Prognosis Of Transitional Cell Carcinoma Research Articles

Biochemical study of E-Cadherin and SATB1 in Urothelial Bladder Carcinoma of Egyptian Patients

Bladder cancer was considered the third most common tumor in Egypt according to the National Cancer Institute (NCI) registry. However, Transitional cell carcinoma of the urinary bladder represents about 90% of all bladder cancer cases. Method; The aim of the study was to evaluate the expression levels (mRNA and protein) of E-cadherin and special AT-rich sequence binding protein-1 (SATB1) as biomarkers for transitional cell carcinoma (TCC) using immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR) techniques of the Egyptian urinary bladder patients compared to the noncancerous bladder tissues. The study included 48 TCC tissues (41 males and 7 females) of different grades and stages and 12 noncancerous bladder tissues (7 males and 5 females). Results; A statistically significant association regarding smoking and gender were found between the bladder transitional cell carcinoma (BTCC) group and the control group. However, there was no statistically significant difference in comparing the presence of schistosomiasis in both studied groups. The expression of E-cadherin was significantly down expressed and SATB1 was significantly over expressed in TCC tissues compared to the noncancerous bladder tissues at both mRNA and protein levels. Decreased expression of E-cadherin and over expression of SATB1 were statistically associated with tumor stage, tumor grade, and tumor size. On the other hand, no statistically significant difference was detected between the expressions of the two studied genes and either gender or age. A significant association was found between the protein expressions of E-cadherin and SATB1. Pearson correlation test showed significantly negative correlation between mRNA expressions of E-cadherin and SATB1. Conclusion; E-cadherin and SATB1 expressions may be considered as good biochemical markers for the diagnosis and prognosis of transitional cell carcinoma in urinary bladder of Egyptian patients.

Increased expression of POLR3G predicts poor prognosis in transitional cell carcinoma.

BackgroundPrevious studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC.MethodsThe RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC.ResultsTranscriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT.ConclusionsPOLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.

Evaluation of androgen receptor and HER2/neu receptor in tumor tissue of transitional cell carcinoma of urinary bladder and normal bladder mucosa

Background: Transitional cell carcinoma (TCC) is the most prevalent, singly accounting for 90% of all bladder cancer cases. Various markers involved in cell cycle but none of them proven its capacity as a prognostic indicator. The discovery of new biological markers may lead to early clinical prediction and may help in individualization of therapeutic approach in management of bladder cancer patients. The human epidermal growth factor receptors (EGFRs) – HER2/neu play a role in neoplastic cell growth and its role proven in breast and ovarian cancer while its role in bladder cancer still not explored its potential. Bladder cancer incidence is higher in male as compared to female. This gender related difference is still not clear in humans while it is proven in animal studies. In this study, we investigated the potential role and association of HER2/neu and androgen receptors (ARs) in etiology and prognosis of TCC. Patients and Methods: The study included 20 histopathologically confirmed cases of TCC of urinary bladder attending the Department of General Surgery, KGMU, Lucknow and 20 healthy individuals were taken as control. Immunohistochemical analysis for AR and HER2/neu receptor was done using paraffin-embedded tissue blocks treated with monoclonal mouse anti-human antibodies against AR and HER2/neu receptor, respectively. Results: HER2/neu over expression was observed in 14 (73%) of which 12 were males and 2 were females. Among these 16.7%, 33.3%, and 37.5% cases were in Grade I, II, and III, respectively. The AR overexpression was observed in 4 (20%) of which all were males. About 16.7% and 27.3% cases were in Grade II and III, respectively. Peak incidence was observed in the age group of 50–70 years (75%). Conclusions: We conclude that HER2/neu and AR can be considered as bad prognostic factor in TCC. These results suggested that targeting AR and HER2/neu may provide novel chemopreventive and therapeutic approaches for the management of bladder cancer.

