The Prognostic Importance of E-cadherin and p53 Gene Expression in Transitional Bladder Carcinoma Patients

Arısan, Serdar; Caskurlu, Turhan; Güney, Soner; Nurettin, Sonmez; Bayram, Keles; Damla, Buyuktuncer Elif; Ergenekon, Erbil

doi:10.1007/s11255-005-0919-4

Cited by 12 publications

(9 citation statements)

References 23 publications

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“…Among E-CAD mRNA negative patients, 2 were pTa (2 G3), 3 pT1 G3, 1 pT2 G3, 9 pT3 G3 and 2 pT4 G3. These findings are in line with data from the literature (12,13,24). All samples of normal-appearing mucosa distant from superficial bladder tumors were positive on E-CAD analysis, while among the 14 invasive tumors, 11 were negative and 3 were positive.…”

Section: Molecular Findingssupporting

confidence: 91%

E-cadherin mRNA expression analysis in evaluating the natural history of urothelial bladder cell carcinoma: Results from a long-term follow-up study

Cai

Piazzini²,

Nesi³

et al. 2007

Oncol Rep

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Abstract. Many studies have indicated that the E-cadherin (E-CAD) expression loss is associated with the loss of cellular differentiation and increased cellular invasiveness and can be correlated with poor prognosis in urothelial carcinoma (UC) of the urinary bladder. The aim of this study was to define the role of E-CAD mRNA expression on recurrence, progression and survival in UC of the urinary bladder over a long follow-up period. From 30 patients with bladder UC, enrolled in our previous study, 27 were selected for this study. All patients were re-analyzed in terms of clinical and tumor characteristics, tumor pathological analysis and tumor E-CAD mRNA expression. The data were correlated to 12-year follow-up results. Significant correlations between stage (p=0.002), grade (p=0.008) and E-CAD mRNA expression were reported. E-CAD did not show any correlation in predicting recurrence or progression in bladder UC. The survival analysis demonstrated a significant relationship (p=0.019) between patients with expressed E-CAD mRNA levels and cancer-specific survival. Multivariate analysis demonstrated that expression of E-CAD mRNA levels is an independent prognostic factor in terms of cancerspecific survival in UC of the urinary bladder (p=0.002). Our study is the first to demonstrate that mRNA extraction and Northen blot analysis is to be considered a reliable method to evaluate E-CAD mRNA levels for predicting survival rate in patients affected by urothelial bladder cancers. We stress that a long follow-up period is needed to evaluate the role of molecular factors in predicting prognosis in patients affected by bladder UC.

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Section: Molecular Findingssupporting

confidence: 91%

E-cadherin mRNA expression analysis in evaluating the natural history of urothelial bladder cell carcinoma: Results from a long-term follow-up study

Cai

Piazzini²,

Nesi³

et al. 2007

Oncol Rep

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“…p53 expression showed no correlation with recurrence rate after BCG treatment in none of the studies [18–33]. Although higher protein expression seems to be associated with reduced time to recurrence [23, 34, 35] or progression [18, 19, 23, 26, 32, 34], but this association could not be demonstrated by several other authors (Table 1) [22, 24–26, 28, 30, 31]. Only Saint et al (2004) [23] and Lee (1997) [35] found that p53 could be an independent prognostic factor, but with opposite results.…”

Section: Resultsmentioning

confidence: 91%

Predictive Biomarkers of Bacillus Calmette-Guérin Immunotherapy Response in Bladder Cancer: Where Are We Now?

