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Transitional cell carcinomas and nonurothelial carcinomas of the urinary bladder differ in the promoter methylation status of the caveolin-1, hDAB2IP and p53 genes, but not in the global methylation of Alu elements.

Tumor suppressor genes play a prominent role in the modification and progression of urinary bladder carcinogenesis as a result of classic genetic alterations. Little is known about the potential significance of epigenetic events, mediated by DNA hypermethylation. This prompted our investigation to explore the global Alu methylation and the promoter methylation of the novel putative tumor suppressor genes caveolin-1 and hDAB2IP, and of p53 in transitional cell carcinomas (TCC), squamous cell carcinomas and undifferentiated small cell carcinomas of the urinary bladder. Quantitative GeneScan analysis revealed that the various histopathological tumor entities showed considerable interindividual variations in the global methylation, but the overall rate did not significantly differ between the various cancer subtypes. With methylation-specific PCR, a high frequency of methylation of the promoter region of the caveolin-1 gene was detected in undifferentiated small cell carcinomas (50%) and in squamous cell carcinomas (25.9%), while TCC were found not to be methylated. By immunohistochemistry, all squamous cell carcinomas showed a strong diffuse overexpression of caveolin-1, whereas undifferentiated small cell cancers lacked any expression. High-grade, high-stage TCC disclosed a higher incidence (60%) and a substantially stronger expression than low-grade, low-stage TCC (42.9%). Our findings suggest that hypermethylation of the caveolin-1 gene and an abnormal protein expression play a crucial role in cell differentiation, and in the phenotypical conversion of TCC into nonurothelial carcinomas. Promoter methylation of the hDAB2IP gene occurred more frequently in advanced muscle invasive (72.7%) than in superficial noninvasive (50%) TCC. DNA hypermethylation of p53 was detected in a quarter of the low-grade, low-stage TCC and undifferentiated small cell carcinomas, but only sporadically in squamous cell carcinomas, and was absent in high-grade, high-stage TCC. In conclusion, aberrant methylation and abnormal protein expression of the caveolin-1-gene is involved in the formation of nonurothelial carcinomas of the urinary bladder and promoter methylation of the hDAB2IP gene in the progression of TCC from a low to a high malignant potential.

Alu Elements↗

Inverted papilloma of the urinary bladder: a case evaluated for malignant potential.

We report a case of inverted papilloma in the urinary bladder with special reference to its malignant potential. A 77-year-old male patient complaining of microhaematuria was subjected to cystoscopic examination, which showed a non-papillary pedunculated tumour at the postero-lateral wall, and was treated with transurethral resection. The histological findings of the specimen were compatible with inverted papilloma of the urinary bladder, except for the presence of low grade dysplastic changes in the tumour nuclei. We revealed the malignant potential of this tumour, analyzing and evaluating nuclear DNA content, proliferating cell nuclear antigen (PCNA) as well as p53 expression.

Aged↗

Neuroendocrine carcinoma of the urinary bladder: case report and review of the literature.

A 63-year-old Japanese man complained of hematuria and pollakisuria for several months. Computed tomography and cystography disclosed an infiltrative tumor mass in the irregularly thickened apical and posterior walls of the urinary bladder. Narrowing of the vesical lumen and posterior extension of the tumor into the pelvic cavity were also noted. After palliative ureterocutaneostomy, 60 Gy irradiation was given locally. The patient died of cachexia seven months later. Autopsy revealed neuroendocrine carcinoma of the urinary bladder with extensive invasions and metastases to the pelvic and peritoneal cavities, liver, lungs, vertebrae, left kidney and retroperitoneal lymph nodes. Histologically, atypical tumor cells with eosinophilic cytoplasm formed solid nests and anastomosing cords with pseudoglandular structures. No other histologic tumor components were included. An intact urachal remnant was found at the vesical apex while features of metaplastic cystitis were absent. In addition to positive carcinoembryonic antigen and cytokeratin, the argyrophilic cancer cells were immunoreactive for neuron-specific enolase, chromogranin A, serotonin, neuropeptide Y, glicentin, somatostatin, neurotensin and calcitonin. Ultrastructurally, neurosecretory-type granules, with a mean diameter of 166 nm, were identified in the cytoplasm of the tumor cells. To discuss the histogenesis of the tumor, 44 previously reported cases of neuroendocrine carcinoma of the urinary bladder were reviewed.