Impact of p53, MIB-1 and PECAM-1 expression on the prognosis of urothelial carcinoma of the renal pelvis

ObjectiveDetermining whether the overexpression of p53, MIB-1 and PECAM-1 of protein levels is of interest in predicting the prognosis of transitional cell carcinoma of the upper urinary tract (TCC-UUT) with the primary seat in the renal pelvis. Materials and methodsA univariate and multivariate analysis was conducted for prognosis prediction in a series of 82 patients with TCC-UUT of the renal pelvis who had no metastases at diagnosis (N0/Nx M0) and were treated exclusively with nephroureterectomy. We assessed clinicopathological parameters (age, gender, tumor grade and extent, histological variety, growth pattern, vascular invasion, infiltration of the renal parenchyma, and tumor necrosis) and the immunohistochemical expression of p53, MIB-1 (ki-67) and PECAM-1 (CD31) in sections performed with tissue microarray (TMA). ResultsA total of 47.6% of the patients had high-grade lesions according to the USIP-WHO classification. The growth pattern was flat in 15.85%. The distribution by T category was: 3.7% pTa, 51.2% pT1, 11% pT2, 29.3% pT3 and 4.9% pT4. The mean follow-up was 46.8±38.5 (range 4–172) months. The median survival was reached at 57 (95% CI 44–63) months. The univariate analysis revealed that survival in these patients is associated with tumor size (p=.028), histological variety (p<.0001), growth pattern (p<.0001), grade (p<.0001), pT (p=.01), vascular invasion (p=.025), necrosis (p=.004) and overexpression of p53 (p=.0006), PECAM-1 (p=.0036) and MIB-1 (p=.0038). The Cox regression model showed that high-grade (HR, 4.2; 95% CI 1.28–13.79; p=.018), flat-growth pattern (HR, 2.52; 95% CI 1.05–6.03; p=.038) and p53 overexpression (HR, 2.8; 95% CI 1.22–6.44; p=.015) were independent predictors. ConclusionHistological grade, tumor growth pattern and p53 overexpression were established as the primary predictors of prognosis for primary TCC-UUT of the renal pelvis. The independent value of MIB-1 observed in other studies was not reproduced in this study.

Impacto de la expresión de p53, MIB-1 y PECAM-1 en el pronóstico del carcinoma urotelial de la pelvis renal

ObjectiveDetermine whether the overexpression p53, MIB-1 and PECAM-1 of protein levels is of interest in predicting the prognosis of transitional cell carcinoma of the upper urinary tract (TCC-UUT) with the primary seat in the renal pelvis. Material and methodA univariate and multivariate analysis was conducted for prognosis prediction in a series of 82 patients with TCC-UUT of the renal pelvis who had no metastases at diagnosis (N0/Nx M0) and were treated exclusively with nephroureterectomy. We assessed clinicopathological parameters (age, gender, tumor grade and extent, histological variety, growth pattern, vascular invasion, infiltration of the renal parenchyma, tumor necrosis) and the immunohistochemical expression of p53, MIB-1 (ki-67) and PECAM-1 (CD31) in sections performed with tissue microarray (TMA). ResultsA total of 47.6% of the patients had high-grade lesions according to the USIP-WHO classification. The growth pattern was flat in 15.85%. The distribution by T category was: 3.7% pTa, 51.2% pT1, 11% pT2, 29.3% pT3 and 4.9% pT4. The mean follow-up was 46.8+38.5 (range, 4-172) months. The median survival was reached at 57 (95% CI 44-63) months. The univariate analysis revealed that survival in these patients is associated with tumor size (P=.028), histological variety (P<.0001), growth pattern (P<.0001), grade (P<.0001), pT (P=.01), vascular invasion (P=.025), necrosis (P=.004) and overexpression of p53 (P=.0006), PECAM-1 (P=.0036) and MIB-1 (P=.0038). The Cox regression model showed that high-grade (HR, 4.2; 95% CI 1.28-13.79; P=.018), flat growth pattern (HR, 2.52; 95% CI 1.05-6.03; P=.038) and p53 overexpression (HR, 2.8; 95% CI 1.22-6.44; P=.015) were independent predictors. ConclusionHistological grade, tumor growth pattern and p53 overexpression were established as the primary predictors of prognosis for primary TCC-UUT of the renal pelvis. The independent value of MIB-1 observed in other studies was not reproduced in this study.

