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Molecular Testing in Urothelial Tumors

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Book cover Molecular Testing in Cancer

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Abstract

Recent evidence supports the presence of two distinct pathways of urothelial carcinoma. The majority of tumors are superficial noninvasive low-grade tumors which are often multifocal with high recurrence rate and infrequent progression. Muscle-invasive disease, on the other hand, represents 20 % of tumors with approximately 50 % chance of developing metastases. In this chapter, we discuss the molecular pathway involved in the pathogenesis of urothelial carcinoma at the genomic, transcriptomic, proteomic, and epigenetic levels. We also explore the molecular aspects of multifocality, heterogeneity, and tumor recurrence. The recent isolation of cells with cancer stem cell properties can have significant therapeutic implications. We also outline the currently available molecular markers in urothelial carcinoma. These markers can be of great values for screening, early diagnosis, assessment of prognosis, and surveillance for disease recurrence. These include soluble urine markers and cell-based markers. Emerging biomarkers of potential clinical significance include DNA methylation, microRNA analysis, and circulating tumor cells. Molecular profiling or global analysis of molecular changes hold the promise of a better understanding of the mechanisms of aggressive behavior and can lead to new biological, rather than morphological, classification of urothelial tumors. The use of multiparametric approach and the integration of molecular markers with clinical parameters can significantly improve assessment of outcome. Molecular approaches are also the basis to develop new, more effective, targeted therapies in bladder cancer.

Urinary bladder cancer is the fourth most common tumor in North America and the second most common urologic malignancy. Histologically, more than 90 % are urothelial tumors. Molecular studies have shown that urothelial carcinomas (UC) represent a heterogeneous group of tumors that may evolve along two pathways with distinct biological behavior and clinical prognosis, as described below.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University Hospital, 339 Windermere Road, London, ON, Canada, N6A 5A5

    Manal Y. Gabril M.D.

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, 1 King’s College Circle, Toronto, ON, Canada, M5S 1A8

    George M. Yousef M.D., Ph.D.

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  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    George M. Yousef

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Serge Jothy

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Gabril, M.Y., Yousef, G.M. (2014). Molecular Testing in Urothelial Tumors. In: Yousef, G., Jothy, S. (eds) Molecular Testing in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8050-2_18

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