Carcinoma↗

The vertebrate urinary bladder: osmoregulatory and other uses.

The bladder may serve more biological uses than simple storage. The importance of bladder functions can be inferred from its presence among vertebrates, its anatomy and histology. From an evolutionary perspective, bladders have evolved at least twice in the vertebrates. The variability of permeability of the urinary bladder to water and solutes among species is discussed. Finally, the urinary bladder may play an osmoregulatory role.

Animals↗

Effect of substance P and capsaicin on urinary bladder of diabetic rats and the role of the epithelium.

The in vitro responses of rat urinary bladder, to substance P and capsaicin were studied at 1, 4, 16, and 26 weeks of diabetes induction by streptozotocin. We also studied the role of epithelium in these responses. The results were compared with those obtained in age-matched control rats. The bladder contractile response to exogenous substance P was similar in both groups at all stages (1-26 weeks) studied, whereas the bladder response to capsaicin gradually decreased with the progression of diabetes. Atropine did not inhibit these responses whereas indomethacin slightly reduced substance P- but not capsaicin-induced responses in control and diabetic rats. The removal of epithelium slightly increased the substance P- and capsaicin-induced responses in control tissue; these responses were significantly reduced in tissue excised from diabetic rats. Our results indicate that, in rat urinary bladder, diabetes (1) provokes an impairment of capsaicin-sensitive sensory fibers but not of the cholinergic system even at an early stage (4 weeks) of the disease, (2) has no effect on the sensitivity of smooth muscle cells to substance P, (3) stimulates the release of epithelial contracting factors, partially non-prostanoic. Furthermore epithelium removal impairs acetylcholine-induced contraction in bladder excised from diabetic rats but not in controls.

Acetylcholine↗

Expression of matrix metalloproteinases in human transitional cell carcinoma of the urinary bladder.

Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors. Especially so MMP-7, as it is mainly produced by the actual cancer cells. However, the expression of MMP-7 in transitional cell carcinoma (TCC) of the urinary bladder has not been previously investigated. We examined expressions of MMP-7 and MMP-2 in TCC, and compared them with clinicopathological characteristics in TCCs. Tumor samples from 20 patients with TCC of the urinary bladder who had surgery performed at the Osaka City University Medical School Hospital were immunohistochemically stained. Expression of MMP-2 was significantly stronger in advanced stage and high grade tumors than in low stage and low grade tumors. MMP-7 was also expressed in TCC, having a tendency to be more strongly expressed in high than in low grade tumors. However, there was no significant difference of MMP-7 expression between advanced and low stages. This increased expression of MMP-7 in high grade TCC of the urinary bladder may be associated with tumor invasion and metastasis.

Aged↗

Autonomic innervation of the equine urinary bladder.

The distribution and density of intrinsic autonomic nerve fibers and cells were studied in the equine urinary bladder by means of the peroxidase-antiperoxidase immunohistochemical method to localize tyrosine-hydroxylase (TH), and by means of a histochemical technique to detect acetylcholinesterase (AChE) activity. The results suggest that the equine urinary bladder, like that of other mammalian species, possesses a rich autonomic innervation which includes catecholaminergic and acetylcholinesterase positive nerves. At least a part of these nerve fibers have an intrinsic origin from ganglion cell bodies within the bladder wall.

Animals↗

Nephrogenic adenoma of the urinary bladder: clinical experience and review of the literature.

BACKGROUND: Nephrogenic adenoma (NA) is a rare disease of the urinary tract. We report our clinical experience with this disease in the urinary bladder and review the literature. METHODS: Between April 1994 and July 2004, 8 patients were diagnosed with NA of the urinary bladder: 3 men and 5 women, aged 23-77 years (mean 49.6). Multiple predisposing factors were analyzed. The mean follow-up time was 56 months. RESULTS: NA was not associated with transitional cell carcinoma in our series. All patients had recurrent urinary tract infection. Urinary tuberculosis was diagnosed in 2 patients. Two patients had undergone previous open urosurgery, and 4 patients had received previous endourologic management. A history of urolithiasis was found in 1 patient. Previous long-term urinary catheterization was noted in 3 patients. Two patients had received pelvic radiation therapy for cervical cancer. Urinary frequency and microscopic hematuria were found in all patients. All nephrogenic adenomas were treated with transurethral resection. Recurrent nephrogenic adenomas were diagnosed in 3 patients (median time to disease relapse, 7 months). Recurrent tumors were also treated with the endourologic method. CONCLUSION: NA is an uncommon benign metaplastic lesion occurring in the urothelium. Transurethral resection of NA provides a definite diagnosis and relief of symptoms. The recurrence rate of NA is relatively high, so careful and long-term follow-up is necessary.

