PURPOSE: Prostatitis is a common condition with a significant effect on quality of life. Even though the etiology of chronic prostatitis remains unclear, certain bacterial infections may play a major role. In recent studies, E. coli, one important etiology of urinary tract infection, was found to mediate invasion into the bladder epithelium after binding uroplakin Ia in the apical membrane of the urinary bladder. Because E. coli is also an important pathogen for bacterial prostatitis, we investigated the uroplakin mRNA expression in micro-dissected mouse prostates. MATERIALS AND METHODS: We harvested the urinary bladder, ventral prostate, dorso-lateral prostate, and coagulating gland from 3 male imprinting control region (ICR) mice. The total RNA was extracted, cDNA was prepared, and finally the five target genes--uroplakin Ia, Ib, II, III, and beta-actin were amplified. We also examined the expressed sequence tags (EST) about above four uroplakin genes from mouse EST data. RESULTS: Uroplakin Ia, Ib, II, and III were expressed in the urinary bladder. However, only uroplakin Ia was definitively expressed in the ventral prostate. Uroplakin Ib and II were weakly expressed in the ventral, dorso-lateral, and coagulating prostate. Uroplakin III was not expressed in the prostate tissue. The mouse RNA transcripts in the EST data also showed similar results to uroplakin expression in the prostate. CONCLUSIONS: These results suggest that the mouse ventral prostate may be an adequate locus for acute or chronic bacterial prostatitis study. Further in-vitro bacteriologic studies of the ventral prostate will help reveal the mechanisms of chronic bacterial prostatitis.
Actins ; Animals ; Bacterial Infections ; DNA, Complementary ; Epithelium ; Expressed Sequence Tags ; Humans ; Male ; Membranes ; Mice ; Prostate ; Prostatitis ; Quality of Life ; RNA ; RNA, Messenger ; Urinary Bladder ; Urinary Tract Infections ; Uroplakin Ia ; Uroplakin Ib ; Uroplakin III ; Uroplakins

Since the renal epidermoid cyst is too rare, the mechanisms of squamous morphogenesis have not well characterized. A 73-year-old female was referred with an incidentally detected renal pelvis mass. Abdominopelvic computed tomography scan revealed a noncalcified soft tissue mass in the renal pelvis. Total nephroureterectomy was performed under the impression of a renal pelvis malignancy. The patient was discharged without postoperative complication. The outer surface of mass lesion was lined with urothelia and squamous epithelia, containing keratinous materials. The urothelia were positively stained against uroplakin II and cytokeratin 7, whereas almost of the squamous epithelia were negative with uroplakin II. The two different epithelia were generally sharply demarcated. Interestingly, some part of squamous epithelia contained uroplakin-positive and many more cytokeratin 7-positive cells. The atypical clinical features in our case can reconsider the diagnostic clues of renal epidermoid cysts that have been reported before, and the unique immunohistochemical results may understand the histogenetic implications of the lesion.
Epidermal Cyst ; Female ; Humans ; Keratin-7 ; Keratins ; Kidney ; Kidney Pelvis ; Morphogenesis ; Postoperative Complications ; Uroplakin II ; Uroplakins

