Bladder cancer: translating molecular genetic insights into clinical practice
- PMID: 21106220
- DOI: 10.1016/j.humpath.2010.07.007
Bladder cancer: translating molecular genetic insights into clinical practice
Abstract
Transitional cell (urothelial) carcinoma of the bladder is the second most common urologic malignancy and is one of the best understood neoplasms, with relatively well-defined pathogenetic pathways, natural history, and tumor biology. Conventional clinical and pathologic parameters are widely used to grade and stage tumors and to predict clinical outcome of transitional cell carcinoma; but the predictive ability of these parameters is limited, and there is a lack of indices that could allow prospective assessment of risk for individual patients. In the last decade, a wide range of candidate biomarkers representing key pathways in carcinogenesis have been reported to be clinically relevant and potentially useful as diagnostic and prognostic molecular markers, and as potential therapeutic targets. The use of molecular markers has facilitated the development of novel and more accurate diagnostic, prognostic, and therapeutic strategies. FGFR3 and TP53 mutations have been recognized as key genetic pathways in the carcinogenesis of transitional cell carcinoma. FGFR3 appears to be the most frequently mutated oncogene in transitional cell carcinoma; its mutation is strongly associated with low tumor grade, early stage, and low recurrence rate, which confer a better overall prognosis. In contrast, TP53 mutations are associated with higher tumor grade, more advanced stage, and more frequent tumor recurrences. These molecular markers offer the potential to characterize individual urothelial neoplasms more completely than is possible by histologic evaluation alone. Areas in which molecular markers may prove valuable include prediction of tumor recurrence, molecular staging of transitional cell carcinoma, detection of lymph node metastasis and circulating cancer cells, identification of therapeutic targets, and prediction of response to therapy. With accumulating molecular knowledge of transitional cell carcinoma, we are closer to the goal of bridging the gap between molecular findings and clinical outcomes. Assessment of key genetic pathways and expression profiles could ultimately establish a set of molecular markers to predict the biological nature of tumors and to establish new standards for molecular tumor grading, classification, and prognostication. The main focus of this review is to discuss clinically relevant biomarkers that might be useful in the management of transitional cell carcinoma and to provide approaches in the analysis of molecular pathways that influence the clinical course of bladder cancer.
Copyright © 2011 Elsevier Inc. All rights reserved.
Similar articles
-
Molecular alterations associated with bladder cancer initiation and progression.Scand J Urol Nephrol Suppl. 2008 Sep;(218):154-65. doi: 10.1080/03008880802291915. Scand J Urol Nephrol Suppl. 2008. PMID: 18815930 Review.
-
Alteration of the vascular endothelial growth factor and angiopoietins-1 and -2 pathways in transitional cell carcinomas of the urinary bladder associated with tumor progression.Anticancer Res. 2004 Sep-Oct;24(5A):2745-56. Anticancer Res. 2004. PMID: 15517881
-
Genetic and epigenetic aspects of bladder cancer.J Cell Biochem. 2005 May 1;95(1):24-33. doi: 10.1002/jcb.20412. J Cell Biochem. 2005. PMID: 15759278 Review.
-
Comparison of the WHO/ISUP classification and cytokeratin 20 expression in predicting the behavior of low-grade papillary urothelial tumors. World/Health Organization/Internattional Society of Urologic Pathology.Mod Pathol. 2001 Apr;14(4):267-72. doi: 10.1038/modpathol.3880300. Mod Pathol. 2001. PMID: 11301341
-
FGFR3 and Tp53 mutations in T1G3 transitional bladder carcinomas: independent distribution and lack of association with prognosis.Clin Cancer Res. 2005 Aug 1;11(15):5444-50. doi: 10.1158/1078-0432.CCR-05-0122. Clin Cancer Res. 2005. PMID: 16061860
Cited by
-
MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the PIK3R2-mediated PI3K/Akt signaling pathway.Onco Targets Ther. 2016 Aug 22;9:5181-93. doi: 10.2147/OTT.S105198. eCollection 2016. Onco Targets Ther. 2016. Retraction in: Onco Targets Ther. 2021 Mar 10;14:1859. doi: 10.2147/OTT.S309735. PMID: 27578985 Free PMC article. Retracted.
-
Tumor heterogeneity in muscle-invasive bladder cancer.Transl Androl Urol. 2020 Dec;9(6):2866-2880. doi: 10.21037/tau.2020.03.13. Transl Androl Urol. 2020. PMID: 33457261 Free PMC article. Review.
-
Prognostic significance of mucin expression in urothelial bladder cancer.Int J Clin Exp Pathol. 2014 Jul 15;7(8):4945-58. eCollection 2014. Int J Clin Exp Pathol. 2014. PMID: 25197366 Free PMC article.
-
An integrated method for the identification of novel genes related to oral cancer.PLoS One. 2017 Apr 6;12(4):e0175185. doi: 10.1371/journal.pone.0175185. eCollection 2017. PLoS One. 2017. PMID: 28384236 Free PMC article.
-
Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.PLoS One. 2015 Jun 5;10(6):e0127908. doi: 10.1371/journal.pone.0127908. eCollection 2015. PLoS One. 2015. PMID: 26046361 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous