Abnormal Prostate Research Articles

P63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis

We demonstrate that deltaNp63alpha is an essential survival factor in head and neck squamous cell carcinoma (HNSCC) through its ability to suppress p73-dependent apoptosis. Inhibition of endogenous p63 expression by RNAi induces apoptosis selectively in HNSCC cells that overexpress deltaNp63alpha. Knockdown of p63 induces the proapoptotic bcl-2 family members Puma and Noxa, and both their induction and subsequent cell death are p53 independent but require transactivating isoforms of p73. Inhibition of p73-dependent transcription by deltaNp63alpha involves both direct promoter binding and physical interaction with p73. In HNSCC cells lacking endogenous deltaNp63alpha expression, bcl-2 is instead upregulated and can suppress p73-mediated death. Together, these data define a pathway whereby deltaNp63alpha promotes survival in squamous epithelial malignancy by repressing a p73-dependent proapoptotic transcriptional program.

Development of a virtual needle biopsy simulation system for the virtual prostate

AbstractThis paper discusses the virtual prostate needle biopsy system and the construction of the virtual prostate model, considering the actual distribution of prostate abnormalities. A needle biopsy simulation is performed for the constructed virtual prostate, and the actual biopsy procedure in the clinical situation is evaluated. The prostate needle biopsy is a histologic diagnosis procedure in which a sample is acquired from the prostate tissue by needle biopsy and is inspected under a microscope. In order to achieve reliable prostate needle biopsy, it is necessary to consider systematically and numerically the number of needles required, and their locations and insertion angles. For such a purpose, a system is developed in which a virtual prostate is constructed on a computer and the biopsy procedure is evaluated quantitatively by performing virtually the prostate needle biopsy. Furthermore, two different models are constructed, for the prostate with and without hypertrophy, based on the actual statistical distribution data for prostate abnormalities. Each model is partitioned into the peripheral zone and the transition zone. The constructed virtual prostate is input into the virtual needle biopsy simulation system, and three different systematic biopsy procedures actually used at clinical sites, and four different needle biopsy procedures, are experimentally evaluated. The experiments show that the insertion angle that maximizes the hit probability is not always the same as the insertion angle that maximizes cancer sample acquisition. It is evident that the proposed method can indicate a biopsy procedure which realizes a high hit probability with a small number of needles. © 2005 Wiley Periodicals, Inc. Syst Comp Jpn, 37(1): 93–104, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20181

Rosai-Dorfman disease presenting as extranodal renal mass

We present a unique case of a man presenting with an abnormal prostate and large renal mass who was ultimately found to have prostate cancer and renal Rosai-Dorfman disease. We discuss the method of diagnosis and treatment in this patient, as well as review the presentation, diagnosis, and treatment of this rare disease.

Sex steroids have differential effects on growth and gene expression in primary human prostatic epithelial cell cultures derived from the peripheral versus transition zones

The majority of human prostate cancers arise from the peripheral zone (PZ). Prostate epithelial stem cells have been localized to the basal epithelial cell compartment. In addition, basal cells have been shown to maintain luminal epithelial cell differentiation and may mediate signals between the stromal and luminal cell compartments. Therefore, the study of adult prostate basal cells derived from different prostate zones may give insights into the mechanisms underlying normal and abnormal prostate growth. We herein compare the basal and sex steroid-stimulated expression and activity of several genes/proteins that are known to be critical in prostate cancer development in primary cultures of basal cells derived from the transition zone (TZ) and PZ of prostatectomy specimens. Our results demonstrate that prostate basal cells derived from the PZ versus TZ are more viable in culture, particularly in response to sex steroid addition. PZ cells exhibit higher telomerase activity and increased expression levels of androgen receptor, the anti-apoptotic protein bcl-2, and the dominant-negative splice variant of Kruppel-like Factor 6. PZ cells have lower basal expression levels of estrogen receptor-beta, the pro-apoptotic protein Bax, and cell-cycle inhibitor proteins (p53, p21(waf1/Cip1)). Finally, we demonstrate divergent responses to sex hormones in the two basal cell populations. The gene expression pattern in the PZ cells may partially explain the predominance of prostate cancer development in this region.

