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PubMed1997

Risk of concurrent prostate cancer in cystoprostatectomy specimens is related to volume of high-grade prostatic intraepithelial neoplasia.

OBJECTIVES: To assess the relationship of prostatic intraepithelial neoplasia (PIN) with both incidental and clinical carcinoma of the prostate. METHODS: We retrospectively reviewed prostate histology in 48 men (group 1) who underwent surgical removal of the prostate for diagnoses other than prostate cancer, as well as in 64 men (group 2) who underwent radical prostatectomies. Both groups were assessed for the presence and extent of high-grade (HG-) PIN and compared with respect to patient age, Gleason score, and volume of prostate cancer. RESULTS: HG-PIN was present in 40 of 48 (83%) group 1 cases. Forty-six percent of these cases (22 of 48) had incidental prostate cancer. Twenty-nine of 48 (60%) group 1 patients with HG-PIN had multifocal or extensive disease. Twenty of 22 (91%) incidental prostate cancers were present in 29 prostates with multifocal or extensive HG-PIN. In contrast, only 2 of 19 (11%) cases with absent to focal HG-PIN had prostate cancer. The association of multifocal or extensive HG-PIN with incidental prostate cancer was significant (P = 0.001); the relationships of extent of HG-PIN and cancer volume (P = 0.06) or high Gleason score (P = 0.017) were not significant. HG-PIN was present in 61 of 64 (95%) group 2 cases. The associations of extent of HG-PIN and cancer volume (P = 0.169) or high Gleason score (P = 0.156) were not significant. CONCLUSIONS: Both the low rate of incidental prostate cancer in specimens with absent to focal HG-PIN and the high rate of cancer in specimens with multifocal or extensive HG-PIN suggest that HG-PIN is a marker for concurrent prostate cancer and that the risk of concurrent prostate cancer is related to the volume of HG-PIN in the prostate gland.

Aged↗

PubMed1999

Clinical prostate score for diagnosis of bladder outlet obstruction by prostate measurements and uroflowmetry.

OBJECTIVES: To establish a clinical prostate score based on the parameters of uroflowmetry and prostate measurements to provide a better prediction of benign prostatic obstruction (BPO) in men with lower urinary tract symptoms (LUTS) and small prostate volume. METHODS: From October 1997 to September 1998, a prospective study of 324 consecutive men with LUTS was conducted in a community hospital in Taiwan. All patients were first evaluated by uroflowmetry and transrectal sonography of the prostate, and a videourodynamic study (VUDS) was performed before any medication was given. Patients were grouped as obstructed or unobstructed according to the results of the VUDS. Parameters from uroflowmetry and prostate measurements were evaluated for their sensitivity in predicting BPO. A clinical prostate score was established by summing scores on seven prostatic and uroflowmetric items: maximal flow rate (Qmax), flow pattern, voided volume, residual urine amount, total prostate volume (TPV), transition zone index (TZI), and prostatic configuration. Each of these items had a score representing the grade of sensitivity of BPO. RESULTS: Among the 324 men examined, only 65.4% were found to have obstruction by VUDS. A value of Qmax 10 mL/s or less had a sensitivity of only 75.4% and specificity of only 63.7% for BPO. A constrictive flow pattern had 87.2% sensitivity, residual urine 100 mL or greater had 86.1%, TPV 40 mL or greater had 94.6%, TZI 0.5 or greater had 87.8%, and the presence of a median lobe had 87.1% sensitivity; the presence of any of these factors added 2 points to the score. The other parameters were scored as 1, 0, and -1, representing their sensitivity as slightly superior or inferior to that of LUTS. A prostate score of 3 or greater had a sensitivity of 87.2% and a specificity of 60.8% for BPO. On the basis of this prostate score, 148 patients (46%) would have been treated for BPO without the need for further investigation, of whom 19 (5.9%) would have been misdiagnosed. The remaining 176 patients (54%) would have undergone a VUDS and 93 of these patients (28.7%) were unobstructed. CONCLUSIONS: By combining uroflowmetry and transrectal sonography of the prostate, patients with LUTS can be diagnosed with a good sensitivity and specificity. Using the parameters in the uroflow and prostate measurements, a prostate score could be established and used as an indicator of BPO for selecting patients with LUTS who require further treatment or invasive VUDS.

