Transitional Cell Carcinoma Of Urinary Bladder Research Articles

Risk of Osteosarcoma in Dogs After Open Fracture Fixation.

To critically evaluate whether open fracture fixation is a significant risk factor for latent osteosarcoma development. Case-control study. Dogs undergoing open fracture repair and dogs diagnosed with osteosarcoma. Records were retrieved from the Veterinary Medical Database VMDB (1970-2000) for dogs undergoing surgical repair of a fracture and dogs diagnosed with osteosarcoma. Dogs with open reduction of joint luxation, dogs diagnosed with bacterial cystitis, and dogs diagnosed with urinary bladder transitional cell carcinoma (UBTCC) were queried as comparison populations. Relative risk for osteosarcoma development was determined. From a population of 19,041 fractures treated surgically, 15 of those dogs subsequently appeared in the VMDB with osteosarcoma affecting the same bone. The relative risk of a fracture repair and associated orthopedic implants and osteosarcoma occurrence was equivalent to the relative risk of open joint reduction and osteosarcoma occurrence (95% confidence interval; 0.998-1.00). The relative risk of having bacterial cystitis and appearing again in the VMDB with UBTCC was higher than the risk of open fracture repair and a subsequent diagnosis of osteosarcoma (P < .02). The incidence of fracture-related osteosarcoma may be significantly less than previously estimated based on cases queried from the VMDB. Although possible cases of implant-associated osteosarcoma were identified, their occurrence was rare. Elective implant removal for the purpose of reducing the risk of osteosarcoma after fracture repair may not be warranted and merits further investigation.

Metastatic urinary bladder transitional cell carcinoma to the oral cavity and oropharynx

Background Distant metastasis from urinary bladder transitional cell carcinoma (TCC) is a well-reported phenomenon, most commonly occurring in osseous and pulmonary sites. In contrast, metastasis to oral and/or oropharyngeal soft tissues is extremely rare.

Multiple Subcutaneous Nodular Metastasis from Transitional Cell Carcinoma of the Urinary Bladder in a Dog

A 10-year-old spayed female Pomeranian dog weighing 3.65 kg was presented with a 7-month history of urinary incontinence, stranguria and hematuria. The patient had mass lesions at left prescapular region (3 cm × 3 cm) and left axillary region (5 cm × 4 cm). Diagnosis of transitional cell carcinoma (TCC) with multiple cutaneous metastasis was made. Dog was treated with chemotherapy using mitoxantrone and piroxicam for 5 months. Although TCC size of urinary bladder was decreased during chemotherapy, there was no change of subcutaneous tumor size and mild relief of clinical signs. Partial anorexia for 3 weeks and multiple masses were noted at left caudal abdominal wall and left medial thigh (203 days after first presentation) and assessed as chronic kidney disease and additional subcutaneous metastasis of urinary bladder TCC by post-mortem and histopathological findings.

GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder.

To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer. Case-control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found that carriers of mutant GSTO2*G/G genotype were at increased risk of the development of TCC (OR 2.6, 95% CI 1.2-5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk (p = 0.450). According to smoking status, smokers with GSTO2*G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95% CI 1.6-11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1/GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) (D' = 0.309, p = 0.001). The study subjects with GSTO1*C/GSTO2*G (GSTO1 wild-type/GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95% CI 1.5-5.2, p = 0.002). Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2*G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking.

Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis)

This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC) of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis), from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urinary bladder. The nodule had a soft consistency and arised from the mucosa of the urinary bladder extending throughout the muscular layers and the serosa. Nodules of similar appearance infiltrating the vertebral column the at L6 and L7 vertebrae with corresponding spinal canal invasion were also observed. The histological evaluation showed epithelial neoplastic proliferation in the urinary bladder with characteristics of nonpapillary and infiltrative TCC, with positive immunohistochemical staining for pancytokeratin, and strong immunostaining for cytokeratin of low molecular weight, and weak or absent labeling for high molecular weight cytokeratin. This is the first report of TCC of urinary bladder in ocelot in Brazil.

