappaB subunit was used to determine the frequency and location of NF-kappaB in 97 prostatectomy specimens. The amount of staining was quantified on a 0-3+ scale. RESULTS: An electromobility gel shift assay confirmed the presence of NFkappaB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-kappaB and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1+ and 2+ with no 3+ staining in benign epithelium, whereas there was only 2+ and 3+ staining (30 and 70%, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage. CONCLUSIONS: NF-kappaB is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-kappaB, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-kappaB for the prevention and/or treatment of prostate cancer.

Adenocarcinoma↗

Active principle of swine prostate extract: I. Isolation of active principle activating prostatic acid phosphatase and its effect on testosterone uptake of the prostate in castrated rats.

There have been several reports concerning the therapeutic effect of an extract from animal prostates on benign prostatic hypertrophy. Previously, we reported that the swine prostate extract (PE) had the activity to enhance human prostatic acid phosphatase (PAPase) activity in vitro, and to increase the muscular tonicity of the urinary bladder by directly acting upon vesical muscles, suggesting that PE have an activity to elevate the intravesical voiding pressure in vivo. In the present study, it was attempted to isolate such an active principle of PE as activates human prostatic acid phosphatase (PAPase). The finally purified PE (PPE) was assessed as to some physico-chemical and pharmacological properties. 1) PPE was found to be a peptide with a molecular weight of about 8,800, composed largely of neutral amino acids (approximately 70%) and few of aromatic amino acids. 2) PPE activated PAPase in a dose-dependent fashion, resulting in an increase of the enzyme activity approximately twice in a dose of 2 X 10(-5) g/ml of PPE. Furthermore, PPE recovered PAPase activity dose-dependently from the 50% inhibition by 2 X 10(-3) M L-tartaric acid. 3) In castrated rats, the 3H-testosterone uptake of the prostate was significantly suppressed by the oral administration of PPE. PPE might be one of active principles of PE for the therapeutic effect on prostatic hypertrophy.

Acid Phosphatase↗

[Clinical studies on chronic prostatitis and prostatitis-like syndrome (4). The kampo treatment for intractable prostatitis].

Kampo treatment was attempted in cases of chronic nonbacterial prostatitis and prostatitis-like syndrome which was intractable or recurred when treated with western medicine. The clinical effects of Kampo treatment were excellent in 21.3% with an efficacy rate of 67.2% for the cases with chronic non-bacterial prostatitis, and excellent in 19.5% with an efficacy rate of 52.4% in the cases with prostatitis-like syndrome. When the clinical effects were compared with those of western therapy performed in the cases which had recurrence, Kampo treatment showed more excellent effects (p less than 0.1) for both types of disease, and the treatment with Chinese medicine was suggested useful. In a comparison of the effects between the cases given only Kampo treatment and those given both Kampo treatment and western treatment using anti-inflammatory agents, no difference was seen in the cases with the prostatitis-like syndrome, but in the cases with chronic non-bacterial prostatitis, the effects were better in the concomitant treatment group than in the group given only Kampo treatment (p less than 0.1). The response to the Kampo treatment differed depending on the type of disease. Among the antibacterial agents used concomitantly in the cases of chronic non-bacterial prostatitis, new-quinolones showed better results than ST compounds or tetracyclines, but no statistically significant differences were seen among the drugs. Of the Kampo drugs used, Keisibukuryogan and Simotuto showed high clinical usefulness in both types of disease and there was no statistically significant difference among the other drugs. The incidence rate of side effects (Goji) due to Kampo treatment was 6.3% and was higher in patients administered Keisibukuryogan.

Adult↗

Transforming growth factor-beta 3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma.

BACKGROUND: We investigated the role of the transforming growth factor beta (TGF-beta) family in the neoplastic progression of the human prostate. METHODS: Expression of TGF-beta mRNA was measured by Northern blot analysis of tissue extracts, and TGF-beta protein by immunohistochemical analysis of tissue sections. Proliferating cells were detected by their expression of Ki-67 antigen. RESULTS: The level of TGF-beta 1 mRNA was equal among normal prostate, benign prostatic hyperplasia (BPH), and prostate carcinoma. TGF-beta 2 mRNA was not detectable, and TGF-beta 3 mRNA was expressed 20-fold lesion in carcinoma compared to BPH and normal prostate. TGF-beta 1 protein was expressed in the stromal cells in all three tissues and TGF-beta 3 protein in the basal layer of epithelial cells, but not in carcinoma. Proliferating epithelial cells fail to express TGF-beta 3. CONCLUSIONS: TGF-beta 1 and TGF-beta 3 are independently regulated, and carcinoma of the prostate is characterized by the loss of basal epithelial cells expressing TGF-beta 3.