The interrelationships between Src, Cav-1 and RhoGD12 in transitional cell carcinoma of the bladder

Background:The aim of this current study was to assess the expression and activity of Src family kinases, focal adhesion kinase (FAK), caveolin (Cav-1) and RhoGD12 in bladder cancer.Methods:Fifty-eight patients with a new diagnosis of bladder cancer undergoing transurethral resection were included. Immunohistochemical staining was utilised to assess expression of c-Src, dephosphorylated (SrcY530), phosphorylated Src (Y419), phosphorylated FAK (FAK Y861), Cav-1 and RhoGD12. Expression was assessed using the weighted histoscore method.Results:High expression of dephosphorylated Y527, phosphorylated Y416 and phosphorylated FAK Y861 in the membrane were associated with increased cancer-specific survival (P=0. 01, P=0.001, P=0.008, respectively) and expression of Y416 in the membrane was an independent factor on multivariate analysis when combined with known clinical parameters (P=0.008, HR 0.288, 95% CI 0.11–0.72).Conclusion:These results demonstrate that in contrast to other solid tumours, activation of the Src family members and downstream signalling proteins are associated with a good prognosis in transitional cell carcinoma of the bladder, and activated Src has a positive relationship with RhoGD12.

Identification of genes correlated with early-stage bladder cancer progression.

Transitional cell carcinoma (TCC) of the bladder ranks fourth in incidence of all cancers in the developed world, yet the mechanisms of its origin and progression remain poorly understood. There are also few useful diagnostic or prognostic biomarkers for this disease. We have combined a transgenic mouse model for invasive bladder cancer (UPII-SV40Tag mice) with DNA microarray technology to determine molecular mechanisms involved in early TCC development and to identify new biomarkers for detection, diagnosis, and prognosis of TCC. We have identified genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild-type littermates at 3, 6, 20, and 30 weeks of age. These are ages that correspond to premalignant, carcinoma in situ, and early-stage and later stage invasive TCC, respectively. Our preliminary analysis of the microarray data sets has revealed approximately 1,900 unique genes differentially expressed (> or =3-fold difference at one or more time points) between wild-type and UPII-SV40Tag urothelium during the time course of tumor development. Among these, there were a high proportion of cell cycle regulatory genes and a proliferation signaling genes that are more strongly expressed in the UPII-SV40Tag bladder urothelium. We show that several of the genes upregulated in UPII-SV40Tag urothelium, including RacGAP1, PCNA, and Hmmr, are expressed at high levels in superficial bladder TCC patient samples. These findings provide insight into the earliest events in the development of bladder TCC as well as identify several promising early-stage biomarkers.

Expression and clinical significance of survivin in transitional cell carcinoma of bladder

Objective To investigate the expression and clinical significance of survivin in tran-sitional cell carcinoma (TCC) of bladder. Methods Forty-six cases with defined pathologic grades and clinical stages were analyzed retrospectively. Fluorescence quantitative real-time polymerse chain reaction was used to detect the survivin mRNA levels of all the samples including 28 tumor lateral nor-mal tissues as the control group. Results Forty cases (87.0%) with TCC of the bladder showed positive survivin signals, however the control group showed negative signals. There was significant difference of survivin mRNA expression in single focus and multiple focuses tumors. The similar sta-tistical result was obtained in new patients and relapsed cases. The differences between clinical stages were also significant. However, the expression of survivin mRNA was not correlated with pathologic grades. Conclusions The up-regulated expression of survivin is significantly correlated with clinical stages, relapsed and multiple focuses tumors. Survivin seems to be a promising marker for analyzing clinical stages and predicting the prognosis of TCC. Key words: Bladder neoplasms; Transitional cell carcinoma; Survivin

The Protective Role of Renal Parenchyma as a Barrier to Local Tumor Spread of Upper Tract Transitional Cell Carcinoma and its Impact on Patient Survival