Aged↗

PubMed1998

Prostate specific antigen (PSA) value adjusted for transition zone volume and free PSA (gamma-seminoprotein)/PSA ratio in the diagnosis of prostate cancer in patients with intermediate PSA levels.

OBJECTIVES: To determine: (i) whether the accuracy of prostate-specific antigen (PSA) density is improved by using the transition zone (TZ) volume instead of total prostate volume, with the gamma-seminoprotein (gamma SP, a measure of free PSA) to total PSA ratio, for detecting prostate cancer; and (ii) to assess the influence of prostate volume on PSA density and gamma SP/PSA ratio. PATIENTS AND METHODS: From April 1995 to July 1997, 297 consecutive patients (46-88 years old) were examined; all had intermediate serum PSA levels (4-10 ng/mL) and/or abnormal findings on digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)-guided biopsy, and the prostate and TZ volumes determined from TRUS. The PSA density relative to the total prostate volume (PSAD) and to the TZ volume (PSAT) were then calculated. The total PSA and gamma SP levels were measured before the diagnostic procedures. RESULTS: Of the 297 patients, 62 (21%) were histologically confirmed to have prostate cancer by biopsy. The area under the receiver operating characteristic curve was 0.680 for PSA, 0.684 for PSAD, 0.764 for PSAT, 0.748 for gamma SP/PSA, 0.885 for gamma SP/PSA in patients with a prostate volume < 40 mL, while it was 0.817 for PSAT in patients with a prostate volume of > or = 40 mL. Using a PSAT threshold of 0.17 in patients with a prostate volume of 40 mL, the number of biopsies was reduced by 56% (66 of 118) and 22 of the 25 cancers (88%) were detected. In addition, a gamma SP/PSA ratio threshold of 40% in patients with a prostate volume of < 40 mL decreased the number of biopsies by 75% (88 of 117) and detected 32 of the 37 cancers (87%). CONCLUSIONS: Prostate volume was significantly and positively correlated with gamma SP/PSA and negatively correlated with PSAT. Among patients with a PSA level of 4-10 ng/mL, a low gamma SP/PSA was most useful for detecting prostate cancer when the prostate volume was < 40 mL and a high PSAT was useful when the prostate volume was > or = 40 mL.

Aged↗

PubMed2001

Testosterone and prostate specific antigen stimulate generation of reactive oxygen species in prostate cancer cells.

Prostate specific antigen, the clinical marker for prostate cancer, is a neutral serine protease whose function is to lyse seminal proteins. Recent work by our laboratory has suggested that prostate specific antigen stimulates the generation of reactive oxygen species in prostate cancer cells. Using 2',7'-dichlorofluorescin diacetate, a dye that fluoresces in the presence of hydrogen peroxide or hydroxyl radicals, we found that prostate specific antigen markedly stimulated reactive oxygen species generation in LNCaP cells. The effect was concentration dependent and its specificity was supported by the fact that anti-prostate specific antigen antibodies abolished the response. Since testosterone stimulates the production of prostate specific antigen, we considered that the reactive oxygen species response to testosterone may be linked to prostate specific antigen. We found that the testosterone effect on reactive oxygen species was blocked by flutamide and by anti-prostate specific antigen antibody. Additionally, though PC3 and DU145 could not respond to testosterone, they readily increased reactive oxygen species in response to prostate specific antigen. Focusing on the mechanism of the prostate specific antigen effect, we tested two other serine proteases, trypsin and chymotrypsin, but found no effect on reactive oxygen species in LNCaP cells. Nevertheless, serine protease inhibitors, alpha(1)-antichymotrypsin, alpha(2)-macroglobulin and Bowman-Birk inhibitor, blocked reactive oxygen species generation stimulated by prostate specific antigen. This apparent paradox was investigated with the use of a specific anti-'prostate specific antigen' antibody which recognizes an epitope away from the catalytic site and which does not inhibit protease activity. Despite the lack of inhibition of proteolytic activity, this antibody blocked the effect of prostate specific antigen on reactive oxygen species generation. These findings suggest that although the integrity of the prostate specific antigen molecule is necessary for stimulating reactive oxygen species generation, its proteolytic activity is not. The underlying mechanism is currently under investigation.

