Morphologic and genomic characterization of urothelial to sarcomatoid transition in muscle-invasive bladder cancer

Genitsch, Vera; Kollár, Attila; Vandekerkhove, Gillian; Blarer, Jennifer; Furrer, Marc A.; Annala, Matti; Herberts, Cameron; Pycha, Armin; Jong, Joep J. de; Liu, Yang; Krentel, Friedemann; Davicioni, Elai; Gibb, Ewan A.; Julio, Marianna Kruithof-de; Wyatt, Alexander W.; Seiler, Roland

doi:10.1016/j.urolonc.2019.09.025

Cited by 38 publications

(18 citation statements)

References 41 publications

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“…Of utmost importance, these molecular classes have been established based on investigations of mainly untreated tumor samples. However, the molecular classification has some limitations given the fact that BLCa is a very heterogeneous disease exhibiting vast histological and molecular intra-and inter-tumor heterogeneity was shown in some tumors [160,161]. Consequently, the existence of multiple subtypes within the same tumor has been demonstrated.…”

Section: Limitations and Perspectives Of Molecular Classificationmentioning

confidence: 99%

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Minoli

Kiener

Thalmann

et al. 2020

IJMS

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Bladder cancer is a heterogeneous disease that is not depicted by current classification systems. It was originally classified into non-muscle invasive and muscle invasive. However, clinically and genetically variable tumors are summarized within both classes. A definition of three groups may better account for the divergence in prognosis and probably also choice of treatment. The first group represents mostly non-invasive tumors that reoccur but do not progress. Contrarily, the second group represent non-muscle invasive tumors that likely progress to the third group, the muscle invasive tumors. High throughput tumor profiling improved our understanding of the biology of bladder cancer. It allows the identification of molecular subtypes, at least three for non-muscle invasive bladder cancer (Class I, Class II and Class III) and six for muscle-invasive bladder cancer (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous and neuroendocrine-like) with distinct clinical and molecular phenotypes. Molecular subtypes can be potentially used to predict the response to treatment (e.g., neoadjuvant chemotherapy and immune checkpoint inhibitors). Moreover, they may allow to characterize the evolution of bladder cancer through different pathways. However, to move towards precision medicine, the understanding of the biological meaning of these molecular subtypes and differences in the composition of cell subpopulations will be mandatory.

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Section: Limitations and Perspectives Of Molecular Classificationmentioning

confidence: 99%

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Minoli

Kiener

Thalmann

et al. 2020

IJMS

Self Cite

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“…These opposing results were explained by the relocation of P-cadherin, because patients—where this protein concentrates in the cytoplasm—exhibited a shorter cancer-specific survival (CSS) rate than those where the expression of P-cadherin was circumscribed to the cell membrane. Other work related to the cadherin-switch of basal cells was published by Genitsch, V. et al with a cohort of 21 MIBC patients [ 139 ]. They identified a shift between the molecular subtypes at the transcriptome level, and evidence of active EMT from urothelial toward a sarcomatoid morphology by analyzing the expression of E-cadherin, Zeb1, and TWIST1.…”

Section: Insights Into the Histopathology Of Bladder Cancer By Proteomicsmentioning

confidence: 99%

Proteomics as a Complementary Technique to Characterize Bladder Cancer

López-Cortés

Vázquez‐Estévez

Fernandez

et al. 2021

Cancers

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Bladder cancer (BC) is the most common tumor of the urinary tract and is conventionally classified as either non-muscle invasive or muscle invasive. In addition, histological variants exist, as organized by the WHO-2016 classification. However, innovations in next-generation sequencing have led to molecular classifications of BC. These innovations have also allowed for the tracing of major tumorigenic pathways and, therefore, are positioned as strong supporters of precision medicine. In parallel, immunohistochemistry is still the clinical reference to discriminate histological layers and to stage BC. Key contributions have been made to enlarge the panel of protein immunomarkers. Moreover, the analysis of proteins in liquid biopsy has also provided potential markers. Notwithstanding, their clinical adoption is still low, with very few approved tests. In this context, mass spectrometry-based proteomics has remained a step behind; hence, we aimed to develop them in the community. Herein, the authors introduce the epidemiology and the conventional classifications to review the molecular classification of BC, highlighting the contributions of proteomics. Then, the advances in mass spectrometry techniques focusing on maintaining the integrity of the biological structures are presented, a milestone for the emergence of histoproteomics. Within this field, the review then discusses selected proteins for the comprehension of the pathophysiological mechanisms of BC. Finally, because there is still insufficient knowledge, this review considers proteomics as an important source for the development of BC therapies.

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“…It expresses hallmark epithelial markers, but at the same time demonstrates high-grade spindle cell morphology. Sarcomatoid urothelial carcinoma expresses mesenchymal markers such as ZEB1 and TWIST1 that indicate that it has undergone epithelial-to-mesenchymal transition, which is a potential pathogenic mechanism of sarcomatoid differentiation ( 12 ). Carcinosarcoma is a separate entity on the spectrum between urothelial carcinoma and true sarcoma ( 13 ).…”

Section: Diagnostic Implicationsmentioning

confidence: 99%

“…The other major advance that could improve differentiation between histologic variants is the clinical adoption of artificial intelligence (AI). A recent paper demonstrates that AI can be used to distinguish the molecular subtypes of bladder cancer ( 12 ). AI is dependent on a large sample size and it will require cooperation of the bladder cancer research community to assemble enough cases with variant histology to be able to use this technology moving forward.…”

Section: Diagnostic Implicationsmentioning

confidence: 99%

Variant histology in bladder cancer: diagnostic and clinical implications

Black¹,

Black²

2020

Transl Cancer Res TCR

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Urothelial carcinoma differentiates into variant histological subtypes in approximately 25% of cases. Since every histological variant has unique characteristics, including metastatic potential, expression of immunotherapy targets, and susceptibility to radiation or chemotherapy, every variant offers a unique diagnostic and therapeutic challenge. However, since any single variant is relatively rare, there is a risk of missed pathological diagnosis and sub-optimal clinical management. Ensuring awareness among pathologists and wide-spread familiarity with the nuances of variants among urologists is therefore essential.Additionally, variant histologies may act as an intermediate between classical clinicopathological staging of bladder cancer and evolving molecular classification. Therefore, this review aims to provide a brief overview of the diagnostic, prognostic, and therapeutic implications of each variant histologic subtype.Despite the development of standardized diagnostic criteria, the diagnosis of variant histologies continues to pose a challenge and results in significant interobserver variability. The prognosis of any single variant is poorly studied. However, squamous and glandular differentiation are thought to have little effect on prognosis while micropapillary, sarcomatoid, plasmacytoid, and small cell carcinomas are associated with a poor prognosis. Although evidence surrounding therapeutic strategies is sparse, management guidelines have been developed for variant histologies, which are often treated more aggressively than pure urothelial carcinoma. For example, the presence of variant histology warrants radical cystectomy in patients with T1 disease. Recommendations surrounding neo-adjuvant chemotherapy and radiation therapy also differ with each variant. As new treatments emerge for advanced bladder cancer, studying outcomes in each variant will become critical. Since prognosis and management hinge on the presence of variant histologies, accurate diagnosis and a thorough understanding of these variants are imperative for optimal management of urothelial carcinoma.

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Morphologic and genomic characterization of urothelial to sarcomatoid transition in muscle-invasive bladder cancer

Cited by 38 publications

References 41 publications

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Proteomics as a Complementary Technique to Characterize Bladder Cancer

Variant histology in bladder cancer: diagnostic and clinical implications

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