We investigated whether tumor location has independent prognostic significance in upper tract transitional cell carcinoma cases and which factor determines it. We reviewed data on 122 renal pelvis and 102 ureteral tumor cases, including the recurrence pattern. Tumor location and other clinicopathological variables were evaluated regarding cancer specific and recurrence-free survival. Stage pT3 tumors were stratified into those invading renal parenchyma or peripelvic/periureteral fat. Overall 5-year cancer specific survival and recurrence-free survival rates were 77.0% and 71.6%, respectively, at a mean followup of 60.7 months. Of the clinicopathological parameters T stage was the most significant prognosticator of the survival rate, while nodal involvement, high grade and ureteral tumor location were also significant for lower survival rates. Stratification analysis for matching pathological stage revealed that, while survival rates were similar in the renal pelvis and ureteral tumor groups at stage pT2 or less, renal pelvic tumors were associated with significantly higher survival rates than ureteral tumors for stage pT3. Specifically renal pelvic tumors invading the renal parenchyma were associated with a lower local failure rate, and higher cancer specific and recurrence-free survival rates than tumors invading peripelvic or periureteral fat, ie 77.5% vs 49.7% 5-year cancer specific survival and 75.6% vs 32.0% 5-year recurrence-free survival (p = 0.014 and 0.003, respectively). Tumor location is an independent prognostic factor for pT3 upper tract transitional cell carcinoma. The overall better prognosis of renal pelvic tumors was mainly attributable to pT3 tumor outcomes, specifically lesions invading the renal parenchyma. These findings may be due to the protective role of thick renal parenchyma against local tumor spread.

The Prognostic Predictors of Primary Ureteral Transitional Cell Carcinoma After Radical Nephroureterectomy

We studied the long-term prognosis, and evaluated the predictors of disease specific and recurrence-free survival in a large cohort of patients who had undergone radical nephroureterectomy for primary transitional cell carcinoma of the ureter. From January 1990 to December 2006, 145 patients with primary ureteral transitional cell carcinoma treated with nephroureterectomy and bladder cuff removal at our institution were included in the study. The medical records of these patients were reviewed retrospectively. The clinical and histopathological data were analyzed to evaluate the prognostic predictive factors. Univariate and multivariate statistical analyses were performed. The 5-year disease specific survival rates of stage pTa/Tis/T1, pT2, pT3 and pT4 were 94.6%, 81.8%, 47.4% and 0%, respectively. The 5-year recurrence-free survival rates according to tumor grade were 68.4% for low grade and 35.7% for high grade disease. Of the 145 patients subsequent bladder tumors developed in 38 (26.2%), local recurrence developed in 11 (7.6%) and metachronous contralateral upper urinary tract tumor developed in 3 (2.1%). Most patients had subsequent tumor recurrence within the first year after radical surgery. On univariate and multivariate analyses tumor stage, tumor grade, severity of chronic renal disease, synchronous bladder tumor and hematuria were the significant prognostic variables predicting disease specific and recurrence-free survival. Advanced tumor and chronic renal disease stages were significantly associated with a worse prognosis in patients with primary ureteral transitional cell carcinoma who had undergone radical nephroureterectomy. With regard to tumor recurrence, advanced tumor stage, high tumor grade and synchronous bladder tumor were independent risk factors.

The Role of Lymphovascular Invasion in Predicting the Prognosis of Clinically Localized Upper Tract Urothelial Carcinoma (pT1-3cN0M0)

We assessed the impact of lymphovascular invasion on the prognosis of patients treated for clinically localized (pT1-3N0M0) upper tract urothelial carcinoma. From January 1998 to December 2004, 106 patients treated surgically for clinically localized upper tract urothelial carcinoma (pT1-3cN0M0) were recruited for analysis retrospectively. We assessed the impact of multiple prognostic factors including age, sex, smoking, tumor multiplicity, pathological stage, grading, squamous differentiation, subsequent bladder tumor recurrence, tumor site and lymphovascular invasion on the recurrence-free survival rate. We clarified the role of lymphovascular invasion in predicting cancer specific survival in these patients. Mean patient age was 67.2 +/- 11.1 years and median followup was 47.5 months (range 40 to 115). Lymphovascular invasion was present in 32 of 106 (30.2%) patients. The 5-year recurrence-free survival rate in patients with and without lymphovascular invasion was 65.3% and 91.9%, respectively (p <0.001). On multivariate analysis lymphovascular invasion status, pT3 and ureteral involvement were significant predictors of patient recurrence-free survival. The positivity of lymphovascular invasion was also significantly associated with the risk of higher stage disease (OR 7.49). Patients with lymphovascular invasion had a higher risk of greater pathological stage disease. Lymphovascular invasion and high stage disease with ureteral involvement led to a greater risk of disease recurrence and, in turn, recurrence caused a higher mortality rate. This finding could help identify patients at greater risk for disease recurrence who would benefit from close followup and early adjuvant therapy.