Adult↗

Immunoreactivity for prostate-specific antigen and prostatic acid phosphatase in adenocarcinoma of the prostate: relation to progression following radical prostatectomy.

BACKGROUND: Although, in general, immunoperoxidase staining for prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) cannot distinguish between benign and malignant prostatic epithelium, immunoreactivity of these antigens may be helpful in predicting prognosis of prostate cancer. The purpose of this study was to evaluate intensity and extent of immunoperoxidase staining for PSA and PSAP as a prognostic tool in prostate adenocarcinomas. METHODS: We studied radical prostatectomy specimens from 68 patients with the following stages: organ-confined, 34.3%; focal capsular penetration, 38.8%; established capsular penetration, 25.3%; and seminal vesicle invasion, 1.6%. Ninety-one percent of cases were Gleason score 5-7. The mean follow-up for those men without progression was 8.9 years, compared to 3.5 years for those with progression. Progression was defined as an elevated postoperative serum PSA level (> 0.2 ng/ml). Intensity of PSA and PSAP staining was recorded and based on a scale of 0-3 (0, no staining; 1, weak; 2, moderate; 3, intense). Extent was quantitated on a scale of 0-4 (0, 0-5% staining; 1, 6-35%; 2, 36-65%; 3, 65-95%; 4, 95-100%). A score (0-12) was computed by multiplying intensity and extent of the stain in the tumor area. RESULTS AND CONCLUSIONS: Intensity and extent of PSA and PSAP immunoreactivity did not predict progression in adenocarcinomas of the prostate following radical prostatectomy.

Acid Phosphatase↗

Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): association with diagnosis of prostate cancer.

BACKGROUND: Alpha-methylacyl-CoA racemase (AMACR) is strongly expressed in prostate cancer with variable expression in high-grade prostatic intraepithelial neoplasia (HGPIN) and low expression in normal prostate. We examined whether AMACR expression in HGPIN and normal tissue was associated with subsequent diagnosis of cancer or proximity to a cancer focus. METHODS: Needle core biopsies from 45 patients with isolated HGPIN, 12 radical prostatectomy (RP) specimens with prostatic carcinoma and 6 cystoprostatectomies without prostatic carcinoma were immunostained for AMACR. Among patients with HGPIN, 23 (cases) showed cancer on a later biopsy and 22 (controls) had no cancer with at least 3 consecutive negative biopsies. RESULTS: In the biopsy set, the mean AMACR expression per gland in the normal compartment of the cases (0.29) was significantly higher than the controls (0.21) (P = 0.0006). In the RP set, normal glands near a cancer focus had higher mean AMACR expression than those that were distant (P = 0.0006). There was no difference within the HGPIN compartment between cases and controls in the biopsies, or between near and distant glands in the RP set. Mean AMACR staining of normal glands in the cystoprostatectomy specimens was significantly lower than in normal glands in close proximity to a cancer focus. CONCLUSIONS: Higher expression of AMACR in normal glands near a focus of cancer, as well as in the subjects eventually showing cancer, suggests a possible field effect in prostatic carcinogenesis. AMACR expression in normal glands therefore might be a useful predictor for repeat biopsy outcomes or as an intermediate endpoint in chemoprevention studies.

Aged↗

Qualitative analysis of Coomassie-blue-stained proteins from normal prostate, benign prostatic hypertrophy, or adenocarcinoma of the prostate, separated by two-dimensional protein electrophoresis.

