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.2019.06.021

Cited by 23 publications

(8 citation statements)

References 47 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

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“…A recent study by Genitsch et al 28 showed that there is common ancestry between conventional UC and adjacent sarcomatoid areas, and that a loss of E-Cad expression in SUC is consistent with epithelial-to-mesenchymal transition. In our study, E-Cad was lost in 83% of SUC cases.…”

Section: Molecular Results and Correlation With Immunohistochemical Stainingmentioning

confidence: 98%

p-120 Catenin is a Useful Diagnostic Biomarker for Distinguishing Plasmacytoid and Sarcomatoid Variants From Conventional Urothelial Carcinoma

Acosta

Barletta

Sonpavde

et al. 2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Plasmacytoid urothelial carcinoma (PC-UC) is an aggressive variant of urothelial carcinoma (UC), characterized by loss of E-cadherin (E-Cad)–mediated intercellular adhesion. Loss of E-Cad by immunohistochemistry can help diagnosis PC-UC; however, sensitivity is limited. Expression of other cadherin-catenin adhesion complex members, that is, p-120 catenin (p-120) and β-catenin (B-Cat), which are diagnostically useful for lobular breast carcinoma, remains unknown in UC. Objective.— To determine the utility of p-120 and B-Cat in conventional and variant UC. Design.— E-cadherin, B-Cat, and p-120 immunohistochemistry was performed in 25 conventional UCs and 33 variant UCs, including 22 PC-UCs, 6 sarcomatoid UCs (SUCs), and 5 micropapillary UCs. Membranous staining for all biomarkers was considered normal; however, any cytoplasmic staining or an absence of staining was considered diagnostically abnormal. Next-generation sequencing was performed on 8 PC-UC cases. Results.— E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17 of 22; 77%) with an additional 2 of 22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21 of 22 cases (95%). Most SUCs showed an absence of E-Cad (5 of 6; 83%) and cytoplasmic or negative p-120 in 5 of 6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive. Conclusions.— p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC.

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“…3 With the feature of spindled cells, SAV-BC shows an epithelial-tomesenchymal transition from the urothelial to the sarcomatoid morphology. 15 The detection of SAV-BC generally portends a poor prognosis based on a more advanced stage at diagnosis and worse OS. 10 Patients with RHV-BC had a higher proportion of advanced stage and worse prognosis than those with pure bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Clinical Characteristics and Prognosis of Rare Histological Variants of Bladder Cancer: A Single-Center Retrospective Study from China</p>

Li¹,

Li²,

Yang³

et al. 2020

CMAR

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To investigate the clinical characteristics and prognosis of patients with rare histological variants of bladder cancer (RHV-BC) in China. Materials and Methods: Patients diagnosed as bladder carcinoma with RHV in our center, from March 2009 and April 2019, were included. The univariate and multivariate COX regression model were used to evaluate the association between clinical characteristics and overall survival (OS). Results: A total of 54 (1.4%) patients with RVH-BC were identified from 3803 potential patients with bladder cancer. The RHV classifications included micropapillary variant (MPV), sarcomatoid variant (SAV), neuroendocrine variant (NEV), nested variant (NV), plasmacytoid variant (PCV), and lymphoepithelioma-like variant (LEV), which were found in 19, 18, seven, six, three, and one patient, respectively. The mean of recurrence-free survival (RFS), cancer-specific survival (CSS), and OS of patients were 18.8 months, 37.0 months and 36.0 months, respectively. The multivariable analyses indicated that metastasis and T ≥2 were independent risk factors of OS. Besides, 84.4% (27/32) of patients who were receiving intravesical therapies (IVT) suffered recurrence. Patients with adjuvant chemotherapy (AC) had a recurrence rate of 64.7% (11/17). Conclusion: T≥2 and metastasis were independent risk factors of OS in patients with RHV-BC. Considering a high recurrence following transurethral resection of bladder tumor (TURBT) and IVT, early radical cystectomy (RC) might be performed for patients with RHV-BC.

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

Cited by 23 publications

References 47 publications

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

p-120 Catenin is a Useful Diagnostic Biomarker for Distinguishing Plasmacytoid and Sarcomatoid Variants From Conventional Urothelial Carcinoma

<p>Clinical Characteristics and Prognosis of Rare Histological Variants of Bladder Cancer: A Single-Center Retrospective Study from China</p>

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