Blotting, Western↗

PubMed2003

The prevalence of men with National Institutes of Health category IV prostatitis and association with serum prostate specific antigen.

PURPOSE: We evaluated the prevalence and relationship of serum prostate specific antigen (PSA) levels in a screening population of men diagnosed with National Institutes of Health (NIH) category IV prostatitis. MATERIALS AND METHODS: In September of 2001, 300 men were randomly selected from our prostate cancer awareness screening program to be evaluated for NIH category IV prostatitis. After informed consent was obtained all patients completed the NIH prostate cancer awareness survey and had a serum sample obtained for PSA before examination. Expressed prostatic secretions were obtained from 227 of the 300 participants. Patients were classified according to findings on examination of the expressed prostatic secretions. The records were entered into our data base and subsequently reviewed. RESULTS: The prevalence of NIH category IV prostatitis was 32.2% in our population of men. Patient age, American Urological Association symptom scores and clinical prostate gland size did not differ between men with or without evidence of prostatitis on expressed prostatic secretion examination. Men with NIH category IV prostatitis had a mean serum PSA level of 2.3 which was significantly higher (p <0.0004) than those without prostatitis (mean PSA 1.4). CONCLUSIONS: These data suggest that NIH category IV prostatitis is fairly prevalent (32.2%) among men in the general population who present for prostate cancer screening and appears to contribute to increased serum PSA levels in some men.

Humans↗

PubMed2005

Individualization of the biopsy protocol according to the prostate gland volume for prostate cancer detection.

PURPOSE: In this study we assessed the relative yield of 10 core biopsy, and the whole range of alternative 8 and 6 core biopsy protocols over that of the classic sextant biopsy protocol. We determined the optimum number of cores per biopsy according to prostate volume in patients who experienced prostate biopsy for the first time. MATERIALS AND METHODS: A total of 503 men with the indications of abnormal digital rectal examination and/or serum prostate specific antigen greater than 2.5 ng/ml were included in the study. All patients underwent a 10 core biopsy protocol with an additional 1 core from each suspicious area detected by transrectal ultrasound. Prostate volume was divided into quartiles, namely 14.9 to 35, 35.1 to 50, 50.1 to 65 and 65.1 to 150 cc. The optimum number of biopsy cores was determined in patients with different prostate volumes. RESULTS: Median age was 63 years and prostate specific antigen was 7.4 ng/ml in the whole group. Of 503 patients 159 (31.6%) were positive for prostate cancer. Cancer detection rates decreased significantly from 49.6% to 20.8% as prostate volume increased in preset quartiles. Lesion biopsies revealed the lowest unique cancer detection rates for all prostate volume quartiles (0% to 3%). There was an obvious positive trend in cancer detection rates in favor of the 10 core biopsy protocol over sextant biopsies in all patient groups. Classic sextant biopsy protocol proved to be inadequate for all prostate volumes. Among sextant biopsy protocols laterally placed cores including the apex, lateral mid gland and lateral base had the best cancer detection rates (81% to 95%). The 8 core biopsy scheme consisting of the apex, mid gland, lateral mid gland and lateral base resulted in an only 1% lower detection rate (97%) than the 10 core biopsy protocol in the lowest quartile. The yield of the 10 core biopsy protocol in patients with a prostate volume of between 35.1 and 150 cc outscored that of the optimal 8 core biopsy scheme including the apex, base, lateral mid gland and lateral base with 3% to 8% differences in the cancer detection rate. CONCLUSIONS: The 10 core biopsy protocol must be used in all group of patients except patients with a prostate volume of 14.9 to 35 cc. In patients with a prostate volume of 14.9 to 35 cc the 8 core biopsy protocol consisting of the apex, mid gland, lateral mid gland and lateral base can be used since it revealed results similar to those of the 10 core biopsy protocol. The classic sextant biopsy protocol seemed inadequate for all prostate volumes. Patients with a larger prostate had lower cancer detection rates. Transrectal ultrasound directed lesion biopsies may be omitted when using 10 core biopsy protocols since the yield of these biopsies was less than 2%.