Samples from nine normal prostates (N), ten benign hypertrophic prostates (BPH), and eight adenocarcinomas of the prostate (ACP), obtained from the National Prostatic Cancer Project were analyzed by two-dimensional (2D)-protein electrophoresis. Qualitative analysis of Coomassie-blue-stained acidic proteins between pI 3.5 and 6.8 yielded these results: The total number of enumerated proteins was 136 (N), 107 (BPH), and 147 (ACP). Ninety-two denoted proteins were deemed common to the three kinds of samples, three were considered present in N and BPH, 7 in BPH and ACP, and 28 in N and ACP. Thirteen, five, and 20 proteins were detected only in N, BPH, or ACP. These proteins cannot be considered "unique" to their respective samples, since amounts of protein that do not exceed the minimum sensitivity of the dye may be present in the other samples. The similarity in the patterns of proteins from these three types of prostate samples is consistent with the following hypothesis: The distribution of proteins from histologically ambiguous prostate samples will correlate more closely with these protein profiles than with those associated with cancers originating from other organs.

Adenocarcinoma↗

Comparison of subcellular proteins of normal prostate, benign prostatic hypertrophy, and prostatic cancer: presence of BPH-associated nonhistone proteins.

Proteins in the cytosol, postnuclear particulate, and nuclear fractions from seven specimens of normal prostate from bladder cancer patients, 14 specimens of benign hypertrophic prostate (BPH), and three specimens of cancerous prostate were analyzed and compared by SDS-polyacrylamide slab gel electrophoresis. Abundant protein species in the cytosol fractions were 60K (species having a molecular weight of about 60,000) and 42K; their relative contents were about 35% for 60K and about 12% for 42K. In the postnuclear particulate fraction, 42K was the most abundant (about 10% of the total). The contents of these major protein species were similar in specimens of normal and diseased prostates. In addition, there are marked similarities in the electrophoretic patterns for all the protein (24-29 species) in the cytosol and postnuclear particulate fractions of the human prostate, except for four minor species in the cytosol fraction. Of the nuclear proteins, the content of core histones (H2A, H2B, H3, and H4) was fundamentally similar among all the specimens, whereas the content of H1 histone was different from one specimen to another. The most remarkable and significant difference was that the 42K-NHP (nonhistone protein having a molecular weight of about 42,000), 55K-NHP, and 190K-NHP concentrations were significantly higher in BPH than in normal and cancerous prostates.

Chromosomal Proteins, Non-Histone↗

Aromatization of androstenedione to estrogen by benign prostatic hyperplasia, prostate cancer and expressed prostatic secretions.

Human prostatic tissue and expressed prostatic secretions (EPS) from patients with benign prostatic hyperplasia (BPH) and prostate cancer were incubated with (1 beta 3H) androstenedione. The extent of aromatization was determined by measuring the transfer of 3H from the 1 beta position into water. The amount of 3H2O recovered corresponds to the estrogens formed. Tissue from 5 patients with BPH yielded 2.13 (+/- 1.05) pmol/mg protein/h while the EPS from the same patients yielded 727 fmol/mg protein/h. In patients with prostate cancer the mean formation of estrogens was 388 fmol/mg protein/h (+/- 75). 4-hydroxy-androstenedione, an aromatase inhibitor, successfully inhibited aromatization in BPH and prostate cancer 53-98%.

Androstenedione↗

Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia.

PURPOSE: We performed a case-control study in which we tested the ability of a non-invasive assay to detect telomerase activity and to distinguish between prostatic cancer (Pca) and benign prostatic hyperplasia (BPH) on samples of epithelial cells obtained after prostatic massage. METHODS: Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay. We selected 60 patients with histologically proven Pca (30 cases) or BPH (30 cases). Specimens included in this study were from patients who had no suspicious findings on digital rectal examination for cancer, had clinical evidence of lower urinary tract symptoms, had no sonographic signs of Pca at the transrectal ultrasound evaluation, had total PSA values moderately elevated (2.6-15 ng/ml), and had no evidence of other urological cancers. The whole procedure was conducted in double blind between pathologists and molecular biology operators. RESULTS: Telomerase activity was detected in 90% of Pca cases and in 13% of BPH cases. The sensitivity (90%) and specificity (76%) of this method were calculated. The positive predictive value, negative predictive value, and diagnostic efficiency were 87%, 90%, and 88% respectively. CONCLUSION: Our data indicate that telomerase activity detected by TRAP assay on prostate epithelial cells collected by prostate massage can substantially improve the distinction between Pca and BPH conditions. One of the clinical benefits resulting from the use of this new assay would be to refine the biopsy indication and to avoid for several patients without Pca the unnecessary cost and the complications of prostate biopsy.

Aged↗