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A 65-year-old man undergoes a routine checkup before retiring. His wife has urged him to have his prostate examined, because she has read about testing for prostate cancer and a friend has just died of this disease. During the rectal examination, the man''s physician discovers some firmness in the right lobe of the prostate gland. The patient has had no urinary symptoms and is in excellent general health. Sexual function is normal. There is no history of prostate cancer; his father died of a stroke at age 86 years. Testing shows that the patient''s prostate-specific antigen level is 9.3 ng/mL, and he is referred to a urologist. Transrectal ultrasound-guided needle biopsy reveals adenocarcinoma with a Gleason score of 7 (intermediate grade). At a follow-up meeting with his physician, the patient says, "I have been doing some research, and it appears that I should have treatment. However, what is less clear to me is what form of therapy is best--surgery or radiation treatment. Please tell me what you can about the state of the art with respect to surgery."     

Gonadotropin-Releasing Hormone Agonist-Induced Pituitary Apoplexy in Treatment of Prostate Cancer: Case Report and Review of Literature

ObjectiveTo describe a case and review the literature on the rare complication of pituitary apoplexy after administration of a gonadotropin-releasing hormone agonist (GnRHa) for treatment of patients with prostate cancer.MethodsWe present a detailed case report of a patient with immediate signs of pituitary apoplexy after receiving a GnRHa and review the 6 previously reported cases in the literature.ResultsA 60-year-old man presented to a local hospital with severe headache, nausea, vomiting, and diplopia. Prostate cancer had recently been diagnosed, and he had received his first dose of a GnRHa 4 hours before this presentation. On physical examination, he was confused and had ptosis of the left eye. A head computed tomographic scan without contrast enhancement showed soft tissue filling the sella, without intracranial hemorrhage or mass effect. He was discharged with the diagnosis of viral meningitis. Three weeks later, he presented again with severe headache and diplopia. He had confusion, lethargy, disorientation, a blood pressure of 88/64 mm Hg, and left cranial nerve III, IV, and VI paralysis. Magnetic resonance imaging of the brain revealed an enhancing pituitary mass with hemorrhage extending to the optic chiasm, consistent with pituitary apoplexy. Laboratory results were consistent with panhypopituitarism. Surgical excision revealed a necrotic pituitary macroadenoma with hemorrhage. Tumor immunohistochemical staining was positive only for luteinizing hormone.ConclusionWe describe a rare adverse effect of GnRHa therapy, which unmasked a gonadotropin-secreting pituitary macroadenoma. This case adds to the 6 previously reported cases of GnRHa administration inducing pituitary apoplexy in men with prostate cancer. (Endocr Pract. 2007;13:642-646)     

Psoriasis exacerbation after hormonotherapy in prostate cancer patient—Case report

Psoriasis, as the most common inflammatory skin disorder, affects about 2–3% of the world''s population. Many non-dermatological conditions have been linked with psoriasis, including cardiovascular diseases, depression, inflammatory bowel disorders, and some cancers, i.e. lung, colon and kidney cancers. Among systemic factors are endocrine and metabolic disturbances as well as many drugs. Erythrodermic psoriasis, the most severe form of the disease, is characterized by diffuse erytrema and scaling, often accompanied by fever, chills, and malaise.A 57-year-old Caucasian man was admitted for curative radiation therapy of adenocarcinoma of the prostate after 3 months of initial hormonal therapy. The management comprised the combined androgen blockade (CAB). On admission the patient reported escalation of psoriasis symptoms, which he had been treated for since 2002. Due to a mild course of the disease he had not required any systemic treatment ever before, even during aggravation periods. The last exacerbation started appearing a month after hormonal therapy implementation. The cutaneous eruptions, already existing, become larger with new foci revealing, mainly on upper and lower limbs. During radiotherapy planning, there appeared a diffuse erythema and scaling on hands and feet with accompanying pruritis. We decided to start the previously planned radiation therapy which included the prostate gland with 1.5 cm margin and provided for the total dose of 72 Gy in 36 fractions. The irradiation was conducted with the four-field technique using a megavoltage linear accelerator. During radiotherapy we photo-documented skin lesions.To our best knowledge hormone therapy (androgen deprivation) of prostate cancer patients has not been reported as an aggravating factor. Thus, the aim of our work is to present the case of a prostate cancer patient who experienced psoriasis exacerbation after implementation of hormonal blockade as a neoadjuvant oncological treatment.     

TRH-related peptides in the rabbit prostate complex during development.

