Molecular Detection of Pathogens Causing Sexually Transmissible Infections in Patients with Prostate Cancer and Hyperplasia by Quantitative TaqMan Real-Time PCR Assay.

BACKGROUND: Prostate cancer is considered the most prevalent cancer among men. Recent studies suggest that sex-ually transmissible infections (STIs) may be related to prostate carcinogenesis. Therefore, the aim of this study was to investigate whether STI pathogens (Atopobium vaginae (ATO), Neisseria gonorrhoeae (NG), Chlamydia tra-chomatis (CT), Treponema pallidum (TP), Ureaplasma urealyticum (UU), Gardnerella vaginalis (GV), Herpes Sim-plex Virus (HSV), Cytomegalovirus (CMV), Human herpesvirus (HHV), Human papillomavirus (HPV), and Tricho-monas vaginalis (TV)) presence in prostate tissues are associated with the risk of prostate cancer. METHODS: Paraffin-embedded prostate tissues obtained from patients with hyperplasia and prostate cancer were extracted. Determination of infectious microorganisms of interest was done by quantitative TaqMan real-time PCR assay. RESULTS: STI DNA was detected in 53/243 (21.8%) of the prostate tissues samples (ATO 3.7%, UU 2.88%, GV 2.46%, HSV-2 2.05%, CT 2.05%, CMV 1.64%, NG 1.64%, TP 1.64%, HHV-8 1.23%, HPV 1.23%, and TV 1.23%.) The statistical analysis revealed significant correlation between prevalence of Gardnerella vaginalis (GV) and Herpes Simplex Virus (HSV-2) between hyperplasia and cancerous groups (p = 0.02), respectively. CONCLUSIONS: No statistically significant difference was observed in the prevalence of most candidate infectious or-ganisms between hyperplasia and cancerous groups except for GV and HSV-2. It appears that inflammation in the prostate gland is more associated with prostate hyperplasia than prostate cancer. According to the role of in-fectious microorganisms in induction of chronic inflammation, we cannot exclude the importance of these patho-gens in progression of cancer. More studies are required to explore the associations of cancer with different infec-tious organisms.

Inflammation-associated pathologies in a case of prostate schistosomiasis: Implications for a causal role in prostate carcinogenesis.

BACKGROUND: Urogenital infection with Schistosoma haematobium is a risk factor for the development of squamous cell carcinoma of the urinary bladder. The pathophysiology is thought to be mediated in part by inflammation, cellular damage, and bladder regeneration induced by the parasitic infection. Herein, we report an unusual case of schistosomiasis of the prostate that was found concurrent with prostate adenocarcinoma in a radical prostatectomy specimen from a man in the United States. METHODS: The infecting Schistosoma species was characterized via histomorphology and acid-fast stain. The concurrent Gleason score 6 prostate cancer was assessed for ETS transcription factor ERG (ERG), phosphatase and tensin homolog (PTEN), p27, and p53 status using immunohistochemistry (IHC). Cellular proliferation and the presence of intermediate cells in prostatic atrophy were assessed via immunostaining for Ki67 and CK903, respectively. RESULTS: Histomorphology and acid-fast stain of the infecting species were consistent with S. haematobium. We classified the Gleason score 6 prostate adenocarcinoma via IHC as ERG positive, PTEN intact, p27 intact, and without p53 nuclear accumulation. The prostatic epithelium immediately adjacent to the schistosomiasis-related granulomatous inflammation was atrophic and accompanied by increased cellular proliferation and the presence of intermediate cells. Upon literature review, we determined that prostate schistosomiasis is associated with a young age of prostate cancer diagnosis and highly aggressive prostate cancer. CONCLUSIONS: This is a rare case of prostate schistosomiasis in the United States; however, prostate schistosomiasis occurs frequently in endemic areas. The patient had traveled to a Schistosoma-endemic region, which was the likely location of exposure to the parasite. To our knowledge, this is the first report of the association of proliferative inflammatory atrophy and intermediate cells with schistosomiasis of the prostate. We propose that prostate schistosomiasis may be considered as a risk factor for the development of prostate cancer in geographic regions where Schistosoma species are endemic.

Inflammatory mediators of prostate epithelial cells stimulated with Trichomonas vaginalis promote proliferative and invasive properties of prostate cancer cells.