Impact of Caveolin-1 Expression on the Prognosis of Transitional Cell Carcinoma of the Upper Urinary Tract

This study aimed to investigate the relationship of caveolin-1 expression with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT). Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 98 patients, who had undergone radical nephroureterectomy, were stained immunohistochemically using antibodies against caveolin-1. The expression pattern of caveolin-1 was compared with the clinicopathological variables. The caveolin-1 expression was significantly correlated with T stage (p<0.001) and grade (p=0.036). The survival rate of patients with caveolin-1 positive tumors was significantly lower than that of patients with caveolin-1 negative tumors (p<0.0001). The univariate analyses identified T stage, grade, and caveolin-1 expression as significant prognostic factors for cancer-specific survival, whereas the multivariate analyses indicated that T stage and caveolin-1 expression were independent prognostic factors. These results show that the increased expression of caveolin-1 is associated with tumor progression and poor prognosis in TCC-UUT, suggesting that caveolin-1 may play an important role in the progression of TCC-UUT.

The Impact Factors on Prognosis of Patients With pT3 Upper Urinary Tract Transitional Cell Carcinoma

Stage 3 upper urinary tract transitional cell carcinoma is a heterogeneous disease including different tumor locations (pelvis vs ureter) and invasion patterns (renal parenchyma, peripelvic fat and periureteral fat). Unfortunately the outcomes of patients with pT3 disease with different invasion pattern are largely unknown. This study presents the clinical outcome of patients with pT3 disease with upper urinary tract transitional cell carcinoma. We retrospectively reviewed the medical records of all patients with pT3 disease with upper urinary tract transitional cell carcinoma. Four patient groups were classified according to tumor location and tumor invasion pattern. Prognostic factors including age, gender, tumor grade, tumor size, tumor number, tumor location and microscopic finding of vascular invasion were analyzed with respect to disease recurrence and survival. A total of 72 patients were included in this study. The most common complaint and tumor relapse pattern were painless gross hematuria and distant metastasis, respectively. Patients with pT3 disease with superficial parenchymal invasion had better disease-free and recurrence-free survival than the other 3 groups. Initial tumor location (p = 0.02) and vascular invasion (p = 0.02) were independent factors for disease-free survival, and vascular invasion (p = 0.001) was the only predictive factor for recurrence-free survival. The present study demonstrated that patients with pT3 disease with superficial parenchymal invasion should be considered to have lower stage disease, and that vascular involvement is the only independent prognostic factor for patients with pT3 disease for disease-free and recurrence-free survival. Systemic adjuvant therapy should be recommended for patients with pT3 disease with vascular involvement.

Prognosis of Transitional Cell Carcinoma of the Bladder in Patients 40 Years Old or Less: Comparison with Elderly Patients

Purpose: The natural history and prognosis of transitional cell carcinoma (TCC) of the bladder in young patients remain a matter of debate. This study aimed to evaluate whether TCC of the bladder in young patients is biologically different from that found in elderly patients. Materials and Methods: The medical records of 21 patients presenting with TCC of the bladder at 40 years of age and younger (group 1) were reviewed and compared with those of 94 patients who were diagnosed with bladder TCC at 51 years of age and older (group 2). Results: The initial stage distribution was similar with 85.7% and 79.8% of patients presenting with superficial TCC in group 1 and 2, respectively. The gross hematuria as a presenting symptom, multiplicity of tumor mass, T stage, N stage, M stage, concomitant carcinoma in situ (CIS) and grade were not significantly different between the two groups. There was no difference in the cancer-specific survival rate between the two groups. For the cases with superficial TCC, no difference was observed in the diseasefree survival rate or progression-free survival rate between the two groups. Conclusions: TCC of the bladder in patients 40 years old or less has a similar clinicopathological distribution and disease outcome to those observed in elderly patients. It is suggested that the management and follow-up of TCC of the bladder in young patients should be the same

Downregulation of Survivin Is Associated With Reductions in TNF Receptors' mRNA and Protein and Alterations in Nuclear Factor Kappa B Signaling in Urothelial Cancer Cells