The novel peptide, pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2), has recently been isolated and characterized from the rabbit prostate complex. The tripeptide is present in high concentrations in the prostate complex and semen, together with a 40-50 residue polypeptide which contains a TRH-immunoreactive fragment at its C-terminus. The present study investigates changes in the levels of these TRH-related peptides in rabbits aged 11 weeks, 4 months, 7 months, 13 months and 2 years. For each age group the peptides were extracted from the prostate complex, separated by gel exclusion chromatography, and located by TRH radioimmunoassay. The TRH-immunoreactive fragment was released from the polypeptide by trypsin digestion prior to radioimmunoassay. Very low concentrations of TRH-immunoreactive peptides were present at 11 weeks of age, but considerable levels of both peptides were found in all the other age groups. Anion exchange chromatography, under conditions which resolve TRH and pGlu-Glu-ProNH2, showed that the majority of the low molecular weight TRH immunoreactivity co-eluted with synthetic pGlu-Glu-ProNH2. The remaining TRH immunoreactivity, which had not bound to the anion resin, also failed to bind to a cation exchange column at pH 2.0, indicating that it was not authentic TRH. Dissection of the prostate complex into its four constitutive regions (vesicular gland, coagulating gland, prostate and bulbourethral gland) followed by extraction, chromatography and TRH radioimmunoassay of each region showed that the TRH-related peptides were located in the prostate.     

Adrenalectomy and Castration in the Genetically Obese (OB/OB) Mouse

The present studies have tested the hypothesis that adrenalectomy could modify the phenotypic expression of genetic obesity by examining the effects of adrenalectomy on the function of the gonadal system in lean and ob/ob mice. Corticosterone concentrations were undetectable in the adrenalectomized animals. Adrenalectomy significantly slowed the weight gain of obese mice in comparison to sham-adrenalectomized controls. Gonadectomy had no independent effect on weight gain. The testes, prostate, and seminal vesicles in the ob/ob mice were significantly smaller than in the lean animals. Castration lowered the weights of the prostate and seminal vesicles in the lean mice to weights close to those observed in the castrated ob/ob mice. Castration significantly increased the concentrations of LH and FSH in both ob/ob and lean mice, but the absolute concentrations were higher in the lean mice in both conditions. Adrenalectomy per se had no effect on the concentration of LH, FSH, or testosterone or on the weights of the prostate or seminal vesicles. These data indicate that adrenalectomy has no effect on the physiologic control of the reproductive system in genetically obese mice, and are consistent with the hypothesis that the defect in the ob/ob mouse is a modulator of steroid action which over expresses glucocorticoid effects and under expresses gonadal steroid effects.     

Morphological and functional heterogeneity in the rat prostatic gland.

Ductal morphogenesis and adult ductal branching patterns were examined in the rat prostate by a microdissection method. The rat prostate consists of paired (right and left) subdivisions which correspond in large part to the classically defined lobes: ventral prostate, lateral prostate, dorsal prostate, and coagulating gland. Of particular interest was the finding that the lateral prostate consists of two different ductal zones: (1) lateral type 1 prostate with 5-7 long main ducts (resembling miniature palm trees) that extend cranially towards both the seminal vesicle and dorsal prostate to arborize near the bladder neck, and (2) lateral type 2 prostate with 5-6 short main ducts that arborize caudal to the bladder neck and give rise to compact bushy glands. Both lateral prostatic groups had a ductal-acinar organization. The adult structure of the other rat prostatic lobes was also examined, and closely resembled their mouse counterparts. The ventral prostate, which had 2-3 pairs of slender main ducts per side, and the coagulating gland, which had 1 main duct per side, was completely ductal in structure. In contrast, the dorsal prostate, which had 5-6 pairs of main ducts per side, had a ductal-acinar structure. Ductal branching morphogenesis occurred at different rates in different lobes and was essentially complete in the prostate at the 30 days. Immunocytochemical studies with an antibody to DP-1, a major secretory protein of the rat dorsal prostate, revealed that secretory function was initiated at approximately 30 days after birth in the coagulating gland, the dorsal prostate, and lateral type 1 prostate. A consistent feature of the lateral type 2 prostate was the absence of DP-1. On Western blots, DP-1 was detected in the secretion of the coagulating gland, lateral type 1 and dorsal prostate, but not in the ventral and lateral type 2 prostate. Polyacrylamide gel electrophoresis confirmed this result and demonstrated that the lateral type 2 prostate expressed several low-molecular weight secretory proteins not found in the other lobes of the prostate. On the whole, the rat prostate exhibited considerable heterogeneity both between and within lobes in developmental processes, ductal patterning, histology, and functional expression.     