Adult↗

PubMed2006

The overlapping lower urinary tract symptoms of benign prostatic hyperplasia and prostatitis.

PURPOSE OF REVIEW: To investigate the relationship, diagnosis and treatment of the overlapping lower urinary tract symptoms experienced by men diagnosed with benign prostatic hyperplasia and prostatitis. RECENT FINDINGS: Recent studies have clearly shown that men can suffer from both benign prostatic hyperplasia and prostatitis. Approximately 5-20% of men diagnosed with benign prostatic hyperplasia suffer from prostatitis-like symptoms, while over one third of men diagnosed with benign prostatic hyperplasia have had a diagnosis of prostatitis in the past. Differentiation between these two symptom-based medical conditions can be difficult because of overlapping symptoms, but pain clearly identifies those patients with chronic prostatitis. Treatment for men with co-occurring benign prostatic hyperplasia and prostatitis may include alpha-blockers, 5alpha-reductase inhibitors and phytotherapies (saw palmetto and bee pollen extract), with evidence clearly showing the benefits of alpha-blocker therapy. SUMMARY: Benign prostatic hyperplasia and chronic prostatitis are a common cause of lower urinary tract symptoms and frequently co-occur in older men. The best treatment for men with lower urinary tract symptoms associated with both benign prostatic hyperplasia and prostatitis is alpha-blockers.

Adrenergic alpha-Antagonists↗

PubMed2004

The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer.

PURPOSE: The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue is not clearly known. Changes in dihydrotestosterone levels in the prostatic tissue during androgen deprivation therapy in the same patients have not been reported. We analyzed dihydrotestosterone levels in prostatic tissue before and after androgen deprivation therapy. EXPERIMENTAL DESIGN: A total of 103 patients who were suspected of having prostate cancer underwent prostatic biopsy. Sixty-nine patients were diagnosed as having prostate cancer whereas the remaining 34 were negative. Serum samples were collected before biopsy or prostatectomy. Dihydrotestosterone levels in prostatic tissue and serum were analyzed using liquid chromatography/electrospray ionization-mass spectrometry after polar derivatization. In 30 of the patients with prostate cancer, dihydrotestosterone levels in prostatic tissue were determined by performing rebiopsy or with prostate tissues excised after 6 months on androgen deprivation therapy with castration and flutamide. RESULTS: Dihydrotestosterone levels in prostate tissue after androgen deprivation therapy remained at approximately 25% of the amount measured before androgen deprivation therapy. Dihydrotestosterone levels in serum decreased to approximately 7.5% after androgen deprivation therapy. The level of dihydrotestosterone in prostatic tissue before androgen deprivation therapy was not correlated with the serum level of testosterone. Serum levels of adrenal androgens were reduced to approximately 60% after androgen deprivation therapy. CONCLUSIONS: The source of dihydrotestosterone in prostatic tissue after androgen deprivation therapy involves intracrine production within the prostate, converting adrenal androgens to dihydrotestosterone. Dihydrotestosterone still remaining in prostate tissue after androgen deprivation therapy may require new therapies such as treatment with a combination of 5alpha-reductase inhibitors and antiandrogens, as well as castration.

5-alpha Reductase Inhibitors↗

PubMed2006

Epigenetic heterogeneity of high-grade prostatic intraepithelial neoplasia: clues for clonal progression in prostate carcinogenesis.