Because survivin is selectively expressed in and associated with an unfavorable prognosis in transitional cell carcinoma of the bladder (TCC), we treated T-24 cells with survivin siRNA. Survivin siRNA treatment caused a profound decrease of survivin protein that was associated with decreased cell growth, a specific G2/M arrest and increased cytochrome c release. Microarray analysis of apoptosis genes showed that levels of 14/114 gene products were decreased after 72 hours treatment with survivin siRNA, including survivin, three TNF receptors, Akt, c-Abl, caspases and their related genes and Bcl-2 and NF-κB signaling related genes. TNFR1, pro-caspase-2 and Akt protein levels were decreased after survivin siRNA treatment for 48 and 72 hours. Downregulation of survivin causes changes in mitosis and apoptosis, which may be related to changes in TNF receptors and NF-κB signaling.

Correlation of Cyclooxygenase-2 Expression and Microvessel Density with Prognosis in Transitional Cell Carcinoma of the Upper Urinary Tract

Purpose: The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 expression and microvessel density (MVD), a reflection of angiogenesis, with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT). Materials and Methods: Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 91 patients, who had undergone radical nephroureterectomy, were examined immunohistochemically using antibodies against COX-2 and CD34. MVD was determined with CD34-stained slides. The expression patterns of COX-2 and MVD were compared with the clinicopathological variables. Results: The COX-2 expression was significantly correlated with T stage (p=0.002), N stage (p=0.010), and grade (p=0.027). MVD was also significantly correlated with T stage (p<0.001), N stage (p=0.002), and grade (p=0.001). The COX-2 expression was significantly correlated with MVD (p=0.001). The survival rate of patients with COX-2 positive tumors or high MVD was significantly lower than that of patients with COX-2 negative tumors or low MVD, respectively (p=0.0013, p=0.0312). Univariate analyses identified T stage, N stage, grade, COX-2 expression, and MVD as significant prognostic factors for cancer-specific survival; multivariate analyses indicated that T stage was the only independent prognostic factor. Conclusions: The increased expression of COX-2 and MVD is associated with a worse prognosis in TCC-UUT. The COX-2 expression is correlated with MVD. These results suggest that COX-2 may play an important role in the progression of TCC-UUT and angiogenesis may be affected by COX-2 during the progression of TCC-UUT. (Korean J Urol 2007;48: 376-382)

The Prognostic Significance of Elevated Serum Creatinine for the Recurrence and Progression in Superficial Bladder Tumors

Purpose: There are many prognostic indicators of bladder tumors including clinical, pathological and molecular markers based on tumor-related factors. This study was performed to evaluate the significance of an elevated level of serum creatinine for predicting progression and recurrence of superficial bladder tumors. Materials and Methods: One hundred forty-seven patients that initially presented with a superficial bladder tumor (pTa or pT1) except for a carcinoma in situ were retrospectively analyzed according to several factors such as tumor stage, grade, size, multiplicity and serum creatinine for tumor recurrence and progression after a primary transurethral resection. Results: The elevated serum creatinine group consisted of 20 patients 11 patients experienced recurrence (55.0%) and 3 patients experienced progression (15.0%). The control group consisted of 127 patients 39 patients experienced recurrence (30.7%) and 13 patients experienced progression (10.2%). The presence of an elevated level of serum creatinine and tumor multiplicity were statistically significant prognostic factors for tumor recurrence. Conclusions: These results can be helpful for predicting the prognosis of transitional cell carcinoma of the bladder and for planning therapeutic and follow-up strategies. (Korean J Urol 2007;48:927-932)

Prognostic factors for primary superficial transitional cell carcinoma of the bladder: a retrospective cohort study