BACKGROUND: Trichomonas vaginalis (Tv) is the most common sexually transmitted parasite. It is detected in prostatic tissue of benign prostatic hyperplasia, prostatitis, and prostate cancer (PCa) and has been suggested to cause chronic prostatitis. Moreover, up to 20% of all cancers worldwide are associated with chronic inflammation. Here, we investigated whether inflammatory mediators produced by normal human prostate epithelial cells (RWPE-1) stimulated with Tv could promote growth and invasiveness of PCa cells. METHODS: Conditioned medium of RWPE-1 cells was prepared by stimulating them with Tv (trichomonad-conditioned medium [TCM]) and without Tv (conditioned medium [CM]). Promotion of PCa cells (PC3, DU145, and LNCaP) was assessed by wound healing, proliferation, and invasion assays. RESULTS: We observed that the production of interleukin (IL)-1ß, IL-6, CCL2, CXCL8, prostaglandin-E2 (PGE2 ), and COX2 by RWPE-1 cells was increased by stimulating them with Tv. When PCa cells were incubated with TCM, their proliferation, invasion, and migration increased. Moreover, they showed increased epithelial-mesenchymal transition (EMT)-related markers by a reduction in epithelial markers and an increase in mesenchymal markers. In vivo, xenograft tumor tissues injected with TCM also showed increased expression of cyclin D1 and proliferating cell nuclear antigen, as well as induction of EMT. Receptors and signal molecules of PCa cells increased in response to exposure to TCM, and blocking receptors (CXCR1, CXCR2, C-C chemokine receptor 2, glycoprotein 130, EP2, and EP4) reduced the proliferation of PCa cells with decreased production of cytokines (CCL2, IL-6, and CXCL8) and PGE2 , and expression of NF-κB and Snail1. CONCLUSIONS: Our results suggest that Tv infection may be one of the factors creating the supportive microenvironment to promote proliferation and invasiveness of PCa cells.

Association between Trichomonas vaginalis and prostate cancer mortality.

We previously observed a positive association between seropositivity for the parasite Trichomonas vaginalis and risk of clinically significant prostate cancer at diagnosis. Here, we examined whether T. vaginalis seropositivity was associated with increased prostate cancer-specific or all-cause mortality among prostate cancer patients. We studied 736 men with prostate cancer from the Physicians' Health Study (PHS) and 749 men with prostate cancer from the Health Professionals Follow-Up Study (HPFS). We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between T. vaginalis serostatus and progression to death from prostate cancer and from all causes. In PHS, 423 men died of any cause during a median follow-up of 13.8 years from the date of cancer diagnosis, among whom 131 died of prostate cancer. In HPFS, there were 287 deaths, including 77 deaths from prostate cancer, during a median follow-up of 12.8 years. We found no association between T. vaginalis serostatus and either prostate cancer mortality or all-cause mortality in either the PHS or HPFS. While previous studies suggest a possible role for T. vaginalis in the development of clinically significant prostate cancer, our findings do not support the hypothesis that T. vaginalis serostatus is associated with mortality among prostate cancer patients.

Iodine-125 seeds in prostatic transurethral resection: Differential diagnosis with schistosome eggs.

The presence of foreign bodies in a prostate transurethral resection may pose a histopathological challenge. A 65-year-old white man with urinary obstructive symptoms was subjected to a transurethral resection. Histopathology showed a squamous cell carcinoma affecting prostatic ducts and multiple foreign bodies; their differential diagnosis was between iodine-125 seeds and Schistosoma sp. eggs, as both can show oval morphology and terminal spines. The seeds are irregular, homogeneous and solid, unlike Schistosoma eggs that are heterogeneous, with a lytic appearance and some embryonated or calcified. The seeds are located in prostatic ducts inducing periductal fibrosis whereas the Schistosoma sp. eggs are found in the stroma inducing desmoplasia and granulomas. The seeds are associated with a lymphoplasmacytic infiltrate while the eggs are surrounded by eosinophils.

Schistosoma Egg Antigen Induces Oncogenic Alterations in Human Prostate Cells.