Review of Clinical Manifestations of Biochemically-advanced Prostate Cancer Cases

To review the pattern of initial clinical manifestation of patients who present with biochemically-advanced prostate carcinoma. A review of 39 prostate cancer patients with initial prostate specific antigen (PSA) levels of more than 400 ng/mL (study group) and 40 patients whose initial PSA levels were between 20 and 399 ng/mL (control group) was done. The epidemiological profile and median Gleason score were similar in both groups. In the study and control groups, the median initial PSA levels were 1,000 ng/mL (range, 400-20,000 ng/mL) and 83 ng/mL (range, 21.8-337 ng/mL) respectively. Patients in the study group had statistically significantly higher incidences of bone pain, weight loss, loss of appetite, weakness in the lower limbs, and findings of abnormal prostate on digital rectal examination than patients in the control group. Significantly higher morbidity, including spinal cord compression, systemic lymphadenopathy, chronic urinary retention, elevated serum creatinine levels, anaemia and bone metastases, were also seen in the study group compared to the control group. Similar proportions of patients in the two groups developed hormone escape after treatment (50% in the study group, 45% in the control group). The cancer-specific mortality rate was 39.5% in the study group and 17.5% in the control group. There is a high incidence of excess morbidity in patients who present with biochemically-advanced prostate carcinoma.

In Utero and Lactational 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure: Effects on the Prostate and Its Response to Castration in Senescent C57BL/6J Mice

In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure inhibits ventral, dorsolateral, and anterior prostate development in C57BL/6 mice. To determine if prostatic abnormalities persist into senescence, mice born to dams given TCDD (5 mug/kg, po) or vehicle on gestation day 13 were examined at 100 and 510 days of age. Half the mice were castrated ten days prior to necropsy in order to assess androgen dependence, while the remaining mice were sham castrated. Effects of TCDD on the dorsolateral and anterior prostate of senescent sham-castrated mice were relatively subtle, whereas the ventral prostate was rudimentary or absent. Castration of vehicle-exposed mice caused far greater reductions in prostate lobe weights, epithelial cell height, and androgen-dependent gene expression (MP25 and probasin) in young mice than in senescent ones, while cell proliferation was decreased by castration in young mice and increased in senescence. Responses to castration were similar at 100 days of age in vehicle- and TCDD-exposed mice. At 510 days, however, TCDD-exposed mice were substantially more responsive to castration by most indices than vehicle-exposed mice. These results demonstrate that prostatic androgen dependence in mice declines substantially with age in several key ways, and that in utero and lactational TCDD exposure protects against this decline. Surprisingly, TCDD increased the incidence of cribriform structures in dorsolateral prostate ducts, from 2-3% in vehicle-exposed senescent mice to 16% in sham-castrated and to 7% in castrated senescent mice. Collectively, these results demonstrate that effects of in utero and lactational TCDD exposure on the prostate persist into senescence, and suggest that in utero and lactational TCDD exposure retards the aging process in the prostate. However, because cribriform structures are often considered to be associated with prostate carcinogenesis, these results also suggest that TCDD exposure early in development may increase susceptibility to prostate cancer.

INDIVIDUALIZATION OF THE BIOPSY PROTOCOL ACCORDING TO THE PROSTATE GLAND VOLUME FOR PROSTATE CANCER DETECTION

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. 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. 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. 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%.

Dynamic contrast‐enhanced MRI in normal and abnormal prostate tissues as defined by biopsy, MRI, and 3D MRSI