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate adenocarcinoma, but the frequency and timing of epigenetic changes found in prostate carcinogenesis has not been extensively documented. Thus, the promoters of three genes (APC, GSTP1, and RARbeta2) involved in prostate carcinogenesis were tested by quantitative methylation-specific PCR in tissue DNA from 30 prostate carcinomas, 128 high-grade PIN lesions, and 30 normal prostate tissue samples dissected from 30 radical prostatectomy specimens using laser capture microdissection. The percentage of methylated alleles (PMA) was calculated for each gene, and hierarchical cluster analysis was used to define the degree of similarity of epigenetic alterations among the various samples. We found that PMA values of APC and RARbeta2 were higher than those of GSTP1 in all three types of tissue samples and median PMA values for all three genes were higher in prostate cancer. By cluster analysis, 26 of 30 prostate carcinomas and 82 of 128 high-grade PIN lesions were grouped in the "high methylation" branch, whereas 24 of 30 normal prostate tissue samples were allocated in the "low methylation" branch. Although high-grade PIN lesions are epigenetically more similar to prostate carcinoma than to normal prostate tissue, paired prostate carcinoma and high-grade PIN lesions did not always segregate together. We concluded that APC and RARbeta2 hypermethylation is frequent in normal prostate tissue and the progressive enrichment in cells carrying methylated alleles observed in high-grade PIN and prostate carcinoma is consistent with clonal progression. Because GSTP1 promoter methylation is mainly observed in prostate carcinoma and some high-grade PIN lesions, it represents an important marker for the transition of in situ to invasive neoplasia.

Aged↗

PubMed2004

Canine prostate carcinomas express markers of urothelial and prostatic differentiation.

Prostate carcinoma and transitional cell carcinoma (TCC) occur in the prostate gland of older dogs and have morphologic similarities when evaluated by light microscopy. The dog is a commonly used animal model for studying human prostate carcinoma; therefore, it is important to accurately differentiate canine prostate carcinomas from TCCs. We investigated whether keratin 7 (K7) and arginine esterase (AE) would aid differentiation of canine prostate carcinoma from TCC. K7 expression was evaluated in normal and neoplastic canine prostate and bladder tissues using immunohistochemistry. The expression of AE messenger ribonucleic acid (mRNA) in normal and neoplastic canine prostate and bladder was detected using northern blots and reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, AE enzyme activity was measured in normal and neoplastic canine prostate and bladder tissues. We found marked similarities in K7 expression in prostate carcinomas and TCCs. AE mRNA was present in high levels in normal prostatic tissue but was reduced in prostate carcinoma by northern blot assay. Nested RT-PCR detected AE mRNA both in TCCs (13 of 15) and in prostate carcinomas (13 of 13). Enzymatic activity of AE was high in normal prostate gland and in some prostate carcinomas, whereas normal bladder and TCCs produced lower levels of AE. In conclusion, K7 and AE cannot be used to differentiate TCC from prostate carcinoma in dogs.

Animals↗

PubMed2001

Prostate shape and symptom score in benign prostatic hyperplasia.

Prostates of the same volumes were found to have very variable shapes, that is, combinations of variably elongated width, height, and lengths. These were believed to be possible causes of the differences in the severity of both the obstructions and symptoms in the prostates even when their volumes were similar. We measured the transverse (width), anterior-posterior (height) and longitudinal (length) diameters of the prostates and the transition zone, and their calculated volumes using transrectal ultrasonography. To establish the relationship between the International Prostate Symptom Score (IPSS) and each of the dimensional parameters of the transition zone and the total prostate, 105 consecutive patients (mean age 66.43 +/- 9.24 years with a range o6f 46 to 90) who had voiding dysfunctions that were presumably related to BPH were analyzed using the t-test. Patients with conditions other than BPH were excluded. The results were as follows: 1. There was no significant correlation between the IPSS and any prostate volume parameter in the constant prostate volume conditions, because of the small numbers in each group. However, in the analysis of the total number of cases in all the volume categories, a significant correlation was found between the IPSS and some prostate dimensions; i.e., the longitudinal parameters in the total prostates (p < 0.01), and the transverse (p < 0.05) and longitudinal parameters (p < 0.05) in the transition zones. 2. Further investigations of the statistics of these significant parameters showed that prostates that were longer than 4 cm had significantly more severe symptoms than prostates shorter than 4 cm (p < 0.05), and that prostates with a ratio of length in the transition zone to the length in the total prostate ratio that was greater than 0.8 had significantly higher symptom scores than those with lower ratios (p < 0.05). When evaluating patients who have BPH, it is important to consider the shape of prostate. More aggressive treatment may be indicated in cases where the transition zone lengths exceeds 4 cm and the transition zone to total prostate length ratio exceeds 0.8.

Aged↗

PubMed2000

Prospective identification of National Institutes of Health category IV prostatitis in men with elevated prostate specific antigen.