PURPOSE: The goal of this study was to constructing a nonviral vector, expressing the chimeric gene of the SV40 T antigen and mouse uroplakin II promoter (UPII promotor), which was uniquely expressed in the urothelium, to aid in the treatment of bladder cancer by the creation of a tumor that will express itself in the bladder only, but that will have no effect on the other urothelium. MATERIALS AND METHODS: 36 female C3H/He mice, weighing 20-25grams, were used in this study. A UPII-GFP-liposome complex was installed into the bladder, with Enhanced Green Fluorescent Protein (EGFP), expressing the bladder mucosa, and analyzed via fluorescent microscopy. A UPII- SV40T-liposome complex was then administered into the bladders of the mice, and the bladder and ureter examined, grossly and microscopically, at 1, 2, 3 and 4 weeks, to find transitional cell carcinomas specific to the bladder, the degree of bladder cancer development, and whether the development was from superficial to deep tumors, as well as tumor metastasis. RESULTS: The expression of EGFP was found in all four mice after 2 days. No development of tumors was evident in any mice. However, of the 6 mice sacrificed 28 days after bladder instillation, urothelial dysplasia was evident in 4. There was no evidence of transient cell carcinomas in the ureter or renal pelvis in any of the mice, or of distant metastasis during the term of the study. CONCLUSIONS: This model of bladder cancer seems to take longer than other models for cancer formation as the carcinogen affects the DNA of urothelial cell for the formation of bladder cancer. However, our bladder cancer model was better than others due to its similarity for the processes of normal bladder cancer formation.
Administration, Intravesical ; Animals ; Antigens, Viral, Tumor* ; Carcinoma, Transitional Cell ; DNA ; Female ; Humans ; Kidney Pelvis ; Liposomes ; Mice ; Microscopy ; Models, Theoretical* ; Mucous Membrane ; Neoplasm Metastasis ; Ureter ; Urinary Bladder Neoplasms* ; Urinary Bladder* ; Uroplakin II* ; Uroplakins* ; Urothelium

The apical surface of mammalian urinary epithelium is covered by numerous scallop-shaped membrane plaques. This plaque consists of four different uroplakins (UPs) and integral membrane proteins. UPs, which are a member of the tetraspanin superfamily, are assembled into plaques that act as an exceptional barrier to water and toxic materials in urine. Within the plaques, the four UPs are organized into two heterodimers consisting of UP Ia/UP II and UP Ib/UP III in the endoplasmic reticulum. The two heterodimers bind to a heterotetramer, and then assemble into 16-nm particles in the Golgi apparatus. The aggregated UP complex ultimately covers almost all the mature fusiform vesicles in cytoplasm. These organelles migrate towards the apical urothelial cells, where they can fuse with the apical plasma membrane. As a result, the UPs are synthesized in large quantities only by terminally differentiated urothelial cells. For this reason, the UPs can be regarded as a major urothelial differentiation marker. In UP knockout (KO) mice, the incorporation of fully assembled UP plaques in cytoplasm into the apical surface is not functional. The mice with UP III-deficient urothelium show a significantly reduced number of UPs, whereas those with UP II-deficient urothelium have nearly undetectable levels of UPs. This finding strongly suggests that UP II ablation completely abolishes plaque formation. In addition, UP II KO mice contain abnormal epithelial polyps or complete epithelial occlusion in their ureters. UP IIIa KO mice are also associated with impairment of the urothelial permeability barrier and development of vesicoureteral reflux as well as a decrease in urothelial plaque size. In this review, I summarize recently published studies about UPs and attempt to explain the clinical significance of our laboratory results.
Animals ; Cell Membrane ; Cytoplasm ; Endoplasmic Reticulum ; Epithelium ; Golgi Apparatus ; Membrane Proteins ; Membranes ; Mice ; Models, Animal ; Organelles ; Permeability ; Polyps ; Ureter ; Urinary Tract ; Uroplakins ; Urothelium ; Vesico-Ureteral Reflux ; Water

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. Analysis of inflammatory proteins, or cytokines in the urine or serum provides another diagnostic foundation forIC/BPS subtypes. The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. This article reviews recent research on the pathomechanisms of IC, which might help us in mapping the heterogeneity of the disease.
Adhesives ; Apoptosis ; Autoimmunity ; Biomarkers ; Cadherins ; Chondroitin Sulfates ; Cystitis ; Cytokines ; Epithelium ; Gene Expression ; Homeostasis ; Inflammation ; Lower Urinary Tract Symptoms ; Mast Cells ; Neurogenic Inflammation ; Nocturia ; Phenotype ; Population Characteristics* ; Tight Junctions ; Urinary Bladder ; Urinary Bladder Diseases ; Urinary Tract Infections ; Uroplakins

OBJECTIVETo study the effect of gene expression of mouse uroplakin II (UPII) promoter on human bladder cell cancer cell line.

