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PubMed2003

Relationship between age, prostate volume, prostate-specific antigen, symptom score and uroflowmetry in men with lower urinary tract symptoms.

OBJECTIVES: To estimate the relationship between age and the values of different diagnostic tests in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic enlargement (BPE) and to compare prostate growth curves between the normal population sample, healthy men and men with LUTS. MATERIAL AND METHODS: A series of 354 men (mean age 70.2 years; range 45-91 years) with LUTS due to BPE were stratified into seven age groups and reviewed retrospectively. All patients underwent a standard evaluation, involving determination of the International Prostate Symptom Score (IPSS), digital rectal examination, uroflowmetry, determination of the prostate-specific antigen (PSA) level and transrectal ultrasonography. Descriptive statistics were used to describe all the variables and Spearman's correlation test was used to evaluate the relationships between them. RESULTS: The mean prostate volume was 40.1 (+/-23.9) cm(3) and mean PSA concentration 3.9 (+/-4.2) ng/ml. Both values increased progressively from 27.5 ml and 1.5 ng/ml, respectively in the <54 years age group to 48.2 ml and 5.4 ng/ml, respectively in the <80 years age group. However, in the 75-79 years age group there was a decrease in both prostate volume and symptom score; PSA concentration remained unchanged and maximal flow rate increased slightly. A statistically significant but weak correlation was found between prostate volume and age (r = 0.25, p < 0.0001) and between PSA and age (r = 0.28, p < 0.0001). Prostate volume correlated positively with serum PSA (r = 0.54, p < 0.0001). The correlations between maximum flow rate and age, prostate volume, PSA and IPSS were r = -0.21, p < 0.0001; r = -0.18, p < 0.0006; r = -0.29, p < 0.0001; and r = 0.14, p < 0.0098, respectively. CONCLUSIONS: These data confirm that prostate volume and serum PSA concentration are significantly correlated and increase with advanced age. The correlations between uroflowmetry (Qmax) and age, prostate volume, serum PSA and IPSS were also significant. However, there was no relationship between symptoms and objective measures of BPE. The increase in different parameters of the severity of benign prostatic hyperplasia with advanced age is not continuous. The prostate volume alone is not useful in the estimation of disease severity.

Age Factors↗
PubMed2001

Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma.

BACKGROUND: Methylation of regulatory sequences near GSTP1, which encodes the pi class glutathione S-transferase, is the most common epigenetic alteration associated with prostate cancer. We determined whether the quantitation of GSTP1 methylation in histopathologically distinct prostate tissue samples could improve prostate cancer detection. METHODS: We used a fluorogenic real-time methylation-specific polymerase chain reaction (MSP) assay to analyze cytidine methylation in the GSTP1 promoter in prostate tissue samples from 69 patients with early-stage prostatic adenocarcinoma (28 of whom also had prostatic intraepithelial neoplasia lesions) and 31 patients with benign prostatic hyperplasia. The relative level of methylated GSTP1 DNA in each sample was determined as the ratio of MSP-amplified GSTP1 to MYOD1, a reference gene. We also performed a prospective, blinded investigation to quantitate GSTP1 promoter methylation in sextant prostate biopsy specimens from 21 additional patients with elevated serum prostate-specific antigen levels, 11 of whom had histologically identified adenocarcinoma and 10 of whom had no morphologic evidence of adenocarcinoma. All data were analyzed by using nonparametric two-sided statistical tests. RESULTS: The median ratios (and interquartile ranges) of MSP-amplified GSTP1 to MYOD1 in resected benign hyperplastic prostatic tissue, intraepithelial neoplasia, and adenocarcinoma were 0 (range, 0-0.1), 1.4 (range, 0- 45.9), and 250.8 (range, 53.5-697.5), respectively; all of these values were statistically significantly different (P< .001). The median ratios of MSP-amplified GSTP1 to MYOD1 in the prospectively collected sextant biopsy samples were 410.6 for the patients with adenocarcinoma and 0.0 for the patients with no evidence of adenocarcinoma (P< .001). CONCLUSION: Quantitation of GSTP1 methylation accurately discriminates between normal hyperplastic tissue and prostatic carcinoma in small samples of prostate tissue and may augment the standard pathologic/histologic assessment of the prostate.