PURPOSE: Although prostatitis may cause elevated prostate specific antigen (PSA), asymptomatic patients are not routinely screened for this diagnosis before transrectal biopsy is performed to rule out cancer. Many negative biopsies reveal evidence of prostatitis classified as National Institutes of Health (NIH) category IV prostatitis or asymptomatic inflammation. To our knowledge this report represents the initial study of the incidence of NIH category IV prostatitis in men before biopsy and its clinical significance. MATERIALS AND METHODS: From 1996 to 1998 asymptomatic men with elevated PSA levels were evaluated for laboratory signs of prostatitis. Patients with expressed prostatic secretions or post-prostate massage urine (voiding bottle 3 [VB3]) positive for greater than 20 and greater than 10 white blood cells per high power field, respectively, received antibiotics for 4 weeks and were reevaluated after 6 to 8 weeks. Men without these clinical signs promptly underwent biopsy. Those with acute urinary tract infection and PSA greater than 30 ng./ml., without a rectum or who refused biopsy were excluded from study. RESULTS: Of the 187 study patients 122 were evaluable with a mean PSA of 9.35 ng./ml., including 51 (42%) with laboratory signs of prostatitis. After treatment PSA was normal in 22 cases and remained elevated in 29, including 9 in which biopsy revealed cancer. The change or improvement in PSA was significantly greater in men with benign results than in those with prostate cancer (-21.32 versus -1.33%, p = 0.001). In the cohort with negative expressed prostatic secretion and VB3 results transrectal ultrasound guided biopsy was done promptly. Screening decreased the number of biopsies by 18% (22 of 122 cases). The positive predictive value of PSA for detecting biopsy proved cancer improved with screening for prostatitis (45 of 122 cases or 37% versus 36 of 71 or 51%). Long-term followup revealed continued normal or stable PSA in the prostatitis cohort. CONCLUSIONS: Screening for NIH category IV prostatitis should be considered in men with elevated PSA. Although patients may be asymptomatic, anxiety caused by prostate cancer and diagnostic procedures contributes to the clinical significance of this disorder.

Humans↗

PubMedDate not supplied

Prostate-specific antigen levels and subsequent prostate cancer: potential for screening.

Prostate-specific antigen levels are increased in men with prostatic disease, including prostate cancer, and have been used clinically to monitor the response of prostate cancer to therapy. More recently, prostate-specific antigen levels, usually in combination with digital rectal examination or transrectal prostatic ultrasonography, have been suggested to be useful for the detection of prostate cancer. To evaluate the association between a single serum prostate-specific antigen level and the subsequent development of prostate cancer, we measured serum levels in 35 men who donated blood to a community-based serum bank in 1974 and who subsequently developed prostate cancer and in 35 matched controls from the same group of volunteers. Levels of prostate-specific antigen were significantly higher in men who went on to develop prostate cancer, up to 6 years prior to the time of diagnosis in the cases. The level of prostate-specific antigen decreased with increasing time to diagnosis. The mean level for prostate cancer cases diagnosed within the first 3 years of follow-up was 16.2 micrograms/liter compared to 2.4 micrograms/liter for controls (P = 0.002). The mean level for cancer cases diagnosed in years 4 through 6 following blood sampling was 9.6 micrograms/liter compared to 1.3 micrograms/liter for controls (P = 0.0002). The sensitivity and specificity of a prostate-specific antigen level > or = 4 micrograms/liter up to 3 years prior to the time of clinical diagnosis were both 75% and up to 6 years were 67% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

The role of prostatic planimetry using transrectal sonography in prostatic diseases.

Transrectal sonography (TRS) remains the best method for prostatic planimetry, providing much information of value for the diagnosis and treatment of prostatic diseases, particularly of prostatic cancer. Currently, TRS is a routine tool in the detection and treatment of prostatic cancer. Prostatic planimetry is also available for a better understanding of elevated prostate-specific antigen (PSA). PSA indices modified by prostatic volume are applicable to the detection of prostatic cancer. The most critical application of prostatic planimetry is in monitoring prostatic cancer after treatment. Prostatic volume decreased exponentially after androgen deprivation therapy without exception in patients with prostatic cancer. The parameter "tau" (Tau), calculated from kinetic analysis based on sequential planimetric volumetry using TRS after the initiation of treatment, is a reliable prognosticator in an individual patient. Furthermore, tau predicts the manner of disease progression, and local or metastatic progression. Thus, transrectal ultrasonic prostatic planimetry is of special value in prostatic cancer.

