Research Article: Clinical Significance of ErbB Receptor Family in Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis

Date Published: September 9, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Yuh-Shyan Tsai, Hong-Lin Cheng, Tzong-Shin Tzai, Nan-Haw Chow.


The prognostic importance of examining ErbB receptor family expression in human bladder cancer remains uncertain. Using published evidence, we examined the clinical value and the updated results of clinical trials targeting ErbB receptor family members. Twenty-seven articles from 65 references related to ErbB receptor expression assessment in bladder cancer were reviewed. The estimates included the association significance, hazard ratios, and 95% confidence intervals (CIs) from actuarial curves and survival analyses. A meta-analysis was done on those reports using univariate log-rank tests or a Cox-regression model. The methods of analysis and study subjects chosen varied widely among studies. The overall risks of disease progression for patients with EGFR or ErbB2 overexpression were 4.5 (95% CI: 2.5–8.4) and 1.1 (95% CI: 0.6–1.9), and the risks of mortality were 3.0 (95% CI: 1.6–5.9) and 1.1 (95% CI: 1.0–1.2), respectively. However, the significance of coexpression patterns of the ErbB receptor family remains controversial. None of six clinical trials yielded convincing results for blockading ErbB receptor signaling in urothelial carcinoma. The results of this analysis suggest that assessing co-expression patterns of the ErbB family may provide better prognostic information for bladder cancer patients.

Partial Text

One characteristic of bladder cancer is its variable patient prognosis. About 70% of superficial (Ta and T1) tumors recur, and 10–20% of them become invasive [1]. Tumors that are invasive at primary diagnosis carry a high risk of progression despite radical cystectomy and other auxiliary treatments. Conventional prognostic factors, such as tumor stage, grade, size, and multifocality, do not accurately predict the clinical outcome for some patients. Therefore, extensive efforts have been made to identify biomarkers for predicting disease progression, response to treatment, and chance of long-term survival. Currently, it is recommended that patients with bladder cancer have regular urinary cytology, cystoscopy, and imaging studies at followup [2].

This meta-analysis revealed that estimates of the significance of ErbB receptor family member expression vary substantially between studies. Nonetheless, EGFR overexpression is moderately predictive of progression and mortality in patients with bladder cancer. ErbB2 overexpression is weakly predictive of cancer mortality. Since relatively few studies have examined the implications of ErbB3 and ErbB4, no conclusion can be made at this stage. However, these findings should be interpreted carefully because relatively few studies were eligible for analysis.

In conclusion, this meta-analysis has revealed a significant association between ErbB family receptor expression and progression and mortality in patients with bladder cancer even though these findings need to be carefully interpreted. Considering current molecular information, assessing ErbB family coexpression patterns may provide better prognostic information for patients with bladder cancer. Updated clinical trials suggest that more investigations are required to identify effective agents for targeting ErbB signaling of urothelial carcinoma. Systematic reviews and meta-analyses are mandatory before accepting ErbB receptor expression patterns as predictive markers for clinical application.




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