METHODSThe mRNA expression of different cell lines was quantified by RT-PCR. Green fluorescent protein (GFP) and luciferase (Luc) were used as reporter genes. The plasmids carrying UPII or GFP were constructed and transfected into human cell lines of bladder transitional cell cancer (BIU-87), kindey cancer (GRC-1), vascular endothelium (EC), lung cancer cell line (A549) and skin fibroblast cell line (Hs27). GFP activity of cells was detected by confocual microscopy and flow cytometry (FCM). Luciferase value was measured by luminometer (microplate) and luciferase to beta-galactosidase ratios (L/G values) were used for evaluating transfection efficiency.

RESULTSRT-PCR showed high expression level of UPII mRNA in bladder cancer cell line BIU-87, whereas low level or no expression in nonbladder cancer cell lines. The activity of GFP in bladder cancer (BIU-87) cell was higher than that in the other cell lines (5 - 10/HP versus 0 - 2/HP), with 4.34% positive cells in BIU-87 detected by FCM, but no positive cell was found in the other cell lines. L/G values indicated that the luciferase expression in human bladder cancer cells transfected with mouse UPII promoter was 1.8 - 8.2-fold as high as that in the nonbladder cell lines.

CONCLUSIONMouse UPII promoter gene can be expressed in a tissue-specific fashion in human urinary bladder cancer. It is capable of initiating transcription of reporter genes in human bladder cancer cell line.

Animals ; Cell Line, Tumor ; Flow Cytometry ; Genetic Therapy ; Green Fluorescent Proteins ; Humans ; Luminescent Proteins ; genetics ; Membrane Proteins ; genetics ; Mice ; Organ Specificity ; Promoter Regions, Genetic ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Urinary Bladder Neoplasms ; genetics ; therapy ; Uroplakin II

PURPOSE: We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. METHODS: Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. RESULTS: In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. CONCLUSIONS: Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.
Acetic Acid ; Animals ; Animals* ; Chemokine CCL2 ; Cyclophosphamide ; Cystitis, Interstitial* ; Female ; Fibrosis ; Gene Expression ; Humans ; Hydrochloric Acid ; Hyperplasia ; Immunization ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Interleukin-6 ; Mast Cells ; Models, Animal* ; Peroxidase ; Rats* ; Rats, Sprague-Dawley ; Toll-Like Receptors ; Urinary Bladder ; Uroplakin II

OBJECTIVETo assess clinical and pathological features of ovarian transitional cell tumors.

METHODSFourteen cases of ovarian transitional cell carcinoma (TCC) were selected and investigated for their clinical and pathological features. Their immunohistochemical profiles were compared with 12 cases of serous adenocarcinoma (SC) admixed with TCC and 4 cases of EC admixed with TCC 20 cases of pure high-grade serous adenocarcinoma (HG-SC), 15 cases of endometrioid adenocarcinoma (EC), 6 cases of Brenner tumor (BT, 2 cases of malignant BT and 4 cases of benign BT).

RESULTSThe patients' age ranged from 36-63 years (mean, 56 years). All cases underwent surgery and postoperative chemotherapy with TP or CAP program. Clinical follow-up was available in 9 cases, of which 2 patients died. Histologically, all cases showed features of transitional cell carcinoma without BT component. Immunohistochemically, 13 of 14 TCCs were positive for WT-1 and all were positive for CK7, ER, PR and CA125, but negative for Uroplakin III and CK20.Similar immunohistochemical staining patterns were seen in SC admixed with TCC and pure HG-SC. Percentage of the 14 TCC cases were also diffusely positive for BRCA1. All SCs admixed with TCC and pure HG-SCs were diffusely or heterogeneously positive for WT-1, with a sharp contrast and mottled distribution pattern in the heterogeneous cases. All TCCs were diffusely and strongly positive for p53, while 16 of 20 cases of pure HG-SC were positive. The positive ratio of p53 in SCs admixed with TCC cases was 11/12.WT-1 expression in TCCs was significantly higher than BTs, ECs and ECs admixed with TCC (P < 0.01), while no obvious difference was seen when compared with SCs admixed with TCC and pure HG-SCs.SCs admixed with TCC, TCCs and EC were positive for BRCA1 except pure ECs and BTs. The positive rate of Ki-67 of BTs was low, while it was higher in TCCs, SCs admixed with TCC and pure HG-SCs. Only BTs expressed Uroplakin III.