The expression sequence tag is an effective method for screening DNA segments that predict urinary bladder transitional cell carcinoma prognosis.

PurposeWe validated the use of expression sequence tags (ESTs) as an effective method of screening for DNA segments that could predict urothelial cell carcinoma and for identifying ESTs with such predictive value.Patients and methodsFrom 2004 to 2009, eleven patients were enrolled in this study: six with high-grade bladder carcinoma and five with low-grade bladder carcinoma. ESTs were used to screen for differential gene expression in a high-grade cell line (MGH-U1) and in a premalignant cell line (MGH-U4). Immunohistochemistry and real-time reverse transcription-polymerase chain reaction were used to validate the degree of EST expression and the prognostic value of ESTs.ResultsApoferritin H subunit (FTH1 protein) exhibited increased expression in high-grade bladder carcinoma compared with that seen in low-grade carcinoma. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction both supported the higher expression of FTH1 in high-grade urothelial carcinoma.ConclusionESTs are useful for detecting the FTH1 protein, which predicts the prognosis of patients with bladder carcinoma.

Frequent expression of zinc-finger protein ZNF165 in human urinary bladder transitional cell carcinoma

The aim of the study is to evaluate mRNA/protein expression of zinc finger protein 165 (ZNF165) in transitional cell carcinomas (TCCs) of urinary bladder and correlate its expression with the clinicopathological characteristics of patients. In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were utilized to evaluate mRNA/protein expression of ZNF165 in TCC. Independent Student's t test, ANOVA and Chi-square (χ2) were used to analyze the data statistically. We observed overexpression of ZNF165 mRNA in testis and majority (59.2%) of TCC patients. ZNF165 mRNA expression was also detected in adjacent noncancerous tissues (ANCTs) and some other normal tissues. Relative mean fold expression of ZNF165 mRNA was found to be significantly (p<0.01) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients. (12.11±9.57 vs. 5.72±2.61, p=0.009). ZNF165 protein expression was demonstrated on archival formalin-fixed, paraffin-embedded (FFPE) bladder tissues using IHC and nuclear staining pattern was detected. No significant difference was observed in protein expression of ZNF165 between the two groups (NMIBC and MIBC patients) (61.1% vs. 55.2%, p=0.629). No significant protein expression of ZNF165 was observed among ANCTs and benign prostatic hyperplasia (BPH) used as control. Our study results suggest that ZNF165 mRNA/protein expression was observed in TCC of human urinary bladder and might be used as a novel diagnostic biomarker and as well a vaccine target in development of urinary bladder cancer specific immunotherapy.

Expression and clinical significance of Centrosomal protein 55 (CEP55) in human urinary bladder transitional cell carcinoma

Bladder cancer (BC) is one among the most common and lethal urothelial malignancies worldwide. The expression of cancer-testis (CT) antigens in some tumours and restricted expression among normal tissues make CT antigens as attractive vaccine targets. In this context, we evaluated Centrosomal protein 55kDa (CEP55), which is specifically expressed in normal human testis and various malignancies. Until the expression pattern of CEP55 in transitional cell carcinoma (TCC) of human urinary bladder and its clinical significance are not known. The aim of the present study is to evaluate mRNA/protein expression of CEP55 in TCCs of urinary bladder and correlate its expression with the clinicopathological characteristics of BC patients. In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to investigate mRNA/protein expression of CEP55 in TCC. Independent Student's t test, ANOVA and Chi-square (χ2) were used to analyze the data statistically.We observed CEP55 mRNA overexpression in testis and 48.7% of BC patients. Relative mean fold expression of CEP55 mRNA was found to be significantly (p<0.01) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients (7.88±3.88 vs. 4.75±2.30, p=0.01). CEP55 protein expression was evaluated using IHC and cytoplasmic staining pattern was recorded in formalin fixed, paraffin-embedded (FFPE) bladder tumour tissues. No significant difference was observed in protein expression of CEP55 between the two groups (NMIBC and MIBC patients) (72.2% vs. 69.0%, p=0.774). No significant protein expression of CEP55 was observed among adjacent noncancerous tissues (ANCTs) and benign prostatic hyperplasia (BPH) used as control. Our study results suggest that CEP55 mRNA/protein expression was observed is specific to TCC of human urinary bladder and might be used as a diagnostic biomarker and vaccine target in development of BC specific immunotherapy.