Adenocarcinoma↗
PubMed2001

Inflammation and glandular proliferation in hyperplastic prostates: association with prostate specific antigen value.

A series of 73 cases of surgically resected prostatic tissue were histologically diagnosed as nodular hyperplasia, of which 10 (13.69%) cases had chronic prostatitis. The mean value of prostate specific antigen in prostatic hyperplasia without chronic prostatitis and prostatic hyperplasia with chronic prostatitis were 6.09 ng/ml and 13.61 ng/ml respectively. A statistically significant difference of prostate specific antigen level between these two groups were noted (P<.05). The degree of glandular proliferation in nodular hyperplasia was subjectively assessed and was recorded as mild, moderate or severe degree of proliferation. The mean value of prostate specific antigen were 3.28 ng/ml in patients with mild proliferation, 7.21 ng/ml in those with moderate proliferation and 14.78 ng/ml in those with severe proliferation. A significant association between prostate specific antigen level and degree of glandular proliferation was found (P<.05). Chronic prostatitis and glandular proliferation are the two important factors contributing to serum prostate specific antigen elevation in hyperplastic prostates.

Adult↗
PubMed1992

Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines.

In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.

Adenocarcinoma↗
PubMed2003

Cooperation between ectopic FGFR1 and depression of FGFR2 in induction of prostatic intraepithelial neoplasia in the mouse prostate.

Disruption of the regulatory communication from the stroma to the epithelium mediated by the FGF7/10-FGFR2 signaling axis in the prostate and expression of ectopic FGFR1 in prostatic epithelial cells often correlate with prostate cancer progression both in human and in experimental animals. Ectopic expression of constitutively active FGFR1 mutant (caFGFR1) at low levels in prostate epithelial cells induces low- to intermediate-grade prostatic intraepithelial neoplasia (PIN) within 6-8 months and high-grade PIN in 20-25 months. Depression of the FGFR2 signaling in the prostate also disturbs homeostasis in the prostate and induces prostate hyperplasia. To study whether PIN lesions induced by the caFGFR1 were expression-level dependent, and whether expression of the caFGFR1 and depression of the FGFR2 signaling in the prostate synergistically disturbed prostate homeostasis, we generated two new strains of ARR2PBi-caFGFR1 transgenic mice, which highly expressed caFGFR1 in prostatic epithelial cells. The mice were crossed with KDNR mice to generate ARR2PBi-caFGFR1/KDNR bigenic mice. The ARR2PBi-caFGFR1 mice developed high-grade PIN within 8 months, which was significantly faster than the mice expressing caFGFR1 at low levels. In addition, depression of the FGFR2 signaling clearly promoted perturbation of cellular homeostasis induced by the caFGFR1. The results demonstrated that the PIN development in caFGFR1 transgenic mice was caFGFR1 dosage-dependent, and indicated that the ectopic FGFR1 and the resident FGFR2 in epithelial cells had opposite impacts on intercompartmental homeostasis in the prostate. The bigenic mice provide a model with cooperative aberrations in the fibroblast growth factor signaling axis for evaluation of tumor-initiating events in prostate tumorigenesis.

Animals↗
PubMed1991

[A mass screening of the prostatic diseases and serum prostate specific antigen].

We examined the values of prostate specific antigen (PSA) with a RIA kit (Pros Check PSA) and an EIA kit (Market F PA), measuring prostate weights of 125 participants in a mass screening of the prostatic diseases. A mild positive correlation (r = 0.467) between values of PSA (RIA) and prostate weights was found in the participants in whom the prostate cancer was not detected. Since serum PSA levels measured by RIA of 45 normal subjects were 1.8 +/- 1.5 ng/ml (Mean +/- S.D), the upper limit of the normal range was set at 6.3 ng/ml. The participants whose PSA levels exceeded this upper normal range and also whose prostate weights were under 30 g were found in 11 of the 122 subjects (9%). On the contrary, the abnormal values (EIA) were found in only two subjects (one, a prostate cancer and the other, a benign prostate hypertrophy). We, further, examined the PSA values (EIA) in 415 subjects in whom the prostate cancer was detected in 5 (1.2%). The abnormal values were found in 8 (4 prostate cancer, 3 benign prostate hypertrophy and one without prostatic disease). As the false positive rate was very low, the use of PSA is recommended in the first screening of the check up program of the prostatic disease.

