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PubMed2006

Prevalence of prostate specific antigen testing for prostate cancer in elderly men.

PURPOSE: We investigated the prevalence and outcome of PSA testing for prostate cancer screening or diagnosis in elderly men 75 years or older at our academic medical center. MATERIALS AND METHODS: A cross-sectional study design was used to identify all men 75 years or older who underwent a PSA test through the family medicine or internal medicine service at our institution between January 1, 1998 and June 30, 2004. All patients with a suspected (PSA less than 0.1 ng/ml) or confirmed prior diagnosis of prostate cancer were excluded. The prevalence of PSA testing was then compared to that in younger age groups (45 to 54, 55 to 64 and 65 to 74 years). We then examined the frequency and nature of further evaluation and treatment performed in men following the PSA test. RESULTS: The 8,787 male patients who were 75 years or older generated a total of 82,672 visits in the 5.5-year period. Of these patients 505 (5.7%) underwent at least 1 PSA test. The prevalence of PSA testing in the younger age groups was 10.3% (1,769 of 17,175) in patients 45 to 54 years old, 14.9% (2,052 of 13,772) in those 55 to 64 years old and 11.8% (1,258 of 10,661) in those 65 to 74 years old (chi-square test p <0.001). Of these patients 98 of 343 (28.6%) with PSA between 0.1 and 4 ng/ml were referred to a urologist at our institution and 3 underwent biopsy. None had a prostate cancer diagnosis. Of the 162 patients with PSA more than 4 ng/ml 84 (51.9%) were referred to a urologist. Only 10 of the 84 patients (11.9%) who were referred to a urologist underwent prostate biopsy. Six of the 10 men (60%) were diagnosed with prostate cancer, including 1 with a Gleason 6 tumor, 1 with a Gleason 7 tumor and 4 who were found to have tumors with a Gleason score of 8 or greater. All patients received androgen deprivation therapy, except 1 who received local external beam radiation therapy. An additional patient was diagnosed by biopsy of a vertebral lesion and he received hormone therapy. At a median followup of 51 months (range 28 to 72) 4 of 7 men (57%) were alive with disease. CONCLUSIONS: PSA testing for prostate cancer screening and diagnosis appear to decrease with advancing age. A small but significant proportion of men who are 75 years or older continue to undergo PSA testing. Abnormal PSA results do not always result in further evaluation and therapy for prostate cancer in elderly men. The establishment of firm guideline recommendations regarding PSA testing and further evaluation for prostate cancer in elderly men, perhaps based on individualized geriatric assessment, may be helpful.

Aged↗
PubMed1994

The requirement of the testis in establishing the sensitivity of the canine prostate to develop benign prostatic hyperplasia.

A long-term study on the requirement of the testis in establishing the sensitivity of the canine prostate to develop benign prostatic hyperplasia (BPH) was conducted using 23 aging beagles both with and without their testes. The dogs had received long-term restoration of testosterone and estrogen through silicone implants. When young beagles (0.5 to 1 year of age) were castrated and normal serum testosterone and estrogen levels restored during aging to 5 years, only 50% of these dogs developed BPH in the absence of their testes as opposed to 100% BPH development in intact controls. In addition, two-thirds of the prostates in the treated groups were remarkably reduced in size, being smaller than any prostate observed in the intact controls. If, following castration, the steroid restoration was withheld for 4 years during aging and subsequently administered starting at 5 years of age and continuing for a 6-month period, none of the animals developed complex BPH. Moreover, two-thirds of the prostate glands were reduced in size by more than 60% and were atrophied in spite of the maintenance of normal prostatic tissue dihydrotestosterone levels. Regardless of the time of steroid restoration to a castrate beagle, the periurethral zone of the canine prostate exhibits various degrees of atrophy indicating functional regions within the canine prostate that are sensitive to the requirements of the testes during aging. This study implicates the importance of the testis in increasing the probability and/or sensitivity for the full development of canine BPH.

Aging↗
PubMed1994

Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values.