Lima

Dinis-Ribeiro

Longatto‐Filho

et al. 2012

Advances in Urology

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The most effective therapeutic option for managing nonmuscle invasive bladder cancer (NMIBC), over the last 30 years, consists of intravesical instillations with the attenuated strain Bacillus Calmette-Guérin (the BCG vaccine). This has been performed as an adjuvant therapeutic to transurethral resection of bladder tumour (TURBT) and mostly directed towards patients with high-grade tumours, T1 tumours, and in situ carcinomas. However, from 20% to 40% of the patients do not respond and frequently present tumour progression. Since BCG effectiveness is unpredictable, it is important to find consistent biomarkers that can aid either in the prediction of the outcome and/or side effects development. Accordingly, we conducted a systematic critical review to identify the most preeminent predictive molecular markers associated with BCG response. To the best of our knowledge, this is the first review exclusively focusing on predictive biomarkers for BCG treatment outcome. Using a specific query, 1324 abstracts were gathered, then inclusion/exclusion criteria were applied, and finally 87 manuscripts were included. Several molecules, including CD68 and genetic polymorphisms, have been identified as promising surrogate biomarkers. Combinatory analysis of the candidate predictive markers is a crucial step to create a predictive profile of treatment response.

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“…Most studies have associated tissue E-cadherin expression loss with UC recurrence/progression. [47][48][49][50][51][52][53][54][55][56][57][58][59][60] A higher plasma sE-cad level has been associated with bladder cancer in comparison with healthy controls; a higher preoperative plasma sEcad level has been associated with nodal metastases and shorter PFS in patients treated with radical cystectomy. 61 Our findings are exploratory, and the role of sE-cad in UC merits further investigation.…”

Section: Discussionmentioning

confidence: 99%

A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma

Hussain

Daignault

Agarwal

et al. 2014

Cancer

104

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BACKGROUND Epidermal growth factor receptor overexpression is associated with poor outcomes in urothelial carcinoma (UC). Cetuximab (CTX) exhibited an antitumor effect in in vivo UC models. The efficacy of gemcitabine/cisplatin (GC) with or without CTX in patients with advanced UC was evaluated. METHODS Patients with advanced UC, measurable disease, and adequate organ function were randomized 1:2 to cisplatin (70 mg/m2) on day 1 plus gemcitabine (1000 mg/m2) on days 1, 8, and 15 (arm A) or GC plus CTX (500 mg/m2) on days 1 and 15 (arm B). The primary endpoint was the overall response rate. The secondary endpoints were the response duration, safety, progression-free survival, overall survival, determination of whether or not CTX sensitized nonresponders to GC, and exploratory biomarker analysis. The accrual targets were 27 and 54 patients for the 2 arms, respectively. The overall response rate was reported by arm with binomial confidence intervals (CIs). Kaplan-Meier methods were used for time-to-event endpoints. RESULTS Eighty-eight eligible patients were randomized; 87 were toxicity-evaluable, and 85 were response-evaluable. The overall response rates were 57.1% for arm A (95% CI = 37%–76%) and 61.4% for arm B (95% CI = 48%–74%). The median progression-free survival times were 8.5 months for arm A (95% CI = 5.7–10.4 months) and 7.6 months for arm B (95% CI = 6.1–8.7 months). The median overall survival times were 17.4 months for arm A (95% CI = 12.8 months to unreached) and 14.3 months for arm B (95% CI = 11.6–22.2 months). The most common grade 3/grade 4 adverse events in both arms were myelosuppression and nausea. Thromboembolism, acneiform rash, fatigue, pain, hypersensitivity reactions, elevated transaminases, hyponatremia, and hypomagnesemia were more common in arm B; 3 grade 5 adverse events occurred in arm B. The presence of primary disease significantly correlated with thromboembolism. An increased soluble E-cadherin level after cycle 2 correlated with a higher risk of death. CONCLUSIONS GC plus CTX was feasible but was associated with more adverse events and no improvements in outcomes.

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The Prognostic Importance of E-cadherin and p53 Gene Expression in Transitional Bladder Carcinoma Patients

Cited by 12 publications

References 23 publications

E-cadherin mRNA expression analysis in evaluating the natural history of urothelial bladder cell carcinoma: Results from a long-term follow-up study

E-cadherin mRNA expression analysis in evaluating the natural history of urothelial bladder cell carcinoma: Results from a long-term follow-up study

Predictive Biomarkers of Bacillus Calmette-Guérin Immunotherapy Response in Bladder Cancer: Where Are We Now?

A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma

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