This study characterized dynamic contrast-enhanced (DCE) MRI of prostate tissues: cancerous peripheral zone (PZ), normal PZ, stromal benign prostatic hyperplasia (BPH), and glandular BPH. MRI, MRSI, and DCE MRI were performed on 25 patients. Tissues were identified with MRI, MRSI, and (when available) biopsy results. Motion between MRI and DCE MRI, and within DCE MRI was assessed and manually corrected. To assess tissue and patient effects, native T1's were measured in 12 of 25 patients, and DCE MRI results were normalized to muscle enhancement. Regions of cancer had a higher peak enhancement (P < 0.006), faster enhancement rate (P < 0.0008), and faster washout slope (P < 0.05) than normal PZ tissues. Stromal BPH had the fastest enhancement rate (P < 0.003) of all tissues and tended to have the greatest enhancement. Intersequence motion averaged 2.6 mm and reached 7.9 mm. Motion within DCE MRI was generally minimal (<2 pixels), but one case showed a large shift that would have confounded the results. Native T1's were similar across the prostatic tissues. Interpatient variability in DCE MRI was only partially reduced by normalization to muscle. DCE MRI of the prostate discriminated PZ cancer from normal PZ tissues and predominantly stromal and glandular BPH.

Effects of False-Positive Prostate Cancer Screening Results on Subsequent Prostate Cancer Screening Behavior

Abstract Objectives: Little is known about screening behavior following a false-positive prostate cancer screening result, which we have defined as a screening result with “abnormal/suspicious” labeling that did not result in a prostate cancer diagnosis within 14 months. The purpose of this analysis was to examine whether age, race, education, or previous false-positive prostate cancer screening results via prostate-specific antigen or digital rectal exam predict decision to obtain subsequent prostate cancer screening. Methods: Data were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The study sample consisted of 2,290 older men (mean age, 62.8 years; range, 55-75 years) who had false-positive (n = 318) or negative (n = 1,972) prostate-specific antigen or digital rectal exam baseline prostate cancer screening results. Multivariable logistic regression was used to assess the effect of false-positive results on subsequent prostate cancer screening behavior, adjusting for all covariates. Results: The multivariable model showed that being African American (P = 0.016), and having a high school education or less (P = 0.007), having a previous false-positive prostate cancer screening result (P &amp;lt; 0.001), were predictive of not returning for prostate cancer screening in the following screening trial year. Conclusion: The study results highlight the importance of shared decision making between patients and their providers regarding the risks and benefits of prostate cancer screening, and follow-up options for abnormal prostate cancer screening results. Shared decision making may be especially important for African American men, whom prostate cancer disproportionately affects.

Pathways to the diagnosis of prostate cancer in a British city. A population-based study

To identify the pathways leading to the diagnosis of prostate cancer from a UK population perspective, including the role of prostate-specific antigen (PSA) testing. We studied all 217 prostate cancers occurring in the region covered by Exeter Primary Care Trust, Devon, UK (population 128 700) between 1998 and 2002. The general practitioner's records for 2 years before diagnosis were used to identify the category of pathway to diagnosis. Symptomatic presentation to primary care initiated the diagnostic process in 166/217 men (76%). The presenting symptoms were lower urinary tract symptoms (LUTS) in 151 men (70%), systemic symptoms and no LUTS in 12 (6%) and bowel symptoms with a rectal examination revealing an abnormal prostate in 3 (1%). Eighteen cases (8%) were diagnosed as a result of PSA screening in asymptomatic men. Diagnosis as an inpatient accounted for 33 cases (15%), 25 of whom (11%) had been admitted with urological problems, and 4% of cases had been admitted for non-urological problems. Of the 151 men who presented with LUTS, 91 (60%) had a PSA test in primary care, 15 (10%) had one in secondary care and 39 (17%) had a prostatectomy that revealed a cancer that had not previously been suspected. Most prostate cancers were diagnosed after presentation to primary care with LUTS. Presentation with disseminated disease was rare. Screening by means of PSA testing remains uncommon in this area of the UK, in contrast to the situation in other countries. Most PSA tests performed in patients with prostate cancer were diagnostic rather than screening tests.

VALIDITY OF PRIMARY CARE PATIENT SELF-REPORT OF ABNORMAL (BUT NOT CANCER) PROSTATE BIOPSY RESULTS

We assessed the validity of patient self-report of abnormal (but not cancer) prostate biopsy results, ie, atypical cells or prostatic intraepithelial neoplasia. We compared survey responses and pathology records for 156 men from a multicenter, prospective cohort study, which was designed to evaluate the impact of a suspicious prostate cancer screening test followed by benign prostate biopsy. Of the 156 subjects 45 (29%) reported having had atypical cells or prostatic intraepithelial neoplasia and 38 (24%) had a pathology report with atypia or prostate intraepithelial neoplasia. The sensitivity of the self-report was 87%, specificity was 90%, positive predictive value was 73% and negative predictive value was 95%. The kappa statistic was 0.7. Men in this study reported this complex result accurately. However, it was concerning that 5 men (13%) appeared unaware of an abnormal prostate biopsy result, especially given the substantial residual risk of prostate cancer conferred by this result.