CONCLUSIONSOvarian TCC has characteristic morphological and immunohistochemical features, similar to SC but different from BT. Therefore, TCC should be considered as a morphological variant of HG-SC.

Adult ; Brenner Tumor ; metabolism ; pathology ; CA-125 Antigen ; metabolism ; Carcinoma, Endometrioid ; pathology ; Carcinoma, Transitional Cell ; pathology ; Cystadenocarcinoma, Serous ; pathology ; Female ; Humans ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasms, Glandular and Epithelial ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Uroplakin III ; metabolism

OBJECTIVETo study the clinicopathologic features and prognosis of plasmacytoid urothelial carcinoma (PUC) of the urinary bladder.

METHODSThe clinical and pathologic findings of 16 cases of PUC were retrospectively reviewed. Immunohistochemical study (MaxVision method) was carried out. The follow-up data were analyzed.

RESULTSThere were altogether 15 males and 1 female. The age of patients ranged from 40 years to 85 years (median = 64 years). Most patients (15/16) presented with hematuria. The tumor cells were small to medium in size and contained eccentric nuclei and moderate to abundant eosinophilic cytoplasm, assuming a plasmacytoid appearance. The architectural pattern varied from loosely cohesive sheets to cords, papillae, small nests or gland-like structures. Most tumors invaded into the lamina propria or muscularis propria. Twelve of the 16 cases had concurrent conventional urothelial carcinoma component. Immunohistochemical study showed that the tumor cells in all cases were strongly positive for AE1/AE3, epithelial membrane antigen, CK7 and CK18. CK20 and uroplakin III were also expressed in 9 cases. CEA, p53, CD138, p63 and E-cadherin were positive in 12, 13, 15, 11 and 10 cases, respectively. Ki-67 index ranged from 5% to 70% (mean = 30%). All tumors were negative for vimentin, LCA, kappa/lambda light chains, S-100 protein, HMB 45,Melan A, smooth muscle actin and desmin. Follow-up information was available in 13 patients. The duration of follow up ranged from 3 months to 10 years. Three patients died of distant metastasis at 3, 27 and 60 months after the operation, respectively. One patient was alive with disease at 25 months. One was alive at 43 months with a prior recurrence. Another 8 patients were alive and disease free at 7 to 120 months.

CONCLUSIONSPUC of the urinary bladder is a rare variant of high-grade urothelial carcinoma. Immunohistochemical study with positivity for CK7, CK20, p63 and uroplakin III and negative staining for vimentin and LCA may be helpful in the differential diagnosis. PUC is a malignant tumor with high invasiveness, high recurrence rate and poor prognosis. Radical cystectomy is considered as the first line treatment for PUC.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; metabolism ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; Carcinoma, Transitional Cell ; metabolism ; pathology ; surgery ; Cystectomy ; methods ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Male ; Melanoma ; metabolism ; pathology ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Recurrence, Local ; Plasma Cells ; pathology ; Plasmacytoma ; metabolism ; pathology ; Prognosis ; Retrospective Studies ; Syndecan-1 ; metabolism ; Urinary Bladder Neoplasms ; metabolism ; pathology ; surgery ; Uroplakin III ; metabolism

A 66-year-old man with a history of multiple transurethral resections for recurrent bladder tumors, staged as Ta according to the International Union Against Cancer staging guidelines, presented with a complaint of dry cough. A round nodule with a diameter of 7.5 cm was detected in the lung by chest computed tomography, and a video-assisted thoracoscopic lobectomy was performed. Pulmonary metastasis of recurrent bladder cancer was diagnosed by immunohistochemistry staining for the urothelium-specific protein uroplakin Ia. Subsequently, 2 cycles of systemic chemotherapy were administered. Two and a half years after treatment, no recurrence of pulmonary lesions has been detected. A combination of complete resection of pulmonary lesions and systemic chemotherapy may result in a good prognosis for patients with non-muscle-invasive bladder cancer.
Cough ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunohistochemistry ; Lung ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Recurrence ; Solitary Pulmonary Nodule ; Thorax ; Urinary Bladder ; Urinary Bladder Neoplasms ; Uroplakin Ia