A Consensus Molecular Classification of Muscle-Invasive Bladder Cancer

Kamoun, Aurélie; Reyniès, Aurélien de; Allory, Yves; Sjödahl, Gottfrid; Robertson, A. Gordon; Seiler, Roland; Hoadley, Katherine A.; Al‐Ahmadie, Hikmat; Choi, Woonyoung; Groeneveld, Clarice S.; Castro, Mauro A. A.; Fontugne, Jacqueline; Eriksson, Pontus; Mo, Qianxing; Kardos, Jordan; Zlotta, Alexandre R.; Hartmann, Arndt; Dinney, Colin P.N.; Bellmunt, Joaquim; Powles, Thomas; Malats, Núria; Chan, Keith S.; Kim, William Y.; McConkey, David J.; Black, Peter C.; Dyrskjøt, Lars; Höglund, Mattias; Lerner, Seth P.; Real, Francisco X.; Radvanyi, François

doi:10.2139/ssrn.3372965

Cited by 140 publications

(321 citation statements)

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“…Recent advances in the molecular taxonomy of UC have led to molecular subtypes, with implications for the treatment of each of those subtypes. In the most recent consensus classification system by Kamoun et al, six molecular classes were proposed, among them the luminal papillary class which includes apparently uninflamed tumors with frequent papillary growth patterns and 40% FGFR3 mutations [9]. With an immunohistochemical marker panel limited to six antibodies, we were able to classify LNUC within the luminal subtype of UC regardless of the respective tumor component.…”

Section: Discussionmentioning

confidence: 94%

“…According to our analysis, the majority of LNUCs do not seem to be eligible for immunotherapy. This is supported by the fact that LNUC represents the molecular subtype of luminal papillary bladder cancers, in which FGFR3 alterations are among the most important oncogenic mechanisms [9]. The FGFR3 oncogenic pathway is associated with a non-T-cell-inflamed cancer phenotype, characterized by reduced CD8+ T cells, chemokines, and interferons, resulting in resistance to immune checkpoint inhibitors [20].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, LNUC samples showed an FGFR3 mutation frequency much higher than in conventional MIBC and points to the possibility of an FGFR3-driven scenario in pure LNUC cases. Only three tumors showed additional expression of basal markers, which would be most appropriately classified as "Urobasal B subtype" tumors of the Lund classification [9].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, molecular subtypes of UC based on gene expression analyses are supposed to have predictive value [8]. A molecular taxonomy consensus classification of UC summarizing the results of several gene expression studies revealed six bladder cancer subtypes [9].…”

Section: Introductionmentioning

confidence: 99%

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Pure Large Nested Variant of Urothelial Carcinoma (LNUC) Is the Prototype of an FGFR3 Mutated Aggressive Urothelial Carcinoma with Luminal-Papillary Phenotype

Weyerer

Eckstein

Compérat

et al. 2020

Cancers

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Since 2016, large nested urothelial carcinoma (LNUC) has been included within the WHO classification of urothelial tumors. Limited reports with mainly small case series have confirmed the malignant behavior of LNUC despite its bland morphological appearance. We evaluated, for the first time, markers for new immunooncological or targeted therapies including FGFR3 mutational status and PD-L1 status, the frequency of TERT-promoter mutations and the molecular subtype in a cohort of 25 LNUC using SNaPshot analysis and immunohistochemistry. Of the 25 cases, 17 were pure LNUC, with 13 showing an additional exophytic papillary/papillary-like component. Seven mixed LNUCs presented areas of classical nested variant urothelial carcinoma (NVUC) and one showed a component of conventional urothelial carcinoma. Of the 17 evaluable pure LNUCs, 16 were FGFR3-mutated with identical mutations in their concomitant papillary/papillary-like components. An FGFR3 mutation was found in 1/7 evaluable mixed LNUCs combined with NVUC. TERT-promoter mutations were detected in 86.7% pure and 83.3% mixed tumors. Immunohistochemistry revealed a luminal phenotype; PD-L1 was negative in the majority of tumor cells and tumor-associated immune cells. Pure LNUC is a prime example of a luminal, FGFR3-mutated, mostly PD-L1-negative tumor. In contrast, FGFR3 mutations seem to be rare in mixed LNUC, which may indicate a different pathway of tumor development.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pure Large Nested Variant of Urothelial Carcinoma (LNUC) Is the Prototype of an FGFR3 Mutated Aggressive Urothelial Carcinoma with Luminal-Papillary Phenotype

Weyerer

Eckstein

Compérat

et al. 2020

Cancers

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“…The advent of gene‐expression profiling has broadened our ability to subclassify bladder cancers into molecular classifications based on their gene‐expression profile . As a result, numerous classification systems have been described subtyping urothelial bladder cancer.…”

mentioning

confidence: 99%