Two-year carcinogenicity study in rats with a nonnucleoside reverse transcriptase inhibitor.

Administration of lersivirine, a nonnucleotide reverse transcriptase inhibitor, daily by oral gavage to Sprague-Dawley rats for up to 2 yr was associated with decreased survival, decreased body weights, and an increase in neoplasms and related proliferative lesions in the liver, thyroid, kidney, and urinary bladder. Thyroid follicular adenoma and carcinoma, the associated thyroid follicular hypertrophy/hyperplasia, hepatocellular adenoma/adenocarcinoma, altered cell foci, and hepatocellular hypertrophy were consistent with lersivirine-related induction of hepatic microsomal enzymes. Renal tubular adenoma and renal tubular hyperplasia were attributed to the lersivirine-related exacerbation of chronic progressive nephropathy (CPN), while urinary bladder hyperplasia and transitional cell carcinoma in the renal pelvis and urinary bladder were attributed to urinary calculi. Renal tubular neoplasms associated with increased incidence and severity of CPN, neoplasms of transitional epithelium attributed to crystalluria, and thyroid follicular and hepatocellular neoplasms related to hepatic enzyme induction have low relevance for human risk assessment.

Clinical utility of urinary soluble Fas in screening for bladder cancer

Early diagnosis of carcinoma of urinary bladder remains a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Soluble Fas (sFas), a cell-surface receptor and member of the tumor necrosis factor superfamily, is frequently expressed in urinary bladder carcinoma. The objective of this study was to investigate the urinary sFas for diagnosis of transitional cell carcinoma (TCC) of urinary bladder. We examined urinary sFas concentration in 74 controls and 117 cases of TCC, both primary and recurrent disease, by using enzyme-linked immunosorbent assay and compared it with urinary cytology. Urinary sFas concentration was found to be significantly higher in the patient as compared to control group (P < 0.05). An optimal cutoff value of 174.0 pg/mL was proposed. The urinary sFas level was found to have an approximate sensitivity and specificity of 88.03% and 89.19% (P < 0.001), whereas urine cytology had sensitivity of 66.67% and specificity of 95.95%. sFas had better sensitivity in higher grade and both primary and recurrent cases of urinary bladder cancer in comparison with cytology. Out of 15 node positive bladder cancer cases, 13 had high urinary sFas levels, whereas 12 were urinary cytology positive for malignancy. Urinary sFas can be used as a non-invasive diagnostic biomarker for TCC of urinary bladder, both for primary and recurrent disease.

Expression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) in human urinary bladder transitional cell carcinoma

The objective of this study was to evaluate the expression pattern of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) and its clinical significance in human bladder cancer (BC).We detected PBK/TOPK mRNA overexpression in BC and human normal testis tissues using RT-PCR. Using qRT-PCR revealed a higher expression of PBK/TOPK in BC tissues than their adjacent noncancerous tissues (ANCTs) (p<0.0001). Cytoplasmic expression of PBK/TOPK protein was found to be positive in 64.6% (42 of 65) BC patients. Expression of PBK/TOPK protein was found to be significantly higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC) (86.1% vs. 37.9%, p<0.001). The immunohistochemical (IHC) expression of PBK/TOPK was found to be significantly (p<0.001) associated with the stage of disease.Study findings suggest that the PBK/TOPK mRNA/protein expression is specific to human BC and might be used as a novel target for development of cancer immunotherapy and diagnostic biomarker.