Lycopene: modes of action to promote prostate health

Epidemiological evidence strongly suggests that lycopene consumption contributes to prostate cancer risk reduction. Preclinical studies show that lycopene acts via different mechanisms, which have the potential to cooperate in reducing the proliferation of normal and cancerous prostate epithelial cells, in reducing DNA damage, and in improving oxidative stress defense. The mechanisms include inhibition of prostatic IGF-I signaling, IL-6 expression, and androgen signaling. Moreover, lycopene improves gap-junctional communication and induces phase II drug metabolizing enzymes as well as oxidative defense genes. These findings provide plausible explanations for the epidemiological findings how lycopene can contribute to reduced prostate cancer risk. The novel finding that lycopene reduces local androgen signaling in the prostate suggests also efficacy in prevention of benign prostate hyperplasia. Intervention trials in humans are required to finally prove clinical efficacy of the lycopene molecule in prostate health.     

Effect of estrogen administration on activities of testosterone 5alpha-reductase, alkaline phosphatase and arginase in the ventral and the dorsolateral prostates of rats.

Daily treatment with 5 or 500 mug of estradiol benzoate of male adult rats for 7 days did not change the activity of testosterone 5alpha-reductase in the ventral prostate, while the activity decreased slightly in the dorsolateral prostate. The activity of alkaline phosphatase was increased by 60% over the respective control in the ventral prostate from rats treated with the larger dose of estrogen, but the estrogen treatment did not affect the alkaline phosphatase activity in the dorsolateral prostate. On the contrary, the estrogen treatment evoked three-fold elevation in the arginase activity of the dorsolateral prostate in contrast to the decreased arginase activity in the ventral prostate following estrogen administration. From these results, it was concluded that the alterations in some enzyme activity of the ventral and the dorsolateral prostates evoked by estrogen treatment were different from those observed in the respective lobes from castrated animals, although both estrogen administration and castration induced atrophy of the tissue. Furthermore, it might be also worth-while to mention that the ventral and the dorsolateral prostates of rats responded in a different manner to estrogen administered.     

Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics

While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1–14.3 (LOD = 2.4), and 20p11.21–q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13–22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives. The names of all authors and their affiliations are listed in the Acknowledgements. The fact that Dr Schaid’s name is given here for purposes of correspondence should not be taken to imply that he played the sole leading part in writing this article. An erratum to this article can be found at     

Le test urinaire PCA3 : quelles perspectives ?

Since its introduction 10 years ago, the urinary PCA3 test was evaluated in several studies that allowed demonstration of its diagnostic value when predicting prostate biopsy outcome. Its good specificity, notably when compared to seric PSA, offers to the urologist the opportunity to better evaluate whether prostate biopsies are warranted, especially in patients with at least one set of previous negative biopsies. Several points remain to be determined such as its true influence on prostate decision making in clinical practice and the resulting medico-economic benefit. The place of the urinary PCA3 test among other developing prostate cancer biomarkers, notably PHI index and urinary TMPRSS2:ERG fusions, has also to be defined.     

Prostate cancer: 1. The descriptive epidemiology in Canada

A 70-year-old woman who experienced a long period of depression after her first husband''s death from prostate cancer at the age of 63 has become increasingly anxious about her own health and that of her close family. A few years ago she married a man her own age; he is in good physical condition. Last year the family spent much of the winter in Florida, where the woman noticed several studies in the media suggesting that an epidemic of prostate cancer is occurring in North America and that because early detection can save lives men of retirement age should be checked by their physicians as soon as possible. In addition, 2 close friends recently diagnosed with prostate cancer. On his latest fishing trip her husband learned from a friend that 1 in 8 men get prostate cancer. He has not seen his family physician for several years, but his wife has booked an appointment for them to discuss their concerns.     

Genomic signatures associated with the development, progression, and outcome of prostate cancer

Prostate cancer remains a common cause of cancer death in men. Applications of new genomic technologies to the recent development of high-quality prostate cancer models in multiple contexts have added great molecular insight into the development of and progression to metastasis. Genomic analysis of DNA, RNA, and protein alterations allows for the global assessment of this disease and provides the molecular framework to improve risk classification, outcome prediction, and development of targeted therapies. The creation of expression profiles and signatures will allow the evaluation of cancer phenotypes and give insight into determining those with increased risk of cancer, identification of critical pathways involved in the development of cancer, prediction of disease outcome, and assessment of the response of cancer to established and novel therapies.This review focuses on highlighting recent work in genomics and on its role in evaluating potential genetic modifiers of prostate cancer and novel biomarkers that may help with prostate cancer diagnosis, its potential to provide a better understanding of prostate cancer behavior and transition to metastatic disease, and its role in current and new therapies in prostate cancer. This framework has the exciting potential to be predictive and provide personalized and individual treatment to the large number of men diagnosed with prostate cancer each year.     

Risk of prostate,ovarian, and endometrial cancer among relatives of women with breast cancer.

OBJECTIVE--To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN--Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING--Iceland. SUBJECTS--The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES--Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. RESULTS--The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. CONCLUSIONS--Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations.     

The EZC-prostate model: noninvasive prostate imaging in living mice

Recently, progress in the development of prostate-specific promoters and high resolution imaging techniques has made real-time monitoring of transgenic expression possible, opening a vista of potentially important in vivo models of prostate disease. Herein, we describe a novel prostate reporter model, called the EZC-prostate model that permits both ex vivo and in vivo imaging of the prostate using a sensitive charge-coupled device. Firefly luciferase and enhanced green fluorescent protein were targeted to the prostate epithelium using the composite human kallikrein 2 (hK2)-based promoter, hK2-E3/P. In EZC-prostate mice, the ventral and dorsal/lateral prostate lobes were brilliant green under fluorescence microscopy, with expression localized to the secretory epithelium. In contrast, enhanced green fluorescent protein was undetectable in the anterior lobes of prostate, seminal vesicles, testes, liver, lung, and brain. The kinetics of luciferase activity in intact and castrated living mice monitored with the IVIS charge-coupled device-based imaging system confirmed that firefly luciferase expression was largely prostate restricted, increased with age up to 24 wk, and was androgen dependent. Decreases in reporter expression after 24 wk may reflect well known, age-related decreases in androgen signaling with age in humans. Ex vivo imaging of microdissected animals further confirmed that the luminescence detected in living mice emanated predominately from the prostate, with minor signals originating from the testes and cecum. These data demonstrate that the hK2-E3/P promoter directs strong prostate-specific expression in a transgenic mouse model. Multigenic models, generated by crosses with various hyperplastic and neoplastic prostate disease models, could potentially provide powerful new tools in longitudinal monitoring of changes in prostate size, androgen signaling, metastases, or response to novel therapies without sacrificing large cohorts of animals.     

An A/G polymorphism of core 2 branching enzyme gene is associated with prostate cancer

The expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1 (C2GnT) is associated with development and progression of malignancy. Sequence analysis showed that the codon 152 of C2GnT has a polymorphism having GTT encoding valine or ATT encoding isoleucine. By examining the polymorphism in prostate cancer and benign prostatic hyperplasia patients, we found that the C2GnT G allele was more frequently observed in the prostate cancer group (p=0.015) than the control group. Men with the GG genotype had a 3.60-fold increased risk of prostate cancer, and men with the AG genotype had a 1.58-fold increased risk of prostate cancer compared with those with the AA genotype. The G allele was found to have a gene dosage effect for prostate cancer risk. No such risk was associated for benign prostatic hyperplasia. These results demonstrate that C2GnT A/G polymorphism is associated with the susceptibility to prostate cancer in a Japanese population.     

Magmas expression in neoplastic human prostate

Magmas, is a 13-kDa mitochondrial protein which is ubiquitously expressed in eukaryotic cells. It was identified as a granulocyte-macrophage-colony stimulating factor (GM-CSF) inducible gene in hematopoietic cells and has a key role in the transport of mitochondrial proteins in yeast. Because GM-CSF receptor levels are elevated in prostate cancer, Magmas expression was examined in normal and neoplastic tissue. Magmas protein levels were barely detectible in non-neoplastic prostate glands. Increased amounts were observed in some samples of intraepithelial neoplasia. Approximately one half of the adenocarcinoma samples examined had weak Magmas expression, while the remainder had intermediate to high levels. The increased Magmas observed in malignant tissue was a result of higher protein expression and not from changes in mitochondrial content. Interestingly, in some patients, the normal prostate tissue had more Magmas message than the malignant portion. The results indicated that Magmas expression in prostate cancer is heterogeneous and independent of clinical stage and Gleason score. Further studies are needed to determine if Magmas expression has prognostic significance in prostate cancer.