Aged↗
PubMed1997

Insulin-like growth factor-binding protein-2 in patients with prostate carcinoma and benign prostatic hyperplasia.

OBJECTIVE: Insulin-like growth factor-binding protein (IGFBP)-2 is a major prostatic IGFBP and may be involved in regulating prostate growth. Patients with prostate carcinoma (PC) have elevated serum IGFBP-2 levels which correlate with the specific PC marker, prostate-specific antigen (PSA). The aims of this study were (i) to investigate whether elevated serum IGFBP-2 is unique to PC or also occurs in benign prostatic hyperplasia (BPH), (ii) to examine the relationships among age, PSA and IGFBP-2 levels, and (iii) to examine longitudinal changes in serum IGFBP-2 with PSA in PC. DESIGN AND PATIENTS: Sixteen patients (61-83 years) with inoperable PC attending the Oncology Unit at a tertiary referral hospital were studied. Some serum samples were obtained retrospectively while the majority were collected prospectively over 13 months of treatment. The patients with PC were compared to eight patients (66-73 years) with histologically-proven BPH and seven male control subjects (61-82 years) with no known prostate abnormality. MEASUREMENTS: A new IGFBP-2 RIA was developed. Serum PSA (by EIA), and IGFBP-2, IGFBP-3, IGF-I and IGF-II (by RIA) were measured in all subjects, and serially in patients with PC. RESULTS: Serum IGFBP-2 was significantly higher in PC with high PSA (560 +/- 66 micrograms/l, n = 12) than PC with normal PSA (292 +/- 65 micrograms/l, n = 4, P = 0.02), BPH (364 +/- 61 micrograms/l, P = 0.03) and controls (367 +/- 44 micrograms/l, P = 0.04). Mean IGFBP-2 in BPH was not different from controls. IGFBP-2 and PSA were significantly correlated with age (r = 0.543 and r = 0.433 respectively) and with each other even when the age effect was removed. Serum IGFBP-2 and PSA levels changed concordantly in all seven PC patients who had serial sampling. Serum IGF-II but not IGF-I or IGFB-3 was higher in PC and BPH than controls (PC 332 +/- 23 micrograms/l, BPH 359 +/- 26 micrograms/l vs. controls 241 +/- 37 micrograms/l; P = 0.03 and 0.02 respectively). CONCLUSIONS: Serum IGFBP-2 levels are uniquely elevated in active prostate carcinoma but not. In benign prostatic hyperplasia. In prostate carcinoma, serum IGFBP-2 levels closely parallel those of prostate-specific antigen and probably reflect tumour burden. The relationship between prostatic-specific antigen and IGFBP-2 is partially independent of their individual relationships with age. Although serum IGFBP-2 is less sensitive than prostate-specific antigen in prostate carcinoma it may have adjunctive value in its management.

Aged↗
PubMed1999

Decreased immunoexpression of prostate inhibin peptide in prostatic carcinoma: a study with monoclonal antibody.

Prostate inhibin peptide (PIP) is a follicle-stimulating hormone (FSH) regulating peptide produced by the prostate. The mechanism of its endocrine role in regulating prostate growth is believed to be androgen-independent but FSH-dependent. Previous studies using polyclonal antibody proposed PIP as a prostatic-specific marker in cancer diagnosis. However, the recently available monoclonal antibody has not yet been evaluated. Paraffin sections of 72 prostatectomy specimens for prostate cancer with or without hormonal blockage therapy and 10 nonneoplastic prostate tissues from autopsy were stained by using PIP monoclonal antibody (clone: 4A6A6) with the avidin-biotin complex method. PIP reactivity was semiquantitatively estimated in prostatic carcinoma (PCA), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal tissue in each case when ever present. Statistical analyses were performed accordingly. PIP expression is predominantly cytoplasmic. Urothelium, seminal vesicles, inflamed prostatic glands, basal cells, and squamous metaplasia were negative for PIP. Average percentage of cells expressing PIP was significantly decreased in PIN (40%) and PCA (14%) when compared with BPH (81%) and normal tissue (68%). There was no correlation of tumor PIP level with patient's age, tumor size, Gleason score, tumor stage, or the usage of preoperative hormonal blockage therapy. PIP monoclonal antibody should be used with caution as a prostate-specific marker in surgical pathology. The mechanism for this alteration and the effect of PIP on prostatic tumor growth, particularly in patients under a variety of hormonal therapies, needs further study.