LOWER BODY MASS INDEX IS ASSOCIATED WITH A HIGHER PROSTATE CANCER DETECTION RATE AND LESS FAVORABLE PATHOLOGICAL FEATURES IN A BIOPSY POPULATION

Body mass index (BMI), calculated as weight in kg divided by the square of height in m, is used as an indicator of obesity. We assessed the relationship between BMI, and prostate cancer detection rates and biopsy features in a referral based biopsy population. A total of 787 consecutive patients referred for abnormal digital rectal examination and/or prostate specific antigen (PSA) greater than 4 ng/ml underwent systematic prostate biopsy. Three standard categories of BMI were considered, namely normal-less than 25, overweight-25 to 29.9 and obese-30 or greater kg/m. The presence or absence of cancer, percent of core involvement and tumor grade were correlated with BMI. Additional analyses controlled for patient age, PSA and prostate volume. For the entire population detection rates were highest in the normal BMI group compared to the overweight or obese group (52% vs 37% vs 42%, p = 0.0026). When stratified by age, this observation was true for men younger than 70 years (49% vs 32% vs 37%, p = 0.0042) but not for men 70 years or older. When only patients with PSA 10 ng/ml or less were considered, detection rates were highest in the normal BMI group (44% vs 28% vs 36%, p = 0.0061). This observation also persisted in patients younger than 70 years with PSA 10 ng/ml or less, or when only patients younger than 70 years with a total prostate volume of less than 50 cc were included. Of patients with cancer those with a normal BMI had a greater length of needle core involvement on biopsy. Normal BMI correlates with a higher cancer detection rate and larger cancers in men undergoing prostate biopsy.

Prostate-specific antigen doubling time as a surrogate marker for evaluation of oncologic drugs to treat prostate cancer.

With more than 230,000 new cases each year in the United States, prostate cancer is the most common cancer diagnosed among American men [(1)][1] . Prostate cancer is expected to account for nearly 30,000 deaths in the United States in 2004 and consequently represents the second most common cause of

Clinical, biochemical and pathological features of initial and repeat transrectal ultrasonography prostate biopsy positive patients.

Using sextant biopsy, 16-41% of prostate cancers were diagnosed on repeat biopsy. The objective of the present study was to compare the differences in the clinical, biochemical and pathological features between patients with positive results on initial and repeat biopsies, with an aim to identify factors that can be used to improve the detection rate of transrectal ultrasound (TRUS) biopsy of the prostate. Between February 2000 and April 2001, 222 patients with a mean age of 64 years (range 38-85) underwent TRUS-guided 10-core prostate biopsy for either abnormal prostate specific antigen (PSA) levels (>4 ng/mL) and/or abnormal digital rectal examination (DRE). Of this number, 165 patients underwent their first biopsy, whereas 45 and 12 patients had had one or two previous biopsies, respectively. Prostate cancer detection rates for the initial biopsy group (n = 165), second biopsy group (n = 45) and third biopsy group (n = 12) were 29.7, 23.0 and 41.7%, respectively. Six patients who had a negative first 10-core biopsy underwent a second 10-core biopsy and one patient (16%) was found to have cancer. Apart from total prostate volume, there were no significant statistical differences between the patient age, mean total PSA, PSA density, PSA-transition zone density, DRE and TRUS findings between the initial and repeat biopsy groups of subjects who had cancer. Those who had cancer detected only on repeat biopsies had larger prostate glands (P = 0.041). Patients who had cancer detected only on repeat biopsies had bigger prostate glands, supporting the hypothesis that TRUS sextant biopsy as a technique suffers the error of under-sampling in a bigger prostate.