Schistosomiasis is a neglected tropical disease that affects 200 million people and accounts for 100,000 deaths annually. In endemic geographical areas, schistosomiasis has been implicated as an etiological agent in the pathogenesis of bladder, colorectal, and renal carcinoma largely due to Schistosoma eggs in tissues that comes with chronic infection. Several studies have also reported cases of association between Schistosoma infection and prostate cancer. The possible causal association is however poorly understood. We hypothesized in this study that infection of the prostate cells with Schistosoma spp promotes cancer. Urine samples from individuals living in Galilea, a schistosomiasis endemic community in the Ga South District of Ghana, were collected and screened for Schistosoma infection via microscopy and multiplex PCR. Soluble egg antigens (SEA) were prepared from Schistosoma egg-positive urine samples and assessed for the ability to induce cancer-like phenotypes including excessive proliferation, oxidative stress (reduced glutathione (GSH) depletion), and diminished apoptosis in cultured human prostate (PNT2) cells. Molecular analysis revealed infecting schistosome species to be S. haematobium and S. mansoni. Prostate cell proliferation was significantly induced by 12.5 µg/ml SEA (p = 0.029). Also, SEA dose-dependently depleted cellular GSH. Flow cytometric analysis and fluorescence staining revealed that SEA dose-dependently diminished apoptosis, significantly, in prostate cells. Findings of this study suggest that schistosome infection may play a role in the pathogenesis of prostate cancer. In vivo studies are however needed to confirm this association.

Interaction between Trichomonas vaginalis and the Prostate Epithelium.

Most men infected with Trichomonas vaginalis are asymptomatic and can remain undiagnosed and untreated. This has been hypothesized to result in chronic persistent prostatic infection. Adhesion of the protozoan organisms to mucosal cells is considered a first and prerequisite step for T. vaginalis infection. Adhesion of T. vaginalis to prostate epithelial cells has not yet been observed; however, there are several reports about inflammation of prostate epithelial cells induced by T. vaginalis. The aim of this study was to investigate whether adhesion and cytotoxicity of T. vaginalis are involved in inflammation of prostate epithelial cells. When RWPE-1 cells were infected with T. vaginalis (1:0.4 or 1:4), adhesion of T. vaginalis continuously increased for 24 hr or 3 hr, respectively. The cytotoxicity of prostate epithelial cells infected with T. vaginalis (RWPE-1: T. vaginalis=1:0.4) increased at 9 hr; at an infection ratio of 1:4, cytotoxicity increased after 3 hr. When the RWPE-1 to T. vaginalis ratio was 1:0.4 or 1:4, production of IL-1ß, IL-6, CCL2, and CXCL8 also increased. Epithelial-mesenchymal transition (EMT) was verified by measuring decreased E-cadherin and increased vimentin expression at 24 hr and 48 hr. Taken together, the results indicate that T. vaginalis adhered to prostate epithelial cells, causing cytotoxicity, pro-inflammatory cytokine production, and EMT. Our findings suggest for the first time that T. vaginalis may induce inflammation via adhesion to normal prostate epithelial cells.

Cystic Echinococcosis: One Entity, Two Unusual Locations.

We report two cases of cystic echinococcosis at unexpected locations. Patients were a 64-year-old man and 35-year-old woman. A cystic mass was incidentally found between the prostate and seminal vesicles in the male patient, using ultrasonography during a check-up for ischemic coronary disease. The female patient was admitted to the hospital with symptoms of cardiopulmonary disease, but her detailed radiological examination showed a cystic lesion in the interventricular septum of the heart. Both patients were operated, and examinations of the histologic sections revealed cyst walls consistent with echinococcal infection. Attention should be focused on this entity even in endemic areas, and pathologists should be aware of the histologic characteristics of this lesion, to avoid misdiagnosis as a nonspecific cyst.

Prostate adenocarcinoma associated with prostatic infection due to Schistosoma haematobium. Case report and systematic review.

Schistosomiasis affects more than 240 million people worldwide, an infection which may cause urogenital manifestations including, among others, squamous bladder cancer and prostate involvement. We describe the first case of a prostate adenocarcinoma associated with prostatic Schistosoma haematobium infection occurring in Angola. Prostate carcinoma was suspected because of high levels of prostate-specific antigen. This observation prompted us to review the literature on schistosomiaisis with respect to genital pathology and prostate cancer. Described genital manifestations in men include funiculitis, epididymitis, granulomata of the seminal vesicles, testicular masses, and prostate lesions which may cause haematospermia and infertility. In contrast to bladder cancer, only 12 reports including the present case on 17 cases on prostate carcinoma associated with schistosomiasis have been published worldwide. The rarity of reports on prostate carcinoma associated with schistosomiasis is partly due to diagnostic constraints, and its incidence is underestimated. However, in emerging countries, the incidence of prostate cancer appears to increase mainly as a result of urbanization and improved access to health care where schistosomiasis prevalence is decreasing.

Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.

The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.

Schistosomiasis of the prostate: a case report.

BACKGROUND: Schistosomiasis with involvement of the prostate is relatively uncommon and is rarely diagnosed in needle core biopsies. CASE: A 45-year-old, African American man who had recently returned from the Middle East presented with hematospermia of unknown etiology. He also had an elevated PSA level and a positive family history of prostate cancer. Prostate needle core biopsies were obtained. On microscopy he had multiple foci of acute and chronic inflammation. In other foci, Schistosoma haematobium ova were identified in the absence of a host inflammatory response. All his biopsies were negative for carcinoma. A diagnosis of schistosomiasis of the prostate was made. CONCLUSION: Schistosomiasis should be considered in the differential diagnosis of parasitic diseases involving the prostate, especially in patients who live in or have recently visited endemic regions.

Prostatic Schistosoma japonicum with atypical immunophenotyping of individual glandular tubes: a case report and review of the literature.

There are few cases of prostatic schistosomiasis. Here we report a case of Schistosoma japonicum of the prostate, in which the immunophenotyping of individual glandular tubes was atypical. Whether the S. japonicum infection contributed to the lesion or not is unknown. We suspect the lesion was a sign of early precancerous hyperplasia. Follow-up of this patient may give clues about the relationship between schistosomiasis and prostate cancer. This is the first case report of prostatic S. japonicum in the English literatures. A review of the literature is carried out.

Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host∶parasite interactions.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization.

Trichomonas vaginalis contact-dependent cytolysis of epithelial cells.

Trichomonas vaginalis is an extracellular protozoan parasite that binds to the epithelium of the human urogenital tract during infection. In this study, we examined the propensities of 26 T. vaginalis strains to bind to and lyse prostate (BPH-1) and ectocervical (Ect1) epithelium and to lyse red blood cells (RBCs). We found that only three of the strains had a statistically significant preference for either BPH-1 (MSA1103) or Ect1 (LA1 and MSA1123). Overall, we observed that levels of adherence are highly variable among strains, with a 12-fold range of adherence on Ect1 cells and a 45-fold range on BPH-1 cells. Cytolysis levels displayed even greater variability, from no detectable cytolysis to 80% or 90% cytolysis of Ect1 and BPH-1, respectively. Levels of adherence and cytolysis correlate for weakly adherent/cytolytic strains, and a threshold of attachment was found to be necessary to trigger cytolysis; however, this threshold can be reached without inducing cytolysis. Furthermore, cytolysis was completely blocked when we prevented attachment of the parasites to host cells while allowing soluble factors complete access. We demonstrate that hemolysis was a rare trait, with only 4 of the 26 strains capable of lysing >20% RBCs with a 1:30 parasite/RBC ratio. Hemolysis also did not correlate with adherence to or cytolysis of either male (BPH-1)- or female (Ect1)-derived epithelial cell lines. Our results reveal that despite a broad range of pathogenic properties among different T. vaginalis strains, all strains show strict contact-dependent cytolysis.

High detection rate of Trichomonas vaginalis in benign hyperplastic prostatic tissue.

While Trichomonas vaginalis, a protozoan parasite, is a well-investigated pathogen in the female population, there is little awareness of its significance in the male uro-genital tract. The presence of T. vaginalis in the prostate gland has only been scarcely investigated and has never been attested in conditions other than clinical prostatitis. Still, by some authors, this organ is regarded as ecologic niche for T. vaginalis. Since normal prostate tissue of sufficient quality is hard to come by, we investigated samples from 86 patients (mean age 68.7 ± 7.6 years) suffering from benign prostatic hyperplasia (BPH), a medical condition currently ranked as noninfectious, but characterized by chronic inflammatory tissue infiltrates of unknown etiology. Applying two different PCR protocols and sequence analysis of the respective amplicons, we detected T. vaginalis DNA in 29/86 (34%) BPH tissue samples, whereas in only 2/86 (2.3%) cases T. vaginalis grew in culture. Detection of T. vaginalis DNA correlated significantly (P < 0.01) with elevated peripheral blood monocytic cell counts, appearing along with protozoan infections. Given the unexpected high prevalence of T. vaginalis in BPH tissue of a nonselected, elderly study population from Austria, further epidemiological studies have to confirm this finding. Potential interactions of T. vaginalis in its prostatic habitat may be investigated with respect to their possible contribution to the inflammatory pathogenesis of BPH, since inflammatory cytokines have been shown to sustain prostatic hyperplastic growth.