The objective of this study was to determine the need for repeat prostatic biopsies in men whose initial biopsy results revealed no evidence of cancer or atypia. We evaluated 1,136 men who underwent 1 or more prostatic biopsies in a longitudinal prostate specific antigen (PSA) based prostate cancer screening study that called for biopsy if the serum PSA level was greater than 4.0 ng./ml. (Hybritech assay) and findings on rectal examination or ultrasonography were abnormal or suspicious for cancer. Of the 1,136 men who underwent prostatic biopsy 391 (34%) had prostate cancer on the initial biopsy. Of 427 men who had negative initial biopsy results, a persistent serum PSA level of greater than 4.0 ng./ml. and abnormal rectal or ultrasound examination findings 82 (19%) had cancer on biopsy 2. Of 203 men with persistent abnormalities 16 (8%) had cancer on biopsy 3 and 6 of 91 (7%) had cancer on biopsy 4 or later. Thus, 96% of the cancers were detected through either biopsy 1 or 2. The median initial PSA level, followup PSA levels and the yearly rate of change in PSA were significantly greater in men whose cancer was detected compared with those of men whose cancer was not detected (6.4 versus 5.4 ng./ml., 7.4 versus 6.6 ng./ml. and 1.1 versus 0.7 ng./ml. per year, respectively). There was a trend for a higher percentage of tumors detected through serial screening to be pathologically organ confined with those detected through initial screening (73% versus 62%, p = 0.07). We conclude that men with a persistently elevated serum PSA value after an initial negative prostatic biopsy should routinely undergo at least 1 repeat biopsy to exclude adequately the presence of detectable prostate cancer.

Aged↗
PubMed1992

Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels.

Measurement of serum prostate specific antigen (PSA) is commonly used to evaluate the prostate gland in a variety of clinical settings. We examined the effects of prostatic manipulations, including digital rectal examination, prostate massage, transrectal ultrasonography and transrectal needle biopsy, on serum PSA levels in 199 men. We detected no clinically significant difference between serum PSA levels obtained immediately before and at 5 or 90 minutes after rectal examination in 43 men. We observed falsely increased PSA levels (to greater than 4 ng./ml., Tandem-R) in 1 of 17 men (6%) following prostatic massage and in 3 of 27 men (11%) following ultrasonography. Transrectal needle biopsy caused an immediate increase in serum PSA in 92 of 100 men. In 29 of these 92 men (32%) when followed weekly serum PSA levels did not return to baseline as expected according to the published serum PSA half-life of 2 to 3 days. Biopsies taking 3 or fewer cores (7 patients) resulted in a smaller increase in serum PSA (mean 1.63 +/- 1.12 times the baseline level versus 6.24 +/- 1.10 times baseline, p less than 0.03) and a proportionally shorter duration of PSA elevation (mean 1.43 +/- 0.48 weeks versus 2.13 +/- 0.14 weeks, p = 0.20) than those taking 4 or more cores (93 patients). Prostate size and the presence of cancer had no influence on the duration of PSA elevation following biopsy. We conclude that digital rectal examination, prostatic massage and ultrasonography have minimal effects on serum PSA levels in most patients. However, prostatic needle biopsy usually causes marked elevations of serum PSA levels with a persistent PSA leak into the blood stream lasting longer than expected from the serum half-life of PSA in approximately 25% of the patients.

Antigens, Neoplasm↗
PubMed1992

Screening for prostatic carcinoma with prostate specific antigen.