Trends of adult primary malignant renal tumors over six years

To assess the demographic and clinico-pathological trends, as well as the management options of adult patients with primary malignant renal tumors over 6 years. From July 2003 - July 2009, 55 adult patients with primary malignant renal tumors were treated in two teaching hospitals (Jordan University Hospital in Amman - Jordan and Al-Jumhory Teaching Hospital in Mosul - Iraq). Their data were reviewed retrospectively. Of the 55 patients, 44 had renal cell carcinoma (RCC), eight patients had Transitional cell carcinoma (TCC) of the renal pelvis, two had Sarcoma and one Patient had primary renal lymphoma. Among patients with RCC: the mean age was 56 years, male to female ratio was 3:1. The most common presenting symptom was hematuria. Most of the patients were treated with radical nephrectomy, the clear cell subtype was predominant and most of the patients were diagnosed at stage T2. Regarding patients with TCC: mean age was 57 years, all were treated with radical nephro-ureterectomy and removal of bladder cuff, however (50%) of them developed TCC of urinary bladder within 12 months of radical nephro-ureterectomy. In our series of patients with RCC: there is a trend toward younger age at Diagnosis. We still encountered locally advanced and metastatic disease with a lower rate of incidentally Diagnosed tumors.With regard to patients with renal pelvis TCC: there are trends toward younger age affection, localized disease and early development of bladder TCC which indicate the importance of strict surveillance protocol.

Cyclooxygenase-2 Expression in Urinary Bladder Transitional Cell Carcinoma and its Association with Clinicopathological Characteristics

Transitional cell carcinoma (TCC) is the most predominant type of urinary bladder tumor. As cyclooxygenase (COX)-2 is recently introduced as an attractive target molecule in bladder TCC, we evaluated the immunohistochemical expression of this marker and its association with several clinicopathological characteristics. This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Ninety-two paraffin embedded blocks were selected from patients with urinary bladder TCC who underwent cystectomy or transurethral resection (TUR). Then, we assessed COX-2 expression by immunohistochemical staining using antibody against COX-2. Staining in more than 5% of tumor cells was considered as positive expression. COX-2 was expressed in 50 % of our patients. This marker was markedly expressed in high grade bladder TCC (62.1%) versus other grades and there was statistically a significant difference in COX-2 expression between various grades (p=0.008). In addition, patients' age, lymphatic and perineurial invasion were associated with the expression of COX-2 (p=0.001, 0.015 and 0.039, respectively). However, other parameters such as stage, tumor size, venous invasion and lymph node metastasis did not show any significant relationship with this marker (all, p>0.05). COX-2 was expressed in urinary bladder TCC especially in high grade forms, advocating its probable role in the differentiation of this tumor. Accordingly, COX-2 could be a valuable biological target molecule in the evaluation and treatment of patients with bladder TCC.

Metronomic administration of chlorambucil for treatment of dogs with urinary bladder transitional cell carcinoma

To determine the antitumor effects and toxicoses of metronomic oral administration of a low dose of chlorambucil in dogs with transitional cell carcinoma (TCC). Prospective clinical trial. 31 client-owned dogs with TCC for which prior treatments had failed or owners had declined other treatments. Procedures-Chlorambucil (4 mg/m2, PO, q 24 h) was administered to dogs. Before and at scheduled times during treatment, evaluations of dogs included physical examination, CBC, serum biochemical analyses, urinalysis, thoracic and abdominal imaging including cystosonography for measurement of TCCs, and grading of toxicoses. 29 of 31 dogs had failed prior TCC treatment. Of the 30 dogs with available data, 1 (3%) had partial remission (≥ 50% reduction in tumor volume), 20 (67%) had stable disease (< 50% change in tumor volume), and 9 (30%) had progressive disease (≥ 50% increase in tumor volume or development of additional tumors); 1 dog was lost to follow-up. The median progression-free interval (time from the start of chlorambucil treatment to the day progressive disease was detected) for the dogs was 119 days (range, 7 to 728 days). The median survival time of dogs from the time of the start of chlorambucil treatment was 221 days (range, 7 to 747 days). Few toxicoses were detected; chlorambucil administration was discontinued because of toxicoses in only 1 dog. Metronomic administration of chlorambucil was well tolerated, and 70% of dogs had partial remission or stable disease. Metronomic administration of chlorambucil may be a treatment option for dogs with TCC.