Adult↗
PubMed2004

Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial.

PURPOSE: Chemoprevention may significantly impact the natural history of prostate cancer. The most potent intraprostatic androgen, dihydrotestosterone, has a significant role in the pathophysiology of prostate cancer. It represents a biologically plausible target for chemoprevention through the inhibition of 5alpha-reductase isoenzymes. MATERIALS AND METHODS: The Reduction by Dutasteride of Prostate Cancer Events clinical trial is an international, multicenter, double-blind, placebo controlled chemoprevention study designed to determine if dutasteride 0.5 mg daily decreases the risk of biopsy detectable prostate cancer. A total of 8,000 men will be randomized to receive dutasteride or placebo for 4 years. Eligible men must be 50 to 75 years old, have a serum prostate specific antigen of 2.5 to 10 ng/ml (ages 50 to 60 years) or 3.0 to 10 ng/ml (older than 60 years). Men must have a negative 6 to 12 core biopsy within 6 months prior to enrollment. Repeat biopsies will be taken at 2 and 4 years. The rates of prostate cancer for each treatment group will be compared. Genetic and protein biomarkers of prostate cancer, and the effect of dutasteride on benign prostatic hyperplasia and prostatitis symptomatology and histopathology will also be assessed. RESULTS: Results remain to be determined. CONCLUSIONS: The study will examine the effects of the dual 5alpha-reductase inhibitor dutasteride on the natural history of prostate cancer in men at increased risk for this malignancy. It affords a unique opportunity to examine biomarkers and genetic linkage for prostate cancer, and assess a range of prostate health outcome measures.

5-alpha Reductase Inhibitors↗
PubMed2004

[Systematic prostate biopsy before transurethral resection of the prostate].

PURPOSE: With the aim of evaluating the clinical significance of systematic prostate biopsy before transurethral resection of the prostate (TUR-P), clinical data were reviewed retrospectively in patients who had underwent prostate biopsy prior to scheduled TUR-P. PATIENTS AND METHODS: Between July, 1994 and June, 2000, TUR-P was scheduled in a total number of 456 patients with clinically diagnosed benign prostatic hyperplasia (BPH). RESULTS: In 218 (47.8%) out of 456 cases, prostatic biopsy was conducted prior to TUR-P due to abnormally elevated serum prostate specific antigen (PSA) levels of 4.0 ng/ml or more, revealing only 22 (10.1%) cases of prostatic cancer. Between these 22 cases with biopsy proven prostatic cancer and 189 cases with BPH confirmed both by biopsy and following TUR-P, statistically significant differences were noted in age (p < 0.05), prostate volume (p < 0.0001) and PSA density (p < 0.01). CONCLUSION: Considering the low positive rate of preoperative prostatic biopsy, it might be suggested that a considerable number of biopsy could be avoided in patients with clinically diagnosed BPH. Based on the results obtained from this study, prostatic biopsy might be unnecessary before TUR-P for those with prostate volume greater than 60 ml or PSA density less than 0.15.

Age Factors↗
PubMed2002

[Clinical study on prostatic cancer detected incidentally by transurethral resection of the prostate].