Prostate specific antigen (PSA), neutral serine protease secreted exclusively by prostatic epithelial cells, has a number of applications in the management of men with prostatic carcinoma. While it is widely recognized that elevated PSA correlates with the presence of carcinoma, little data exist regarding the use of PSA as the initial test in the early detection of prostatic cancer. We measured serum PSA levels in men older than 50 years and performed digital rectal examination and ultrasound guided prostate biopsy of those who had a PSA level of greater than 4.0 ng./ml. A total of 1,249 men entered the protocol, of whom 187 (15.0%) had PSA levels above 4.0 ng./ml. Digital rectal examination and ultrasound guided biopsy were performed at our facility in 105 patients (56.2%). A total of 32 carcinomas (30.5%) was detected, including 23 in men with PSA between 4.1 and 10.0 ng./ml. and 9 in men with a PSA of greater than 10.0 ng./ml. Of the 32 carcinomas 12 (37.5%) occurred in men with normal prostates or glands demonstrating only asymmetry on digital rectal examination, and 3 men had carcinoma despite normal digital rectal examination and no hypoechoic peripheral zone lesion detected on ultrasound. Of the 32 patients 30 had clinically localized carcinoma but 7 of the 16 undergoing radical prostatectomy had pathological upstaging. We conclude that PSA represents an important adjunct to digital rectal examination for the early detection of prostatic carcinoma. The efficacy of this or any other early detection test to decrease prostate cancer mortality necessitates the results of prospectively randomized clinical trials.

Aged↗
PubMed1990

Internal urethrotomy of the prostatic urethra or transurethral resection in benign prostatic hyperplasia.

Transurethral resection of the prostate is the most common technique for the treatment of benign prostatic enlargement. The inconveniences of prostatic resection are retrograde ejaculation and bladder neck stenosis in small prostates. A randomized prospective trial was done to compare the results of conventional transurethral resection of the prostate in 22 patients and urethrotomy of the prostatic urethra in 27 with respect to postoperative retrograde ejaculation, persistent urinary symptomatology and maximal flow rates. After a mean followup of 25 months we concluded that internal urethrotomy of the prostatic urethra is the operation of choice in patients with a prostate of up to 30 gm.

Follow-Up Studies↗
PubMed1975

Prostatic fluid lactic dehydrogenase isoenzyme patterns of prostatic cancer and hyperplasia.

LDH isoenzyme patterns were determined in prostatic fluid from 286 patients with a prostate gland judged to be normal, the site of benign hyperplasia on clinical evidence or the site of benign hyperplasia or carcinoma on the basis of histologic evidence. Fluid from 12 of 15 patients (80 per cent) with carcinoma representing all stages and grades of disease showed an LDH-V/I ratio of more than 3. This ratio was exceeded in only 6 of 57 (11.8 per cent) and 14 of 97 (14.4 per cent) patients in whom the diagnosis of benign prostatic hyperplasia without evidence of infection was established histologically or clinically, respectively. An LDH-V/I ratio exceeding 3 was seen commonly in patients with a diagnosis of benign prostatic hyperplasia with a recent history suggesting infection and more than 10 WBCs per high power field on microscopic examination of the prostatic fluid. These observations suggest that an LDH-V/I ratio exceeding 3 in the prostatic fluid in the absence of a history of infection and more than 10 WBCs per high power field on microscopic examination should be regarded as an indication of a high risk of the presence or development of a malignancy of the prostate. The results obtained also support the concept that, in the presence of malignancy, expressed prostatic fluid provides an adequate sample of cells with altered metabolism.

Adenocarcinoma↗
PubMed1996

Immunolocalization of glycoprotein A-80 in prostatic carcinoma and prostatic intraepithelial neoplasia.

A-80 is a mucin-like glycoprotein associated with exocrine differentiation that shows little or no expression in normal exocrine cells and typical adenomas, but is upregulated in dysplasia and adenocarcinoma of certain organs. Its expression has not been systematically examined in prostatic adenocarcinoma and its putative precursor, prostatic intraepithelial neoplasia (PIN). The authors applied a mouse monoclonal antibody against A-80 in paraffin-embedded sections from 103 cases of prostatic carcinoma, 26 cases of nodular hyperplasia, 7 autopsy samples from normal young adult prostates, and 12 fetal prostates. All but one cancer reacted, although expression was heterogeneous; 75 of 103 stained extensively (> 3+ on a 0 to 5+ scale) and strongly. Staining extent and intensity were independent of tumor grade, and tended to be strong even when focal. Seventy-seven of 84 foci (92%) of high-grade PIN and 38 of 52 foci (73%) of low-grade PIN stained for A-80; reactions were most extensive and intense in high grade PIN. Only 5 of 26 cases (19%) of hyperplasia reacted, and this consisted of weak to moderate staining in sporadic cells; the remainder were negative. Normal adult prostatic epithelium did not express A-80 except for weak and inconsistent staining in foci of inflammation and infarction; atrophic glands were negative. Fetal prostate showed focally strong reactivity. These results indicate that A-80 is selectively expressed in most cases of intraepithelial neoplasia and prostate cancer, but is usually absent in benign and hyperplastic epithelium. The upregulation of glycoprotein A-80 in PIN and adenocarcinoma parallels observations in other organs, such as the breast and colon, suggesting that this is a significant oncodevelopmental molecule with potential clinical applications.