Adenoma↗

Spontaneous rupture of the urinary bladder in the puerperium.

Spontaneous rupture of the urinary bladder in the puerperium is extremely rare. The patient usually presents with acute abdominal pain. Awareness on the part of the treating surgeon that bladder rupture is a possibility will lead to an early diagnosis. Immediate exploration, removing urine from the peritoneal cavity or retropubic space, closing the rupture and securing good vesical drainage, results in resumption of vesical function, and thereby decreases the mortality and morbidity.

Abdomen, Acute↗

Involvement of the urinary bladder in systemic lupus erythematosus. A pathologic study.

Urinary bladder histologic changes were found in 16 of 35 necropsies from systemic lupus erythematosus (SLE) patients in whom adequate material was available for study. These included interstitial cystitis (n = 11), hemorrhage (n = 9), congestion (n = 7), vasculitis (n = 5), and perivenular infiltrate (n = 4). Abnormalities were found in only 5 of 30 control necropsies from patients with other diseases and in 4 of them these were hemorrhagic and chiefly due to indwelling catheters. SLE patients with histologic bladder changes were found to have pulmonary hemorrhage more frequently than those without. This suggests a common pathogenetic mechanism between interstitial cystitis and pulmonary hemorrhage in SLE.

Adolescent↗

[Transitional cell carcinoma of the urinary bladder of a dog].

The occurrence of a urinary bladder transitional cell carcinoma in a dog is reported. The spontaneous occurrence of such tumours is rare in dogs and in this case no aetiological or predisposing factors for the development of this tumour could be determined. Histologically, the tumour was classified as a papillary, invasive transitional cell carcinoma.

Animals↗

High frequency of human papillomavirus infection in carcinoma of the urinary bladder.

BACKGROUND AND METHODS: The prevalence of type 6, 11, 16, 18, and 33 human papillomavirus (HPV) was investigated with the polymerase chain reaction (PCR) on formalin-fixed, paraffin wax-embedded material, including 48 neoplastic and 21 normal urinary bladder specimens. The PCR-amplified DNA were analyzed by gel electrophoresis and dot blot and Southern blot hybridization. Some tissues were tested further by nonisotopic in situ hybridization. RESULTS: HPV DNA was detected in 39 (81%) of 48 carcinomas and 7 (33%) of 21 normal urinary bladder specimens. The presence of high-risk HPV (types 16, 18, and 33) was increased significantly in carcinoma cases (62%) as compared with normal specimens (14%) (P less than 0.01). Similarly, multiple HPV infections were significantly higher in carcinoma (60%) than in the normal tissues (5%) (P less than 0.01). The overall and high-risk HPV infections in both neoplastic and normal specimens were distributed almost equally in male and female patients. There was no significant correlation between positive results for HPV and histologic grades of the carcinoma. CONCLUSIONS: These results demonstrate that the urinary bladder in both sexes is another site where infection with the common genital tract HPV may carry a risk of malignant transformation.

Carcinoma↗

Preliminary report of the clinical performance of a new urinary bladder cancer antigen test: comparison to voided urine cytology in the detection of transitional cell carcinoma of the bladder.

