The Lund Molecular Taxonomy Applied to Non–Muscle-Invasive Urothelial Carcinoma

Marzouka, Nour Al Dain; Eriksson, Pontus; Bernardo, Carina; Hurst, Carolyn D.; Knowles, Margaret A.; Sjödahl, Gottfrid; Höglund, Mattias

doi:10.1016/j.jmoldx.2022.05.006

Cited by 17 publications

(41 citation statements)

References 43 publications

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“…The LundTax Mes-like subtype is similar to the consensus stroma-rich subtype; however, the status of these subtypes as specific cancer cell subtypes is still unclear. LundTax differs even more with respect to the two proposed systems for non-muscle-invasive tumors [10,21] because those are highly dependent on signals from infiltrating nontumor cells and cancer cell proliferation, features not considered class-defining properties in the LundTax system [22]. Although LundTax classifies the great majority of non-muscleinvasive tumors as UroA, the Lindskrog approach subdivides UroA into four different classes, mainly determined by proliferation and infiltration levels [10].…”

Section: Discussionmentioning

confidence: 99%

“…Although LundTax classifies the great majority of non-muscleinvasive tumors as UroA, the Lindskrog approach subdivides UroA into four different classes, mainly determined by proliferation and infiltration levels [10]. The LundTax exclusion of infiltration and proliferation signatures as class-defining features does not dismiss the importance of infiltration and proliferation for (clinical) assessment of the tumors; estimates of immune or stromal infiltration, as well as proliferation, can easily be derived from the gene expression profiles as separate variables [22,31]. Moreover, it is a reasonable scientific approach to sort out variables that together produce specific complex outcomes, such as progression, to be able to perform proper analyses.…”

Section: Discussionmentioning

confidence: 99%

“…This finding was validated in two recent large transcriptomic non‐muscle‐invasive cohorts. [22]. In addition, worse prognosis was found for the GU subtype compared to Uro, particularly in BCG (Bacillus Calmette‐Guèrin) untreated patients where the effect size was similar to that of stage T1 compared to Ta (multivariable hazard ratios 6.0 and 6.7, respectively) [25].…”

Section: Progress Toward Clinical Applications Of Lundtaxmentioning

confidence: 99%

“…The RandomForest version was then applied to two large and independent non‐muscle‐invasive (Ta and T1) datasets [10,21]. The correct classification was validated by previously described gene expression signatures as well as by gene mutation and genomic alteration data provided by the two original publications [22]. This shows that the LundTax classification system and the connected algorithms are applicable to both muscle invasive and non‐muscle‐invasive urothelial carcinomas.…”

Section: How To Do ‘Immunohistochemistry’ With More Than 20 Markers U...mentioning

confidence: 99%

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The Lund taxonomy for bladder cancer classification – from gene expression clustering to cancer cell molecular phenotypes, and back again

Höglund

Bernardo

Sjödahl

et al. 2023

The Journal of Pathology

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Treatment of bladder cancer patients depends on precise diagnosis. Molecular subtyping by gene expression profiling may contribute substantially to subclassification of bladder cancer. Several classification systems have been proposed. Most of these base their classification on whole biopsy features, and molecular subtypes are therefore often defined by a combination of features from the cancer cells as well as infiltrating noncancer cells. This makes the link to what is seen at the cancer cell level unclear. The aim of the Lund taxonomy (LundTax) has been to align gene expression‐level classification with immunohistochemical classification to identify cancer cell phenotypes independent of infiltration and proliferation. A systematic approach was used in which gene expression clusters were validated and adjusted by immunohistochemistry using markers expressed only by the cancer cells. This review provides a rationale for defining molecular subtypes and a step‐by‐step description of the development of the LundTax with motivations for each modification and extension. As the cancer cell phenotype defined by gene expression profiling corresponds with the immunohistochemistry of cancer cells, the LundTax represents a harmonization of the gene expression and immunohistochemical levels. Furthermore, the classification system is independent of pathological stage and is, thus, applicable to all urothelial carcinomas. A unified classification system relevant for both the molecular biologist and pathologist will facilitate systematization of current treatment practices, as well as the development of new treatments. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Progress Toward Clinical Applications Of Lundtaxmentioning

confidence: 99%

Section: How To Do ‘Immunohistochemistry’ With More Than 20 Markers U...mentioning

confidence: 99%

See 2 more Smart Citations

The Lund taxonomy for bladder cancer classification – from gene expression clustering to cancer cell molecular phenotypes, and back again

Höglund

Bernardo

Sjödahl

et al. 2023

The Journal of Pathology

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“…Cancer genomics studies have shown that activating mutations in FGFR3 are highly enriched in papillary urothelial carcinomas 3,9 . We further validated these findings in the mouse urothelial transformation assay in independent experiments using a defined LV pool of Fgfr3 S243C, Ywhaz, Pik3ca E545K, Pparg, and Pvrl4 (Extended Data Fig.…”

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confidence: 99%

Combinatorial genetic strategy accelerates the discovery of cancer genotype-phenotype associations

Wong

Sun

et al. 2023

Preprint

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Available genetically-defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Herein, we describe a combinatorial genetic strategy applied to an organoid transformation assay to rapidly generate diverse, clinically relevant bladder and prostate cancer models. Importantly, the clonal architecture of the resultant tumors can be resolved using single-cell or spatially resolved next-generation sequencing to uncover polygenic drivers of cancer phenotypes.

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Molecular classification of urothelial bladder carcinoma

Schwarzova,

Varchulova Novakova,

Danisovic

et al. 2023

Mol Biol Rep

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Urothelial bladder carcinoma (UC) ranks among the top ten most commonly diagnosed cancers worldwide on an annual basis. The standardized classification system for urothelial bladder tumors is the Tumor, Node, Metastasis classification, which reflects differences between non-muscle-invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma (MIBC) and it depends on the extent to which tumor has infiltrated the bladder wall and other tissues and organs. NMIBC and MIBC exhibit great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. In recent years, studies based on mRNA expression profiling revealed the existence of biologically relevant molecular subtypes of UC, which show variant molecular features that can provide more precise stratification of UC patients. Here, we present a complex classification of UC based on mRNA expression studies and molecular subtypes of NMIBC and MIBC in detail with regard to different mRNA expression profiles, mutational signatures, and infiltration by non-tumor cells. The possible impact of molecular subtyping on treatment decisions and patients’ outcomes is outlined, too.

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The Lund Molecular Taxonomy Applied to Non–Muscle-Invasive Urothelial Carcinoma

Cited by 17 publications

References 43 publications

The Lund taxonomy for bladder cancer classification – from gene expression clustering to cancer cell molecular phenotypes, and back again

The Lund taxonomy for bladder cancer classification – from gene expression clustering to cancer cell molecular phenotypes, and back again

Combinatorial genetic strategy accelerates the discovery of cancer genotype-phenotype associations

Molecular classification of urothelial bladder carcinoma

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