Adult↗
PubMed2002

Improved prostate cancer-specific survival and other disease parameters: impact of prostate-specific antigen testing.

OBJECTIVES: To determine how the implementation of prostate-specific antigen (PSA) testing has affected disease-specific survival and other characteristics of prostate cancer. METHODS: Data were collected on all patients with prostate cancer diagnosed between 1988 and 1998 and registered in the Center for Prostate Disease Research Database at Walter Reed Army Medical Center. Statistical analyses were used to summarize trends over time in survival, mortality, and clinical stage. RESULTS: Between 1988 and 1998, a total of 2042 patients with prostate cancer were registered at Walter Reed Army Medical Center. The 5-year disease-specific survival rate was 86.9% and 93.7% for patients diagnosed in the respective year groups of 1988 to 1991 and 1992 to 1994, with follow-up through December 1, 2000 (P < 0.001). Prostate cancer was the cause of death for 37.5% of the patients in 1988 to 1989 versus 15.4% in 1999 to 2000. Marked stage migration has occurred; from 1988 to 1998, the percentage of patients presenting with metastatic disease decreased from 14.1% to 3.3% (P < 0.001). CONCLUSIONS: A statistically significant improved 5-year disease-specific survival and a decreased chance of dying from prostate cancer has occurred after the widespread implementation of PSA. We suspect that PSA testing has resulted in fewer patients presenting with metastatic disease and more patients presenting with localized disease amenable to curative treatment. This portends well for the use of PSA screening to improve outcomes for prostate cancer. However, randomized trials are needed to confirm the improvements in survival and mortality.

Age Factors↗
PubMed1998

Specific T cell recognition of peptides derived from prostate-specific antigen in patients with prostate cancer.

OBJECTIVES: To determine if proteins known to be expressed by both benign and malignant prostate epithelium can be recognized by T cells from patients with prostate cancer. We examined 7 HLA-A2 patients with prostate cancer for evidence of T cell reactivity with prostate-specific antigen (PSA). METHODS: Four peptides derived from PSA were chemically synthesized and shown to bind to HLA-A2. As a control, we also examined the immunogenic influenza matrix peptide Flu58-66 that binds to HLA-A2. These peptides were used to stimulate peripheral blood lymphocytes by in vitro stimulation. RESULTS: In 1 patient, specific recognition of peptide PSA141-150 was observed. The remaining 6 patients had no reactivity with any PSA-derived peptide. The T cell line with specific recognition of peptide PSA141-150 failed to recognize an autologous B cell blast line expressing endogenous PSA following infection with a recombinant PSA vaccinia virus construct. Three of the 7 patients demonstrated specific reactivity with Flu58-66. CONCLUSIONS: We found specific recognition of one PSA-derived peptide in 1 patient of 7 with prostate cancer. The peptide-specific lymphocyte cell line did not recognize endogenous PSA, suggesting that the peptide may not be produced by prostate cancer cells producing PSA. Specific recognition of PSA peptides was not common in our patients with prostate cancer. Whether such activity can be induced by vaccination strategies or can be therapeutic in men with established prostate cancer remains to be demonstrated.

Antigen-Antibody Reactions↗
PubMed1998

Serum percent free prostate-specific antigen in metastatic prostate cancer.

OBJECTIVES: To define the serum prostate-specific antigen (PSA) isoform profile in patients who have prostate cancer but do not have a prostate gland, that is, men who have had a previous radical prostatectomy (RP) and subsequently persistent disease as evidenced by elevated PSA. PSA can be reliably measured in the serum in two major isoforms: PSA complexed to alpha1-antichymotrypsin and uncomplexed free PSA (fPSA). Multiple investigations have illustrated the usefulness of the free/total PSA proportion (percent fPSA) in differentiating prostate cancer from benign prostate disease in patients who still have their prostate gland in situ. METHODS: Sera were evaluated from 52 men who underwent RP and postoperatively had increased PSA. fPSA and total PSA (tPSA) concentrations were determined using the Abbott AxSYM PSA assays. Percent fPSA was calculated for all patients. RESULTS: Median tPSA was 5.45 ng/mL (range 0.93 to 214.99). Median fPSA was 0.69 ng/mL (range 0.11 to 54.93); the median percent fPSA was 13.3% (range 3.9% to 62.9%). There were 27 (52%) patients with percent fPSA less than 15%, 25 (48%) patients with greater than 15%, and 7 (13%) with greater than 30%. No significant relationship was found between percent fPSA and grade, stage, and severity of disease. Percent fPSA was significantly increased in patients who received hormonal, radiation, or combination treatment versus those who received no treatment (P = 0.02 to 0.0007). CONCLUSIONS: Serum percent fPSA in men after RP with persistent prostate cancer encompasses a wide range of values with no clear stratifying factor or factors. These observations and further serial studies in patients with progressive metastatic disease may be important in determining the mechanism(s) for lower percent fPSA in men with newly diagnosed prostate cancer.

Aged↗
PubMed1997

Prostate-specific antigen as a screening test for prostate cancer. The United States experience.

Serum PSA-based early detection for prostate cancer has been studied fairly extensively for the past several years. It appears that we can state fairly categorically what the relative performances of total serum PSA, DRE, and TRUS are in detecting early-stage prostate cancer; that initial screening is effective in detecting histologically significant and pathologically organ-confined prostate cancer; that annual, serial, repetitive screening, at least over a 4- to 5-year horizon, does not overdetect prostate cancer, and that the results of early detection will improve as our ability to use certain PSA transformations such as PSA density, PSA slope, age-specific PSA adjustment, and knowledge of free versus total serum PSA is better characterized. These advances in our ability to diagnose early-stage prostate cancer likely will be coupled with an increased ability to predict the behavior, curability, and significance of individual tumors. It is hoped that information soon will be available to allow physicians to categorize an individual tumor as insignificant, significant and surgically curable, or significant and incurable by standard approaches. This ability, coupled with the demonstrated ability to detect prostate cancer, will make an even more compelling argument for widespread PSA-based screening. At present, annual DRE and total serum PSA measurements are recommended for men older than 50 and among younger men at high risk for prostate cancer. All suspicious DRE findings should be evaluated with prostatic biopsy. Among younger men, PSA levels over 2.5 ng/mL should be considered worrisome and further evaluated. For men older than 65, serum PSA levels above 4 ng/mL should be considered abnormal and warrant biopsy. Men with persistent serum PSA elevation and a negative biopsy should undergo repeat biopsy at least once, and perhaps more often if PSA slope exceeds 0.75 per year, if density is greater than 0.10, or if f-PSA is less than 20%.

Humans↗
PubMed2003

Total and free serum prostate specific antigen levels during the first month of acute prostatitis.

OBJECTIVES: The level of total prostate specific antigen (PSA) rises in acute prostatitis. The PSA fraction responsible for this increase and the evolution of the free/total PSA ratio are little known at the present time. We therefore carried out a prospective study of the evolution of total and free PSA levels and the free-to-total PSA ratio for one month after diagnosis of acute prostatitis. PATIENTS AND METHODS: Between January 1999 and February 2001, 31 consecutive patients (mean age 51 years) were treated for acute prostatitis. No patient had a history of prostate cancer or of recent prostatitis. Measurement of C-reactive protein (CRP), total PSA and free PSA was done at days 0, 3, 10 and 30. RESULTS: During the first month of acute prostatitis and under an adapted antibiotherapy, CRP progressively decreased and returned to normal levels at about day 10. Total PSA level increased up to day 3 and then gradually decreased until at least the end of the first month. The level of free PSA decreased up to day 10 and was still low at one month, leading to a decrease in the free-to-total PSA ratio which was reached its lowest level at day 10 and was still low at one month. CONCLUSION: The increased level of total PSA in acute prostatitis is secondary to the proportional increase in bound serum PSA and decrease in free PSA. Free PSA was still low at one month, maintaining a low free-to-total PSA ratio.

Acute Disease↗
PubMed2002

Intrafraction prostate motion during IMRT for prostate cancer.

PURPOSE: Although the interfraction motion of the prostate has been previously studied through the use of fiducial markers, CT scans, and ultrasound-based systems, intrafraction motion is not well documented. In this report, the B-mode, Acquisition, and Targeting (BAT) ultrasound system was used to measure intrafraction prostate motion during 200 intensity-modulated radiotherapy (IMRT) sessions for prostate cancer. METHODS AND MATERIALS: Twenty men receiving treatment with IMRT for clinically localized prostate cancer were selected for the study. Pre- and posttreatment BAT ultrasound alignment images were collected immediately before and after IMRT on 10 treatment days for a total of 400 BAT alignment procedures. Any ultrasound shifts of the prostate borders in relation to the planning CT scan were recorded in 3 dimensions: right-left (RL), anteroposterior (AP), and superior-inferior (SI). Every ultrasound procedure was evaluated for image quality and alignment according to a 3-point grading scale. RESULTS: All the BAT images were judged to be of acceptable quality and alignment. The dominant directions of intrafraction prostate motion were anteriorly and superiorly. The mean magnitude of shifts (+/-SD) was 0.01 +/- 0.4 mm, 0.2 +/- 1.3 mm, and 0.1 +/- 1.0 mm in the left, anterior, and superior directions, respectively. The maximal range of motion occurred in the AP dimension, from 6.8 mm anteriorly to 4.6 mm posteriorly. The percentage of treatments during which prostate motion was judged to be 5 mm. The extent of intrafraction motion was much smaller than that of interfraction motion. Linear regression analysis showed very little correlation between the two types of motion (r = 0.014, 0.029, and 0.191, respectively) in the RL, AP, and SI directions. CONCLUSION: Using an ultrasound-based system, intrafraction prostate motion occurred predominantly in the anterior and superior directions, but was clinically insignificant. Intrafraction motion was much smaller than interfraction motion, and the two types of movement did not correlate.

Humans↗
PubMed2002

Prostate-specific antigen spikes after permanent prostate brachytherapy.

PURPOSE: To evaluate whether any clinical, treatment, or dosimetric parameters correlated with the development of a prostate-specific antigen (PSA) spike after permanent prostate brachytherapy. METHODS AND MATERIALS: The evaluated population consisted of 218 hormone-naive patients free of biochemical or clinical failure who underwent permanent prostate brachytherapy with or without supplemental external beam radiotherapy for clinical Stage T1b-T3a adenocarcinoma of the prostate gland (1997 AJCC) between August 1995 and November 1999. No patient underwent pre- or postimplant hormonal manipulation, pretreatment seminal vesicle biopsy, or pathologic lymph node staging. In addition, none of the 218 patients possessed equivocal biochemical results (one or two consecutive PSA rises or a declining PSA >1.0 ng/mL). The median patient follow-up was 46.2 months. A PSA spike was defined as a rise of >or=0.2 ng/mL, followed by a durable decline. The clinical parameters evaluated included patient age, clinical T stage, Gleason score, pretreatment PSA level, prostate volume, brachytherapy planning volume, and patient follow-up in months. The evaluated treatment parameters included isotope and use of supplemental external beam radiotherapy. The dosimetric parameters evaluated included the minimal dose received by 90% of the prostate gland (D(90)), the percentage of the prostate volume receiving 100% (V(100)), 150%, and 200% (V(200)) of the prescribed minimal peripheral dose, and the mean, median, maximal, and minimal urethral doses. Biochemical disease-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition with the additional constraint that the most recent PSA level was 0.2 to 0.5 to 1.0 ng/mL (20%, 50%, and 80%, respectively, p <0.001). In Cox multivariate regression analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. A postimplant dosimetric threshold of either <115% of the minimal peripheral dose for D(90) or <55% of the prostate volume for V(150) was strongly predictive of a spike. When the variables only determinable after the occurrence of the PSA spike were included in the multivariate analysis, V(150), preimplant PSA level, and nadir PSA were the significant predictors. CONCLUSION: Of the patients, 23.9% developed a PSA spike with a median time to development of 16.3 months and a median prespike and median postspike PSA of 0.50 ng/mL and 0.90 ng/mL, respectively. In multivariate analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. At approximately 66 months after implantation, the PSA curves converged for spike and nonspike patients, with a median PSA level <0.1 ng/mL.