Transurethral resection of the prostate (TUR-P) was performed on 463 consecutive patients with clinically diagnosed benign prostatic hyperplasia (BPH) between April 1994 and June 2000. Pathological examinations of resected prostatic tissues revealed prostatic cancer in 15 (3.2%) of them. Eight (53.3%) of them were in stage A1, and 7 (46.7%) in stage A2. Between 15 cases with prostatic cancer and those with BPH, clinical features including age, serum prostate specific antigen (PSA) levels, prostatic volume, PSA density (PSAD), and resected prostatic tissue weight were compared. As a result, age was the only parameter related with prostatic cancer with a statistically significant difference. The higher the age, prostate cancer was found more frequently. Postoperatively, radical prostatectomy and antiandrogen therapy were performed in 1 and 9 cases, respectively. The remaining 5 cases are being followed with no treatment for prostatic cancer, and have shown no findings suggesting recurrence. These 15 cases are all living disease-free at present. It seems of importance to explain preoperatively the possible detection of prostatic cancer in association with TUR-P, particularly for elderly patients aged 80 years or older.

Adenocarcinoma↗
PubMed2002

Fas and Fas ligand expression is elevated in prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

BACKGROUND: Fas is a Type I membrane receptor of the tumor necrosis factor/nerve growth factor family. On binding to Fas ligand, a Type II transmembrane protein, the Fas/Fas ligand complex, induces apoptosis in target cells. Dysregulation of Fas and Fas ligand expression has been found in some malignant neoplasms. METHODS: Using immunohistochemical analysis, the authors studied the expression of Fas and Fas ligand in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and adjacent benign prostate tissue from 95 radical prostatectomy specimens. RESULTS: The percentage of cells that stained positively with Fas in benign prostate tissue (mean, 2%) was statistically significantly lower compared with that in prostatic intraepithelial neoplasia (mean, 13%; P = 0.0014) and prostatic adenocarcinoma (mean, 31%; P = 0.0001). The staining intensity of Fas was significantly less in benign prostate tissue compared with the staining intensity in PIN and prostatic adenocarcinoma. The percentage of cells that stained positively with Fas ligand in benign prostate tissue (mean, 13%) was statistically significantly lower compared with that in PIN (mean, 47%; P = 0.0001) and in prostatic adenocarcinoma (mean, 53%; P = 0.0001). The staining intensity of Fas ligand was significantly less in benign prostate tissue compared with that in PIN and prostatic adenocarcinoma. CONCLUSIONS: Data from the current study indicate that Fas/Fas ligand is elevated in prostatic malignancy, suggesting that Fas-mediated apoptosis may be a potential target for therapeutic intervention.

Adenocarcinoma↗
PubMed2004

Constitutive and inducible expression of cytochromes P4501A (CYP1A1 and CYP1A2) in normal prostate and prostate cancer cells.

Constitutive and benzo[a]pyrene (B[a]P) inducible expression of CYP1A1 and CYP1A2 in prostate cancer and normal prostate epithelial cells were examined by immunoblotting. Androgen independent prostate cancer cell lines DU145 and PC3 have constitutive expression of CYP1A and CYP1A1 and CYP1A2, respectively. Four micromolar B[a]P did not appear to induce CYP1A1 or CYP1A2 expression in DU145 or PC3 cells. The androgen dependent prostate cancer cell line, LnCap, also has constitutive expression of CYP1A1 and CYP1A2. However, both CYP1A1 and CYP1A2 are induced by treatment of LnCap cells with 4 microM B[a]P. Untreated normal prostate and primary prostate tumor cells have no detectable CYP1A1 expression. Treatment with 4 microM B[a]P induced CYP1A1 expression in both normal and primary tumor prostate cells. Constitutive CYP1A2 expression was detected in normal prostate cells with little or no induction by exposure to 4 microM B[a]P. Primary prostate tumor cells did not show constitutive expression of CYP1A2. However, CYP1A2 was induced by 4 microM B[a]P in primary prostate tumor cells. These observations indicate that hormonal and cancer specific factors affect the expression and induction of the phase I metabolic enzymes, CYP1A1 and CYP1A2 in prostate cells. These observations may be related to the potential smoking-linked higher risk of prostate cancer development and morbidity of prostate cancer patients who smoke.

Benzopyrenes↗
PubMed2005

Image-guided radiotherapy for prostate cancer by CT-linear accelerator combination: prostate movements and dosimetric considerations.