Intraluminal urethral brachytherapy for recurrence of transitional cell carcinoma of urinary bladder in urethral stump

We report a unique case of successfully performed intraluminal brachytherapy for low volume urethral mucosal recurrence of transitional cell carcinoma urinary bladder, initially treated by transurethral resection of bladder tumor, followed by radical cystectomy. Since the patient was unwilling to undergo any other operational interventions, intraluminal brachytherapy of urethra was attempted. Fluroscopy guided intraluminal HDR brachytherapy using Lumencath® catheter under local anesthesia, and remote afterloading system (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden) was performed. A fraction dose of 7 Gy in seven weekly fractions was prescribed at 0.5 cm from the single applicator. The result was promising in terms of local control and symptomatic relief. Therefore, intraluminal brachytherapy in low volume superficial local disease in urethra may play a potential role, and should be applied when repeated surgery is not feasible due to technical or medical reasons.

89-P

Aim The clinical behavior of the human urinary bladder papillary transitional cell carcinoma (TCC) probably results from a complex interaction between carcinogenic insults and host resistance during the patient’s life. While the main recognized risk factor is smoking, little information exists about the susceptibility to TCC development. The human leukocyte antigen E (HLA-E) molecule plays an important role both as a modulator of natural killer (NK) cell activity by interacting with CD94-NKG2A receptor in the innate immunity pathway and as an antigen-presenting molecule triggering a specific immune response, thus it may influence tumor immune surveillance. The aim of this study was to explore a possible influence of five HLA-E variation sites, one in exon 2 at position 424 (rs1059510), three at exon 3 in the positions 756 (rs1264457), 887 (rs41560815) and 906 (rs41562314) and one in exon 4 at the position 1691 (rs17875370), on the susceptibility to urinary bladder TCC development and progression in Brazilian subjects. Methods These variation sites were evaluated by means of direct sequencing of PCR products using an ABI3100 Genetic Analyzer. On this bases, 105 healthy donors and 73 patients with historical of TCC, both from Ribeirao Preto City, Southeast Brazil, were evaluated for the variation sites described above. Results Only two of the five variation sites evaluated were polymorphic in an admixed population such as Brazilians, i.e., positions +424 and +756. Considering these, the allele and genotype distributions in patients and controls were very similar and no significant difference was detected, even when patients were compared as a whole or stratified into high and low grade tumor patients. Conclusions In conclusion, although previous associations have been described evolving neighboring genes such as HLA-A and HLA-G, the HLA-G locus seems to be not associated with TCC susceptibility and/or progression to aggressive tumors.

The expression of cyclooxygenase-2 and survivin in urinary bladder transitional cell carcinoma

The expression of cyclooxygenase-2 and survivin in urinary bladder transitional cell carcinoma

Expression of Protein Kinase Cα and the MZF-1 and Elk-1 Transcription Factors in Human Bladder Transitional Cell Carcinoma Cells