Biomarkers, Tumor↗

PubMed2003

Expression study of three secretory proteins (prostatic secretory protein of 94 amino acids, probasin, and seminal vesicle secretion II) in dysplastic and neoplastic rat prostates.

BACKGROUND: Prostatic secretory protein of 94 amino acids (PSP94), probasin, and seminal vesicle secretion II (SVSII) are the three major proteins secreted by the lateral lobe of the rat prostate gland. Among these proteins, rodent PSP94 but not probasin and SVSII has a human homologue and it is also a major secretory protein of the human prostate, in addition to prostatic acid phosphatase and prostate-specific antigen. METHODS: In this study, we examined and compared the mRNA expression of these three secretory markers in three rat models of prostate cancer including the sex steroid-induced dysplasia (prostatic intraepithelial neoplasia or PIN) in Noble (Nb) rat model, an androgen-independent Nb rat prostatic tumor (AIT) and Dunning rat prostatic adenocarcinomas (both androgen-dependent and -independent) by in situ hybridization (ISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemistry. RESULTS: The transcripts for the three markers were highly expressed in the secretory epithelium of normal lateral prostate (LP). Their hybridization signals became reduced in the epithelial cells in the low-grade PINs and significantly weakened or lost in the high-grade PINs induced in the LP. Interestingly, we observed that some dysplastic cells located at the basal compartment of the PIN lesions, and nests of outpouching epithelial cells in the vicinity of PINs, expressed positive hybridization signals of three markers. In the adenocarcinoma, signals of probasin but not PSP94 and SVSII were detected. No hybridization signals were detected in both Dunning and AIT tumors. By RT-PCR, transcripts for these proteins were still detected but significantly reduced in the Dunning tumors, whereas in the AIT tumor, only SVSII transcripts were detected. Immunohistochemistry of PSP94 also showed a reduced staining in the PIN lesions, but no immunoreactivity was seen in the rat prostatic tumors. CONCLUSIONS: The mRNA expression of the three prostatic secretory markers were decreased in the hormone-induced PINs and in two rat prostatic tumors, indicating that the androgen-regulated secretory differentiation was impaired during the development of the premalignant lesion and further reduced in advanced tumors. The abnormal expression pattern of these secretory markers and androgen receptor (AR) in the basal compartment of the PIN lesions suggests that there is a population of cell types with secretory phenotype appearing in the basal cell layer during the early malignant transformation of the prostatic epithelium.

Adenocarcinoma↗

PubMed1992

Eosinophilic prostatitis and prostatic specific antigen.

Eosinophilic prostatitis is a rare form of abacterial prostatitis with uncertain aetiology. Its clinical presentation, like other types of abacterial prostatitis, commonly mimics carcinoma of the prostate. Transrectal ultrasound may be helpful in the diagnosis of prostatitis but histological confirmation is necessary. Prostatic specific antigen has been widely used in the diagnosis and follow-up of patients with prostatic carcinoma. High levels of this antigen (greater than 30 micrograms/l) have been claimed to be highly specific for prostate cancer, although lesser elevations may also occur in patients with large benign prostate glands and in bacterial prostatitis. We report 3 patients with histologically proven eosinophilic prostatitis and high levels of prostatic specific antigen. This diagnosis may closely mimic carcinoma of the prostate and must be excluded by histological examination of biopsy material before treatment for presumed prostate carcinoma is initiated.

Antigens, Neoplasm↗

PubMed1998

Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma.