PURPOSE: Multiple studies have indicated that the prostate is not stationary and can move as much as 2 cm. Such prostate movements are problematic for intensity-modulated radiotherapy, with its associated tight margins and dose escalation. Because of these intrinsic daily uncertainties, a relative generous "margin" is necessary to avoid marginal misses. Using the CT-linear accelerator combination in the treatment suite (Primatom, Siemens), we found that the daily intrinsic prostate movements can be easily corrected before each radiotherapy session. Dosimetric calculations were performed to evaluate the amount of discrepancy of dose to the target if no correction was done for prostate movement. METHODS AND MATERIALS: The Primatom consists of a Siemens Somatom CT scanner and a Siemens Primus linear accelerator installed in the same treatment suite and sharing a common table/couch. The patient is scanned by the CT scanner, which is movable on a pair of horizontal rails. During scanning, the couch does not move. The exact location of the prostate, seminal vesicles, and rectum are identified and localized. These positions are then compared with the planned positions. The daily movement of the prostate and rectum were corrected for and a new isocenter derived. The patient was treated immediately using the new isocenter. RESULTS: Of the 108 patients with primary prostate cancer studied, 540 consecutive daily CT scans were performed during the last part of the cone down treatment. Of the 540 scans, 46% required no isocenter adjustments for the AP-PA direction, 54% required a shift of > or =3 mm, 44% required a shift of >5 mm, and 15% required a shift of >10 mm. In the superoinferior direction, 27% required a shift of >3 mm, 25% required a shift of >5 mm, and 4% required a shift of >10 mm. In the right-left direction, 34% required a shift of >3 mm, 24% required a shift of >5 mm, and 5% required a shift of >10 mm. Dosimetric calculations for a typical case of prostate cancer using intensity-modulated radiotherapy with 5-mm margin coverage from the clinical target volume (prostate gland) was performed. With a posterior shift of 10 mm for the prostate, the dose coverage dropped from 95-107% to 71-100% coverage. CONCLUSION: We have described a technique that corrects for the daily prostate motion, allowing for extremely precise prostate cancer treatment. This technique has significant implications for dose escalation and for decreasing rectal complications in the treatment of prostate cancer.

Humans↗
PubMed2001

Establishment of short-term primary human prostate xenografts for the study of prostate biology and cancer.

Human tissue xenograft models are currently the only tool for conducting in vivo analyses of intact human tissue. The goal of the present study was to develop reliable methods for successful generation of short-term primary tissue xenografts from benign and tumor-derived human prostate tissue. Primary human prostate xenografts were established in athymic nu/nu mice from eight of eight benign and five of five prostate cancer tissues, collected from a total of 10 patients who underwent radical prostatectomy for the treatment of prostate cancer. An average of 13 xenografts was established per specimen. Two tissue specimens were cryopreserved for >1 month before successful generation of prostate xenografts. After 1 month in vivo, xenograft tissues were harvested and examined regarding: gross evidence of vascularization; tissue morphology; proliferation; apoptosis; and expression of androgen receptor, prostate-specific antigen, and high molecular weight cytokeratins specific for basal cells in the prostate. Direct comparison of the original tissue specimen and the 1-month xenografts revealed similar histology; similar apoptotic and proliferative fractions in most cases; and comparable expression levels and expression patterns of androgen receptor, prostate-specific antigen, and high molecular weight cytokeratins. These data demonstrate that primary human prostate xenografts, benign and malignant, can be established routinely from human prostate tissue surgical specimens, and that the xenografts maintain tissue architecture and expression of key prostatic markers. The development of this methodology, including the technique for cryopreservation of human tissue, will allow multiple (successive) analyses of human prostate tissue to be conducted throughout time using a tissue sample derived from a single patient; and simultaneous analysis of human prostate tissues derived from a cohort of patients.

Animals↗
PubMed2002

Prostate specific antigen predicts the long-term risk of prostate enlargement: results from the Baltimore Longitudinal Study of Aging.