Aryl hydrocarbon receptors in urogenital sinus mesenchyme mediate the inhibition of prostatic epithelial bud formation by 2,3,7,8-tetrachlorodibenzo- p-dioxin

In utero exposure of male C57BL/6 mice to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) prevents prostatic epithelial buds from forming in the ventral region of the urogenital sinus (UGS) and reduces the number of buds that form in the dorsolateral region. This inhibition of budding is aryl hydrocarbon receptor (AHR) dependent and appears to be the primary cause of lobe-specific prostate abnormalities in TCDD-exposed mice. TCDD can inhibit prostatic epithelial bud formation by acting directly on the UGS in vitro, but whether it does so via AHR in UGS mesenchyme, epithelium, or both was unknown. To address this issue, UGS mesenchyme and epithelium from gestation day (GD) 15 wild-type C57BL/6J male mice were isolated, recombined, and cultured in vitro for 5 days with 10 −8 M 5α-dihydrotestosterone (DHT) and either 10 −9 M TCDD or vehicle. Prostatic epithelial buds were viewed by light microscopy after removal of mesenchyme. Effects depended greatly on which portions of the mesenchyme were used: TCDD had little if any effect when whole UGS epithelium (UGE) was recombined with ventral plus dorsolateral mesenchyme, tended to reduce bud numbers in recombinants made with UGE and dorsolateral mesenchyme, and severely reduced bud numbers in recombinants made with UGE and ventral mesenchyme (VM). [VM + UGE] recombinants prepared from wild-type and AHR knockout ( Ahr −/−) mice were then cultured with DHT to determine the site of action of TCDD. AHR null mutation alone had no effect on budding. TCDD severely inhibited prostatic epithelial bud formation in recombinants that contained mesenchymal AHR, whereas bud formation was not inhibited by TCDD in recombinants lacking mesenchymal AHR, regardless of epithelial AHR status. These results demonstrate that UGS mesenchyme and not UGS epithelium is the site of action of TCDD. Therefore, the initial events responsible for abnormal UGS (and ultimately prostate) development occur within the UGS mesenchyme, and changes in gene expression in the UGS epithelium responsible for inhibited prostatic budding are secondary to the direct effects of TCDD on UGS mesenchyme.

Asymptomatic Follicular Lymphoma of the Prostate Discovered by Abnormal Digital Rectal Examination

Prostatic lymphoma is rare, with fewer than 100 reported cases. Patients initially present with local and generalized symptoms, with obstructive uropathy being the most common clinical presentation.1–3 We report on an asymptomatic male who had an abnormal prostate on routine digital examination and was subsequently diagnosed with follicular lymphoma. CASE REPORT An asymptomatic 69-year-old black male had a diffusely enlarged, hard and fixed prostate on routine digital rectal examination, suggesting a malignant process. The remaining physical examination was unremarkable and without lymphadenopathy. Family history was noncontributory. The prostate was 62 cc, asymmetrical (right lobe greater than left) and diffusely hypoechoic on ultrasound. Serum prostate specific antigen was normal (1.84 ng/ml).

Lyn is a target gene for prostate cancer: sequence-based inhibition induces regression of human tumor xenografts.

The Src-related protein kinase Lyn plays an important role in B-cell activation. However, several lines of evidence suggest that it is also involved in the control of cellular proliferation and the inhibition of apoptosis. We have discovered that Lyn is expressed in normal prostate epithelia, in 95% of primary human prostate cancer (PC) specimens examined, and in all of the PC cell lines that we assayed. Moreover, Lyn knockout mice display abnormal prostate gland morphogenesis, which suggests that Lyn plays an important role in prostate epithelium development and implies that Lyn is a candidate target for specific therapy for PC. Using a drug-design strategy to construct sequence-based peptide inhibitors, a Lyn-specific inhibitor, KRX-123, targeting a unique interaction site within Lyn, was synthesized. KRX-123 was found to inhibit cellular proliferation in three hormone-refractory PC cell lines, DU145, PC3, and TSU-Pr1 with IC(50) values of 2-4 micro M. In vivo, tumor volume of DU145 explants in nude mice was significantly reduced after once-a-week injections of KRX-123, at a dose of 10 mg/kg, for a period of 5 weeks. Histological analyses of the treated tumors indicated extensive apoptosis. Thus, we suggest that Lyn inhibition may serve as a prime target for the treatment of hormone-refractory PC.

