Molecular pathology of urothelial carcinoma: prognostic and predictive biomarkers
Keywords:urothelial carcinomas, biomarkers, treatment
AbstractUrothelial carcinomas (UC) accounts for about 90 % of all bladder cancers. Nowadays, the prognosis and treatment of patients with UC is based on clinical, instrumental and histopathological features. However, widely recognized clinical and pathological characteristics are often insufficient for precise prognosis and prediction of therapy efficacy. In this review, we analyzed the molecular mechanisms of UC development and discussed current approaches to UC prognostication and individualized therapy selection using molecular biomarkers. UCs have an extremely complex genetic profile. To date, more than 300 mutations, above 200 copy number variations, and more than 20 rearrangements have been identified in UC. Study of UC biology showed the multifactorial nature of genetic and genomic disorders, both in the tumor cells and in tumor microenvironment. The most challenging task while interpreting molecular alterations is to define the clinical significance of each molecular biomarker in UC. In this review, the authors discuss the role of chromosomal and genetic alterations, including chromosome 9 aberrations, FGFR3, RAS, PI3KCA, TP53 and RB1 mutations, in the pathogenesis of UC development and progression. In addition, the manuscript presents data on prognostic and predictive markers of muscle-invasive UCs, including regulators of proliferation and apoptosis, hypoxia, DNA repair enzymes, as well as immunological biomarkers. A comprehensive study of chromosomal and genetic alterations, the signatures of gene expression and immune checkpoints in combination with clinical, laboratory, instrumental and histopathological data made it possible not only to understand better the nature and significance of various molecular disorders, but also contributed to further development of advanced UC classification based on molecular subtypes with specific treatment recommendations in line with molecular profiling of the tumor.
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