Previous studies showed that the prognostic factors for superficial transitional cell carcinoma of the bladder varied with the findings of different cohorts. Few multivariate analyses of prognostic factors for superficial bladder tumors have been reported in China and bladder preservation as a prognostic index of superficial bladder tumors is limited and scarce in Chinese patients. This study was conducted to analyze a group of risk factors for prognostic outcomes for patients with primary superficial transitional cell carcinoma of the bladder. Between January 1980 to December 2000, 198 patients [172 men and 26 women; mean age (52.98 +/- 11.28) years] with primary superficial transitional cell carcinoma who were pathologically classified as Ta or T1 in Hunan Provincial Tumor Hospital (Changsha, China) were enrolled in this study. Surgical methods included local resection and electric coagulation of bladder tumors, transurethral resection of bladder tumors and partial cystectomy. After initial surgical treatment, patients were followed through a cystoscopy every three months during the first two years and every six months thereafter in the design of retrospective cohort. Survival analysis was performed to analyze risk factors of the prognostic outcomes for transitional cell carcinoma of the bladder. Canonical correlation analysis was conducted to present and interpret synthetically the multi-correlation between all kinds of prognostic outcomes and risk factor in multiply dimensions. The average follow-up period was (6.65 +/- 4.74) years. Assessments at three, five, and 10 years showed recurrence rates, respectively, of (28.32 +/- 3.45)%, (35.31 +/- 3.83)%, and (42.48 +/- 4.40)%; progression rates of (8.89 +/- 2.14)%, (15.16 +/- 2.94)%, and (23.88 +/- 4.19)%; bladder-preservation rates of (94.68 +/- 1.74)%, (93.87 +/- 1.91)%, and (91.51 +/- 2.49)%; metastasis rates of (8.25 +/- 2.05)%, (11.24 +/- 2.47)%, and (28.94 +/- 4.93)%; and cancer-related survival rates of (95.02 +/- 1.62)%, (90.70 +/- 2.45)%, and (77.14 +/- 4.88)%. The main risk factors for recurrence were histological grade, blood transfusion during surgery and the duration of symptoms. Progression was affected by blood transfusion during surgery, histological grade, the number of re-examinations, and the length of the recurrence-free period. Metastasis was associated with tumor multifocality, hydronephrosis, microscopic growth pattern, and the recurrence-free period. Cancer-related survival was influenced by microscopic growth pattern and the recurrence-free period. Bladder preservation involved only the recurrence-free period. The comprehensive results from canonical correlation analysis showed that the main prognostic outcomes were cancer-related survival, metastasis and progression respectively, while the dominate risk factors were histological grade, tumor multifocality and blood transfusion. The risk factors were different for each prognostic outcome of transitional cell carcinoma of the bladder. This is helpful for predicting the prognosis of transitional cell carcinoma of the bladder and designing therapeutic and follow-up strategies for this cancer.

Relation between Cyclooxygenase-2 Expression and Clinicopathologic Parameters with Patient Prognosis in Transitional Cell Carcinoma of the Bladder

Objective: To evaluate the correlation between cyclooxygenase-2 (Cox-2) expression and clinicopathologic findings with the effect of these variables on prognosis of bladder cancer. Methods: Cox-2 expression was examined immunohistochemically in paraffin blocks of 99 patients. Correlations between Cox-2 expression and variables like cancer stage and grade, number of mitoses, angiolymphatic invasion, number and size of the lesions were determined. Results: Cox-2 expression was detected in 52 (52.5%) patients. Univariate regression analysis between Cox-2 expression and clinicopathologic findings showed a significant correlation only in the pathologic stage of the patients (p = 0.048) (OR =2.64, CI = 0.97–7.81). Multivariate regression analysis in stage T1 revealed an increasing number of mitoses as an independent prognostic factor for recurrence (p = 0.002) (OR = 1.5, CI = 1.16–1.92) and progression (p = 0.030) (OR = 8.23, CI = 1.22–55.27) although a prognostic factor was not found for progression in stage T2. Conclusion: Univariate analysis showed that only the pathologic stage correlated significantly with Cox-2 expression. Cox-2 expression revealed a significant relation with patient prognosis in stage T2 but not in stage T1. These results support the fact that Cox-2 inhibitors may play a role in progression of invasive bladder tumors.

Significance of the Time Period Between Diagnosis of Muscle Invasion and Radical Cystectomy With Regard to the Prognosis of Transitional Cell Carcinoma of the Urothelium in the Bladder

Significance of the Time Period Between Diagnosis of Muscle Invasion and Radical Cystectomy With Regard to the Prognosis of Transitional Cell Carcinoma of the Urothelium in the Bladder