BACKGROUND: Prostate carcinoma usually is heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Understanding of the molecular basis for this heterogeneity is limited, particularly for the putative precursor, high grade prostatic intraepithelial neoplasia (PIN). In this study, the authors attempted to determine the genetic relation between multiple foci of PIN and matched foci of carcinoma, and whether they are independent in origin. METHODS: The distribution and prevalence of allelic imbalance at 6 microsatellite polymorphic markers on chromosomes 7q, 8p, 8q, and 18q were examined in 84 microscopically excised PIN foci (mean, 1.6 foci/case) and 95 foci of prostate carcinoma (mean, 1.8 foci/case) from 52 completely embedded, mapped whole mount prostates. RESULTS: PIN contained a lower overall proportion of allelic imbalance than matched prostate carcinoma foci for the 6 polymorphic microsatellite markers (65% vs. 82%), but this difference was not significant. The rate of allelic imbalance in PIN was similar to that in prostate carcinoma at 5 of 6 loci studied; the exception, D18S34 (18q12.2-12.3), had a significantly lower rate of allelic imbalance in PIN than in prostate carcinoma (19% vs. 52%), suggesting that genetic alterations in this chromosomal region may be important in carcinogenesis. Of 22 cases with allelic imbalance in at least 1 focus of PIN and 1 focus of prostate carcinoma, 21 informative cases (95%) showed a similar pattern of allelic imbalance at > or = 1 markers in the matched PIN and prostate carcinoma foci. Significant genetic heterogeneity was observed in both PIN and prostate carcinoma. Allelic imbalance was observed in at least 1 focus in 11 of 25 cases with multiple foci of PIN (44%) and 20 of 25 cases with multiple foci of prostate carcinoma (80%). There was no significant correlation between allelic imbalance and pathologic stage or tumor grade. CONCLUSIONS: Our findings indicate that multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect underlies prostatic neoplasia. Multiple foci of prostate carcinoma also often arise independently, lending additional support for this hypothesis. The strong genetic similarities between PIN and prostate carcinoma strongly suggest that evolution and clonal expansion of PIN may account for the multifocal etiology of carcinomas.

Aged↗

PubMed2006

Prostate cancers scored as Gleason 6 on prostate biopsy are frequently Gleason 7 tumors at radical prostatectomy: implication on outcome.

PURPOSE: Differentiation between Gleason score 6 and 7 in prostate biopsy is important for treatment decision making. Nevertheless, under grading errors compared with the actual pathological grade at radical prostatectomy are common. We compared the characteristics and outcomes of tumors that were scored 6 on prostate biopsy but were 7 on subsequent radical prostatectomy pathological evaluation to those in tumors with a consistent rating of Gleason score 6 or 7 at biopsy and surgery. MATERIALS AND METHODS: We performed a retrospective database analysis from our referral center (1989 to 2004). We compared pre-prostatectomy characteristics, radical prostatectomy pathological features and the post-radical prostatectomy prostate specific antigen failure rate, defined as any 2 consecutive detectable prostate specific antigen measurements, in 3 subgroups of patients, including 156 with matched Gleason score 6 in the prostate biopsy and radical prostatectomy, 205 with upgraded Gleason score 6/7, that is prostate biopsy Gleason score 6 and radical prostatectomy Gleason score 7, and 412 with matched Gleason score 7 in the prostate biopsy and radical prostatectomy. RESULTS: Radical prostatectomy Gleason score matched the prostate biopsy score in 38.2% of biopsy Gleason score 6 and 81.4% of biopsy Gleason score 7 cases. Higher prostate specific antigen was associated and an increased percent of cancer in the prostate biopsy was predictive of discordance between the prostate biopsy and radical prostatectomy Gleason scores (p <0.001). Margin (p = 0.0075) or seminal vesicle involvement (p = 0.0002), cancer volume (p <0.001) and the prostate specific antigen failures rate (p = 0.014) were significantly higher in under graded Gleason score 7 cancer compared to those in matched Gleason score 6 cases. However, they were comparable to those with a matched Gleason score 7 tumor grade (p = 0.66). CONCLUSIONS: Almost half of tumors graded Gleason score 6 at biopsy are Gleason score 7 at surgery. Upgraded Gleason score 6 to 7 tumors have outcomes similar to those of genuine Gleason score 7 cancer. For prostate biopsy Gleason score 6 tumors clinicians should consider the overall likelihood of tumor upgrading as well as specific patient characteristics, such as prostate specific antigen and the percent of tumor in the prostate biopsy, when contemplating treatments that are optimized for low grade tumors, including watchful waiting or brachytherapy.

Biopsy↗