Transrectal high-intensity focused ultrasound for local treatment of prostate cancer: current role.

Attractivity of robotic high intensity focused ultrasound (HIFU) is based largely on the non-invasive, extremely precise nature of this high-tech robotic therapy as well as its clean, radiation free, surgical, but nevertheless, bloodless character. Today, in urological oncology, HIFU is used clinically as a therapeutic tool for the treatment of prostate cancer. Experimentally it is investigated for therapeutic use in kidney and breast cancer. Transrectal treatment of localized prostate cancer with HIFU has been under investigation since the 1990s and it is meanwhile an actively used therapy for the disease in many urological departments worldwide. Since 2000 HIFU is mostly used in combination with transurethral resection of the prostate in order to reduce prostate gland size, to facilitate effective tissue destruction and to avoid side effects. Palliative and salvage indications as well as focal therapy of prostate cancer are under investigation to extend the spectrum of HIFU indications for non invasive prostate cancer therapy.

Association between prostate cancer and schistosomiasis in young patients: a case report and literature review.

This case report refers to a 47-year old patient with prostate cancer associated with schistosomiasis mansoni, who was submitted to radical prostatectomy. This is the third report published in the literature with respect to this association, and up to the present time it is still not known whether a cause and effect relationship exists between the two pathologies. The association between schistosomiasis and cancer has been well-documented in bladder cancer; however, there are no data yet proving the association of this disease with prostatic neoplasia. In this report, a third documented case of prostatic adenocarcinoma and schistosomiasis mansoni is described and a literature review is performed.

Association between prostate cancer and schistosomiasis in young patients: a case report and literature review

This case report refers to a 47-year old patient with prostate cancer associated with schistosomiasis mansoni, who was submitted to radical prostatectomy. This is the third report published in the literature with respect to this association, and up to the present time it is still not known whether a cause and effect relationship exists between the two pathologies. The association between schistosomiasis and cancer has been well-documented in bladder cancer; however, there are no data yet proving the association of this disease with prostatic neoplasia. In this report, a third documented case of prostatic adenocarcinoma and schistosomiasis mansoni is described and a literature review is performed.

Plasmodium chabaudi chabaudi chronic malaria and pathologies of the urogenital tract in male and female BALB/c mice.

BALB/c mice of both sexes were infected with a non-virulent strain of Plasmodium chabaudi chabaudi and any pathologies occurring in the urogenital tract and its accessory glands were investigated. Organs and tracts were removed from infected and control mice at 15, 40 and 100 days post-injection, weighed and processed for macroscopical and histological analyses. The relative weights of preputial, clitoral glands and testes were modified in infected mice during the 40 days following infection. The preputial glands show a marked hypotrophy at 15 days post-infection. The bladders of half of the infected female mice and a few infected male mice displayed a conspicuous haemoglobinuria and frequent interstitial cystitis that worsened throughout the experiment. Also, several chronic inflammatory reactions were detected in the prostates, preputial and clitoral glands up to 100 days post-infection. A probable cause of such a divergence in the characteristics of the infection and in the nature of the pathologies identified in infected male and female mice is the interaction between the infection and the immune and endocrine systems of the host. The cause of the pathologies and their consequences on the host condition are discussed.

Concomitant prostatic schistosomiasis and adenocarcinoma: case report and review.

The term schistosomiasis encompasses a group of infectious disorders caused by five species of the genus Schistosoma, a blood trematode of outstanding importance in tropical areas. Some of these disorders have long been associated with malignant neoplasia, the most striking association being between disease caused by Schistosoma haematobium, the predominant etiological agent of urinary schistosomiasis, and squamous cell carcinoma of the bladder, a relatively uncommon vesical cancer in non-endemic areas. Four cases of simultaneous adenocarcinoma and schistosomiasis of the prostate have been previously reported (S. haematobium in three and S. mansoni in one). We report a fifth case of concomitant adenocarcinoma and schistosomiasis of the prostate in a 68-year-old Brazilian patient infected with S. mansoni. We also review the medical literature on the association between schistosomiasis and cancer.