Pigment Epithelium-Derived Factor, a Human Testis Epididymis Secretory Product, Promotes Human Prostate Stromal Cell Growth in Culture

We identified and characterized unrecognized testicular secretory proteins that impact human prostate growth. Human spermatocele fluid served as a source of testicular epididymal secretions and prostatectomy specimen benign prostatic hyperplasia stromal cells as the in vitro prostate growth promoting effects indicator. RMPI plus medium supplemented with 10% fetal bovine serum MALDI-TOF, MS FBS and ITS+ (Collaborative Research-Becton Dickinson, Bedford, Massachusetts) served as positive and negative controls, respectively. Whole and fractionated spermatocele fluid or specific proteins without and with select polyclonal or monoclonal antibodies were added to routine 6-day cultures. The observation of significantly increased 6-day cell counts compared with appropriate controls (p <0.05) was judged to reflect cell growth. Amino acid microsequencing and MALDI-TOF MS sequence analysis were done on persistent protein bands from active spermatocele fluid fractions. Whole and fractionated human spermatocele fluid increased stromal cell culture numbers significantly. Sequence analysis of 47 and 17 kDa 1-dimensional gel bands in the final active fraction identified a major peptide with sequence homology to human pigment epithelium-derived factor (PEDF). The presence of PEDF was confirmed by Western blot analysis. Addition of recombinant PEDF to incomplete medium significantly increased stromal cell culture number. PEDF antibodies neutralized or markedly decreased the stromal stimulating effect of spermatocele fluid and PEDF. The observations presented provide evidence for human testis/epididymis secretion of PEDF and for a PEDF in vitro growth promoting effect on benign prostatic hyperplasia stroma. The concept that testicular epididymal secretory proteins may influence normal and abnormal prostate growth warrants continued consideration.

Benign Prostatic Stromal Hyperplasia With Bizarre Nuclei

A 37-year-old healthy Hispanic man was referred for an enlarged prostate noted during routine physical examination. The patient denied any urological symptoms and reported no previous health problems. Serum prostatic specific antigen was 62.85. Computerized tomography (CT) of the abdominopelvic region demonstrated a 10 10 cm mass with multiple heterogeneous densities in the pelvis between the bladder and the rectosigmoid (fig. 1). No other abnormalities were noted on CT. Chest x-ray was clear. Cystoscopy showed a normal bladder and no significant prostatic abnormalities. Prostate volume was 135 cc and there was diffuse heterogeneous echogenicity noted on transrectal ultrasound. Prostatic needle biopsies revealed fibromuscular stroma with spindle cells having atypical nuclei grouped in a multinucleate pattern and proliferation suspicious for malignant stromal tumor (fig. 2). Histological staining demonstrated cytoplasmic positivity for CD34, desmin and estrogen. Repeat biopsy was performed due to concern regarding sampling error. Repeat microscopic findings were similar to the first set of biopsies. Bizarre giant cells with vacuoles and multinucleation were seen. No mitotic figures or necrosis was present. The histomorphology of the mass was most consistent with prostatic stromal hyperplasia with bizarre nuclei.

The Androgen Cascade in Ageing Men: Blessing or Curse?

Dihydrotestosterone (DHT) is a dominant force in the development of the adult prostate. The action of DHT is critical in modulating the interaction of epithelial cells in the urogenital sinus mesenchyme during the organogenesis of the prostate. During adolescence, DHT is required to complete the normal growth phase of the prostate. In older men, if the response to DHT is altered, the resulting population of cells may be dominated by the transient proliferation of intermediate cells that are very sensitive to DHT for their ‘amplifying’ potential. In benign prostatic hyperplasia, these mechanisms are disturbed and the usual control of final stromal and epithelial cell mass is ineffective. The importance of the two isozymes of 5α reductase in regulating the continuing stromal:epithelial cell balance might provide a good scientific basis for moderating both pathways in an attempt to alter the clinical consequences of abnormal prostate growth.