We compared the ability of a new urinary bladder cancer antigen (UBC) test with conventional cytology for the detection of transitional cell carcinoma of the bladder using voided urine samples. The UBC was measured and corrected for the creatinine concentration in the urine of 61 patients with transitional cell carcinoma of the bladder (group 1), 23 patients without recurrent bladder tumors during follow-up (group 2), 28 patients with benign prostatic hyperplasia (group 3), nine patients with prostate cancer (group 4), and 90 healthy volunteers free of urological diseases (group 5). The UBC concentrations were 408.8+/-578.5, 18.8+/-26.6, 23.9+/-32.7, 17.5+/-18.6 and 4.6+/-6.7 ngmg(-1) creatinine (mean+/-S. D.) for groups 1-5, respectively. The level for group 1 was significantly higher than for any other group. The sensitivity and specificity, which were optimized using receiver-operating characteristic curves for groups 1 and 2 were 82.0% and 82.6%, respectively, at a threshold value of 39 ngmg(-1) creatinine. The sensitivity and specificity of cytology for these same groups were 60.7% and 86.9%, respectively. The sensitivity of the UBC was significantly higher than that of cytology, not only for total bladder tumors (82.0% vs. 60.7%, P<0.02) but also for grade I transitional cell carcinoma of the bladder (76.5% vs. 11.8%, P<0. 001). While offering a similarly high specificity, the UBC test might have an advantage over cytology in terms of superior sensitivity, particularly for low-grade tumors.

Adult↗

Leiomyoma of the urinary bladder: case report.

A case of leiomyoma of urinary bladder, a rare benign tumour, is presented. The patient was a 42 year old female who presented with dysuria and frequency of micturition. The radiological features, diagnosis and management are discussed and the literature on this subject is briefly reviewed.

Adult↗

Muscarinic receptor binding in the guinea pig urinary bladder.

The muscarinic receptors in the guinea pig urinary bladder and the longitudinal muscle of the guinea pig ileum were studied by means of a receptor-binding technique. 1-Quinuclidinyl [phenyl 4-3H]benzilate ((-)3H-QNB) was employed as radio-ligand and the separation of bound from free (-) 3H-QNB was performed by microcentrifugation. Under conditions of equilibrium (-)3H-QNB was specifically bound with high affinity to a limited number of sites, 0.32 and 1.62 pmol/mg protein in the bladder and ileum, respectively. The binding appeared to represent a single population of non-interacting binding sites. The apparent dissociation constants were 2.6 x 10(-10) M in the bladder and 1.2 x 10(-9) M in the ileum, whereas the KD-values, estimated by extrapolation to an infinitely low receptor concentration were 1.1 x 10(-10) M (bladder) and 3.1 x 10(-10) M (ileum). The binding of (-)3H-QNB appears to represent an interaction with muscarinic receptors, as it was effectively inhibited by muscarinic antagonists and agonists, but not by a variety of non-cholinergic drugs.

Animals↗

Effect of vasoactive intestinal peptide on the contractility of the rabbit urinary bladder.

Vasoactive intestinal peptide (V. I. P.) has been demonstrated in neuronal elements of smooth muscle organs including the urinary bladder, thus indicating that this peptide may be a neurohumoral transmitter. In isolated strips of rabbit urinary bladder we have demonstrated that V. I. P. causes relaxation. Unlike the relaxant effect of the beta agonist isoproterenol, the inhibition produced by V. I. P. could not be blocked by propranolol. These studies indicate that V. I. P. may play a role in the regulation of bladder contractility.U

Animals↗

Gluteal muscular and sciatic nerve metastases in advanced urinary bladder carcinoma: case report.

We present a case of gluteal muscular and sciatic nerve metastases from urinary bladder carcinoma. T2-weighted magnetic resonance images demonstrated diffuse swelling and an increase in the signal of the right gluteus maximus muscle without destruction of the original arrangement of muscular fibers. Further, remarkable thickening of the right sciatic nerve showing a relatively hypointense signal was detected. Postcontrast T1-weighted images showed strong enhancement of these structures. Fine-needle aspiration biopsy with ultrasonographic guidance confirmed metastatic carcinoma cells in the right gluteal muscle and the sciatic nerve. These radiologic findings may represent a rare pattern of metastasis from urinary bladder carcinoma.

Adenocarcinoma↗

Immunohistochemical determinations in evaluating the prognostic in patient with urinary bladder tumors.

A set of 50 cases of urinary bladder tumors in patients predominantly resident in BEN area was histologically investigated again, in order to establish new prognostic factors. Histological type, histologic stage and invasive pattern were correlated to immunohistochemical determinations. Determinations of C-erb B2, pRb, p53 and Ki67 were performed and aggressivity degree and proliferation and prognostic indice were also established.

Adult↗