PURPOSE: Prostate specific antigen (PSA) is a predictor of prostate growth in men with lower urinary tract symptoms. The long-term risk of prostate enlargement as a function of PSA among community dwelling volunteers is unknown. MATERIALS AND METHODS: A Cox proportional hazards regression model was used to study the relationship between baseline PSA level at ages 40 to 49.9 years in 194 men, 50 to 59.9 in 191 and 60 to 69.9 in 144, and prostate enlargement, defined as a prostate volume larger than the 75th percentile for age decade, as measured by magnetic resonance imaging in a longitudinal study of aging (Baltimore Longitudinal Study of Aging, National Institute on Aging). Kaplan-Meier survival analysis was performed to estimate the probability of freedom from prostate enlargement with time as a function of baseline PSA level. RESULTS: The relative risk of prostate enlargement was 3- to 6-fold higher for men 40 to 49.9 years old with a baseline PSA of 0.31 ng./ml. or more compared to men with PSA levels of 0.30 ng./ml. or less at baseline. The relative risk was increased 5- to 9-fold in men 50 to 59.9 years old and 11-fold in those 60 to 69.9 years old when comparing men with PSA greater than 0.80 ng./ml. and greater than 1.70 ng./ml. with those with PSA 0.50 or less. The cumulative probability of freedom from prostate enlargement at 20 years was 0.89 (95% confidence interval ([CI] 0.79-0.99) and 0.63 (0.52-0.74) for men 40 to 49.9 years old with PSA levels below and above 0.30 ng./ml., respectively. For men 50 to 59.9 years old the 10-year probability of freedom from prostate enlargement was 0.90 (95% CI 0.84-0.96) and 0.59 (0.43-0.74) when PSA levels were below and above 0.80 ng./ml., respectively. At age 60 to 69.9 years the 10-year probability of freedom from prostate enlargement was 0.83 (95% CI 0.72-0.93) and 0.27 (0.09 to 0.48) when PSA levels were below and above 1.70 ng./ml., respectively. CONCLUSIONS: These data demonstrate the long-term risk of prostate enlargement by PSA level. Risk stratification based on PSA level may be useful to identify men at greatest risk for adverse events due to prostate enlargement and selection of men for future benign prostatic hyperplasia studies.

Adult↗
PubMed1992

Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia.

There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen for the expression of BMPs one to six in the prostatic tissue of patients with benign prostatic hyperplasia (BPH), non-metastatic prostatic adenocarcinoma and metastatic prostatic adenocarcinoma. BMPs were expressed in both benign and malignant prostate tissue and in the prostate tumour cell lines, PC3 and DU145. BMPs were also expressed in ocular melanoma tissue, a tissue which rarely metastasizes to bone. BMP-6 expression was detected in the prostate tissue of over 50% of patients with clinically defined metastatic prostate adenocarcinoma, but was not detected in non-metastatic or benign prostate samples or in ocular melanoma tissue. These findings suggest that the BMPs may play a role in the osteoinductive activity of prostate metastases and that the pattern of expression of BMPs may be important in the pathogenesis of osteoblastic metastases associated with prostate adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Altered expression of RET proto-oncogene product in prostatic intraepithelial neoplasia and prostate cancer.

BACKGROUND: The RET proto-oncogene encodes a protein that belongs to the tyrosine kinase growth factor receptor family. Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers. We recently identified transcripts of the RET proto-oncogene in human prostate cancer xenografts and prostate cancer cell lines by means of reverse transcription-polymerase chain reaction analyses. The purpose of this study was to investigate Ret protein expression in human prostate tissue. METHODS: Ret protein expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole-prostate sections. The prostate specimens were obtained from 30 patients with prostate cancer after radical prostatectomies. Ret protein expression was compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma tissue associated with an MEN syndrome and papillary thyroid cancer tissue served as positive controls. RESULTS: Ret appeared to be overexpressed in high-grade (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and prostate cancer when compared with its expression level in benign prostatic secretory epithelium. In addition, there was an apparent increase in Ret protein expression with decreased cellular differentiation, i.e., increasing Gleason pattern. CONCLUSION: Expression of the RET proto-oncogene in benign prostatic epithelium, high-grade PIN, and histopathologically advanced prostate cancer suggests that RET may play a role in the growth of both benign and neoplastic prostate epithelial cells.

Drosophila Proteins↗