Adenocarcinoma↗
PubMed2006

Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases.

A major cause of treatment failure for prostate cancer is the development of androgen-independent metastatic disease. Id protein family, a group of basic helix-loop-helix transcription factors, has been shown to be involved in carcinogenesis and a prognostic marker in several types of human cancers. In this study, we examined the expressions of four Id proteins, Id-1, -2, -3 and -4, in 125 clinical prostate cancer specimens as well as 40 nodular hyperplasia specimens by immunohistochemistry. The expressions of Id proteins were correlated with Gleason grading and metastatic progress of the tumors. We found that Id proteins were dysregulated in prostate cancer. Id-1 and -2 expressions were elevated while Id-3 and -4 expressions were reduced in prostate cancers compared to nodular hyperplasia. Cytoplasmic staining of Id-1 (P=0.013) and nuclear staining of Id-2 (P=0.001) and Id-4 (P<0.001) were positively correlated with Gleason score. The results indicate that these Id proteins may play a positive role in the development of prostate cancer. In contrast, Id-3 might have an inverse relationship with prostate neoplastic transformation (P=0.002) and cancer progression (P=0.022). We found that Id-4 nuclear overexpression in the primary prostate cancers significantly increased the risks to the development of metastasis in the patients (odds ratio=3.215, 95% confidence interval=1.150-8.987, P=0.026). Our results suggest that in prostate cancer patients, differential Id proteins expressions may be a useful marker for poor prognosis, and Id-4 may be a potential prognostic marker for distant metastasis.

Aged↗
PubMed2003

Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration.

While studying Bim, a BH3-only proapoptotic protein, we identified an approximately 36 kDa protein, which was abundantly expressed in all five strains of primary normal human prostate (NHP) epithelial cells but significantly reduced or lost in seven prostate cancer cell lines. The approximately 36 kDa protein was subsequently identified as annexin II by proteomic approach and confirmed by Western blotting using an annexin II-specific antibody. Conventional and 2D SDS-PAGE, together with Western blotting, also revealed reduced or lost expression of annexin I in prostate cancer cells. Subcellular localization studies revealed that in NHP cells, annexin II was distributed both in the cytosol and underneath the plasma membrane, but not on the cell surface. Prostate cancer cells showed reduced levels as well as altered expression patterns of annexin II. Since annexins play important roles in maintaining Ca(2+) homeostasis and regulating the cytoskeleton and cell motility, we hypothesized that the reduced or lost expression of annexin I/II might promote certain aggressive phenotypes of prostate cancer cells. In subsequent experiments, we indeed observed that restoration of annexin II expression inhibited the migration of the transfected prostate cancer cells without affecting cell proliferation or apoptosis. Hence, our results suggest that annexin II, and, likely, annexin I, may be endogenous suppressors of prostate cancer cell migration and their reduced or lost expression may contribute to prostate cancer development and progression.

Amino Acid Sequence↗
PubMed2003

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy.

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.

Adenocarcinoma↗