In a recent study on hepatocellular carcinoma (HCC), we have shown that the transcription factors Myeloid Zinc Finger-1 (MZF-1) and Ets-like-protein 1 (Elk-1) are significantly related to protein kinase C alpha (PKCα) expression. The purpose of this study was to determine the correlation of the expression of PKCα with the expression of Elk-1 and MZF-1 in various differentiated urinary bladder transitional cell carcinoma (TCC) cell lines: 5637, BFTC905, TSGH8301, HT1376 and HT1197 cells. The malignant potential in the five TCC cell lines was examined by using cell proliferation/migration/invasion assay and the protein and mRNA levels of PKCα, ElK-1 and MZF-1 were examined by Western blot and RT-PCR analysis. The results showed that the rate of cell proliferation in the TSGH8301 cell line was higher than that in other cell lines, while there were obvious signs of cell migration and invasion in 5637, BFTC905 and HT1376 cells, and no sign in TSGH8301 and HT1197 cells. The resulting expression levels of Elk-1 and PKCα were the highest in 5637 cells, but the MZF-1 expression observed in all five cell lines showed no significant difference. To determine whether a correlation exists between PKCα and Elk-1, a shRNA knockout assay was performed and the results showed that the reduction of Elk-1 expression in 5637 cells did not result in the decreased PKCα expression. Therefore, although the findings showed elevated expression of Elk-1 and PKCα in 5637 cells, the regulator of PKCα in bladder cancer cells is yet to be determined.

Genetic Variability in 8q24 Confers Susceptibility to Urothelial Carcinoma of the Upper Urinary Tract and is Linked With Patterns of Disease Aggressiveness at Diagnosis

Upper urinary tract urothelial carcinoma is rare. Evidence shows that it behaves differently from urothelial bladder tumors. A polymorphism located at the T allele of rs9642880 on chromosome 8q24 is linked to an enhanced risk of bladder tumors. We explored the association of this polymorphism with susceptibility to upper urinary tract urothelial carcinoma. We genotyped the constitutional DNA of 261 patients with upper urinary tract urothelial carcinoma and 261 healthy controls matched for age, gender, smoking habit and ethnicity. Polymorphisms at rs9642880 on chromosome 8q24 were determined using the 5' nuclease polymerase chain reaction method with specific primers and probes. Frequencies were compared between cases and controls. Genotypes were in Hardy-Weinberg equilibrium for cases and controls. Mean patient age was 68.7 years. The T/T genotype resulted in a significantly higher risk of upper urinary tract urothelial carcinoma (OR 1.72, 95% CI 1.1-2.8, p = 0.028). Using single polytomous regression analysis the T/T genotype was also associated with aggressive tumors when stratified by stage (p = 0.003), or grade G2 (p = 0.04) or G3 (p = 0.01). Our results strongly suggest that the T/T rs9642880 genotype is a risk factor for upper urinary tract urothelial carcinoma, as previously shown for bladder tumors. In contrast to bladder carcinoma, for upper urinary tract urothelial carcinoma the T/T genotype is associated with aggressiveness.

Protein expression and gene promoter hypermethylation of CD99 in transitional cell carcinoma of urinary bladder

To investigate the significance of CD99 protein expression and gene promoter hypermethylation status in urinary bladder carcinoma and its correlation with the histopathologic parameters. CD99 protein expression was determined by immunohistochemical staining in a series of 100 cases of transitional cell carcinomas (TCC) and 35 cases of normal urinary bladder tissues, and the methylation status of CD99 gene promoter was studied by using methylation-specific PCR and DNA sequencing. The positive rate of CD99 protein expression was 62% (62/100) in TCC tissues, it was lower than in normal urinary bladder epithelia (97.1%, 34/35). Gene promoter hypermethylation of CD99 was observed in 26 of 82 (31.7%) cases, and none of the detected ten cases of normal transitional epithelia tissues showed CD99 methylation. CD99 hypermethylation was significantly associated with CD99 protein down-regulation in TCC (P < 0.001). Both the decreased protein expression and the higher methylated frequency of CD99 in TCC of urinary bladder were significantly correlated with the clinical stage, pathological stage, and histological grade. The down-regulation of CD99 protein expression is a critical event in the progress of TCC, especially in advanced stage, and it can be explained by the presence of CD99 gene promoter hypermethylation in TCC. And both CD99 protein expression and gene promoter hypermethylation have clinical significance and implication for the diagnosis and target therapy for TCC.