Keywords: Bladder cancer, molecular classifi cation, personalized therapy


This review analyzes the current view on molecular subtypes of muscle-invasive bladder cancer (MI-BC), its key biomarkers, and recommended treatment approaches. Several variants of molecular classifications of BC are known, including the classification of Baylor College of Medicine (BCM), the University of North Carolina (UNC), the MD Anderson Cancer Center (MDA), the Atlas Cancer Genome Project (TCGA), and Lund (Sweden). Nowadays, a consensus international classification of MI-BC has been developed, which not only deepened understanding of the biology of the BC but also showed the relationship of certain genomic disorders with specific morphological subtypes, as well as the clinical pass of the BC. The developed variants of molecular classifications of MI-BC allow not only to predict the course of the tumour process but also stratify patients according to the likely response to chemotherapy and immunotherapy. However, the implementation of molecular classification of MI-BC into clinical practice has several limitations and requires validation studies


Download data is not yet available.


Adam RM, DeGraff DJ. Molecular mechanisms of squamous differentiation in urothelial cell carcinoma: A paradigm for molecular subtyping of urothelial cell carcinoma of the bladder. Urol Oncol. 2015:33 (10): 444-50. PMid:26254697

Aine M, Eriksson P, Liedber F, Sjödahl G, Höglund M. Biological determinants of bladder cancer gene expression subtypes. Sci Rep. 2015; 5: 10957. PMid:26051783 PMCid:PMC4650643

Aine M, Eriksson P, Liedberg F, Höglund M, Sjödahl G. On Molecular Classification of Bladder Cancer: Out of One, Many. Eur. Urol. 2015; 68: 921-923.doi: 10.1016 / j.eururo.2015.07.021. PMid:26215606

Bernardo C, Eriksson P, Marzouka N, Liedberg F, Sjödahl G, Höglund M. Molecular pathology of the luminal class of urothelial tumors J Pathol. 2019; 249 (3): 308-318. doi: 10.1002 / path.5318. PMid:31232464 PMCid:PMC6851980

Biton A, Bernard-Pierrot I, Lou Y, Krucker C, Chapeaublanc E, Rubio-Pérez C. et al. Independent analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes. Cell Rep. 2014; 9 (4): 1235-1245. PMid:25456126

Chan KS, Espinosa I, Chao M, Wong D, Ailles L, Diehn M. et al. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci USA 2009 року; 106 (33): 14016-14021. PMid:19666525 PMCid:PMC2720852

Choi W, Czerniak B, Ochoa A, Su X, Siefker-Radtke A, Dinney C, McConkey DJ. Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer. Nat Rev Urol. 2014; 11 (7): 400-410. PMid:24960601

Choi W, Porten S, Kim SS, Willis D, Plimack ER, Hoffman-Censits J. et al. Identification of Distinct Basal and Luminal Subtypes of Muscle-Invasive Bladder Cancer with Different Sensitivities to Frontline Chemotherapy. Cancer Cell. 2014; 25: 152-165. PMid:24525232 PMCid:PMC4011497

Damrauer JS, Hoadley KA, Chism DD, Fan C, Tiganelli CJ, Wobker SE. et al. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci USA. 2014; 111: 3110-3115. PMid:24520177 PMCid:PMC3939870

Eriksson P, Aine M, Veerla V, Liedberg F, Sjödahl G, Höglund M. Molecular subtypes of urothelial carcinoma are defined by specific gene regulatory systems. BMC Medical Genomics 2015; 8: 25. PMid:26008846 PMCid:PMC4446831

Fishwick C, Higgins J, Percival-Alwyn L, Hustler A, Pearson J, Bastkowski S. et al. Heterarchy of transcription factors driving basal and luminal cell phenotypes in human urothelium. Cell Death Differ. 2017: 24: 809-818. PMid:28282036 PMCid:PMC5423105

Hedegaard J, Lamy P, Nordentoft I. Comprehensive transcriptional analysis of early-stage urothelial carcinoma. Cancer Cell. 2016 року; 30: 27-42. PMid:27321955

Ho PL, Kurtova A, Chan KS. Normal and neoplastic urothelial stem cells: Getting to the root of the problem. Nat Rev Urol. 2012; 9 (10): 583-594. PMid:22890301 PMCid:PMC3468664

Hurst CD, Alder O, Platt FM. Genomic subtypes of non-invasive bladder cancer with distinct metabolic profile and female gender bias in KDM6A mutation frequency. Cancer Cell. 2017; 32: 701-15. PMid:29136510 PMCid:PMC5774674

Hurst CD, Platt FM, Taylor CF, Knowles MA. Novel tumor subgroups of urothelial carcinoma of the bladder defined by integrated genomic analysis. Clin Cancer Res. 2012; 18: 5865-5877. PMid:22932667 PMCid:PMC5081094

Kamoun A, de Reyniès A, Allory Y, Sjödahl G, Robertson AG, Seiler R et al. A consensus molecular classification of muscle-invasive bladder cancer European urology. 2019:pii: S0302-2838 (19) 30695-5.

Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer. 2015; 15: 25-41. PMid:25533674

Lerner SP, McConkey DJ, Hoadley KA. et al. Bladder cancer molecular taxonomy: summary from a consensus meeting. Bladder Cancer. 2016; 2: 37-47. PMid:27376123 PMCid:PMC4927916

Lindgren D, Sjödahl G, Lauss M, Staaf J, Chebil G, Lövgren K. et al. Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma. PLoS One. 2012; 7 (6): e38863. PMid:22685613 PMCid:PMC3369837

McConkey DJ, Choi W, Dinney CP. New insights into subtypes of invasive bladder cancer: Considerations of the clinician. Eur Urol. 2014; 66 (4): 609-610. PMid:24877661

McConkey DJ, Choi W. Molecular Subtypes of Bladder Cancer. Curr Oncol Rep. 2018; 20 (10): 77. PMid:30128829

Mo Q, Nikolos F, Chen F, Tramel Z, Lee YC, Hayashi K. et al. Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial Carcinomas. J. Natl. Cancer Inst. 2018; 110 (5): 448-459. PMid:29342309 PMCid:PMC6279371

Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G. et al. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cell. 2017; 171: 540-556.e25.doi: 10.1016 / j.cell.2018.07.036.

Satyal U, Sikder RK, McConkey D, Plimack ER, Abbosh PH. Clinical implications of molecular subtyping in bladder cancer Curr Opin Urol. 2019; 29 (4): 350-356. PMid:31158107

Sjödahl G, Eriksson P, Liedberg F, Höglund M. Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification. J Pathol. 2017; 242 (1): 113-125. PMid:28195647 PMCid:PMC5413843

Sjödahl G, Lauss M, Lovgren K, Chebil G, Gudjonsson S, Veerla S. et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res. 2012; 18 (12): 3377-3386. PMid:22553347

Sjödahl G, Lövgren K, Lauss M, Patschan O, Gudjonsson S, Chebil G. et al. Toward a molecular pathologic classification of urothelial carcinoma. Am J Pathol. 2013; 183 (3): 681-691. PMid:23827819

Sjödahl G. Molecular Subtype Profiling of Urothelial Carcinoma Using a Subtype-Specific Immunohistochemistry Panel. Methods Mol Biol. 2018; 1655: 53-64. doi: 10.1007 / 978-1-4939-7234-0_5.

Song D, Powles T, Shi L., Lirong Z, Ingersoll MA, Lu YL. Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches J Pathol. 2019; 249 (2): 151-165. PMid:31102277 PMCid:PMC6790662

Sulaieva ON, Stakhovskiy OE, Shapochka DO Molecular pathology of urothelial carcinoma: prognostic and predictive biomarkers. Practical oncology. 2019; 2 (4): 29-40.

Tan TZ, Rouanne, M., Tan, KT, Huang, RY-J., And Thiery, J.-P. Molecular Subtypes of Urothelial Bladder Cancer: Results from a Meta-cohort Analysis of 2411 Tumors. Eur. Urol. 2019; 75: 423-432. PMid:30213523

Thomsen MBH, Nordentoft I, Lamy P, Vang S, Reinert L, Mapendano CK. et al. Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer. Sci. Rep. 2017; 7, 11702.doi: 10.1038 / s41598-017-11291-0.

Volkmer JP, Sahoo D, Chin RK, Ho PL, Tang C, Kurtova AV. et al. Three differentiation states risk-stratify bladder cancer into distinct subtypes. Proc Natl Acad Sci USA 2012; 109 (6): 2078-2083. doi: 10.1073 / pnas.1120605109.

Warrick JI, Sjödahl G, Kaag M, Raman JD, Merrill S, Shuman L et al. Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants. Eur. Urol. 2019; 75 (1): 18-22. PMid:30266310

Weinstein J, Akbani R, Broom B. et al. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507: 315-322 doi: 10.1038 / nature12965. PMid:24476821 PMCid:PMC3962515

Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W. et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 2013; 4: 2612. PMid:24113773 PMCid:PMC3826632

Abstract views: 92
PDF Downloads: 4
How to Cite
Sulaieva O, Seleznov O, Shapochka D, Ponomarchuk R, Stakhovsky O, Stefiniv N. MOLECULAR SUBTYPES OF MUSCULAR INVASIVE BLADDER CANCER. Proc Shevchenko Sci Soc Med Sci [Internet]. 2020Apr.14 [cited 2020Jun.5];59(1). Available from: