Evidence map›Paper›PMID 39327852›Full record

ArticleHistopathology2025

MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle-invasive bladder cancer.

Ekaterina Olkhov-Mitsel, Alexander Oberc, Kenneth J Craddock, Christopher Sherman, Elzbieta Slodkowska, Michelle R Downes

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Article in Histopathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Ekaterina Olkhov-MitselDivision of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.ORCID https://orcid.org/0000-0001-7945-7801
Alexander ObercDivision of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.ORCID https://orcid.org/0000-0001-5024-7974
Kenneth J CraddockDivision of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.ORCID https://orcid.org/0000-0001-9702-0830
Christopher ShermanDivision of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Elzbieta SlodkowskaDivision of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Michelle R DownesDivision of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.ORCID https://orcid.org/0000-0002-4528-3724

Funding

Laboratory Medicine and Molecular Diagnostics Strategic Innovation Fund
6 · The paper itself

Abstract

aimsLoss of heterozygosity in chromosome 9p21, common in urothelial carcinoma (UC), typically involves deletion of CDKN2A and MTAP genes. MTAP loss is emerging as a promising therapeutic target and predictive biomarker in UC. This single-centrre retrospective study examined the incidence of CDKN2A deletions and MTAP loss in muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma (mUC), investigating their correlations with clinical, pathological, and genomic features, as well as patient outcomes.

methodsFluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on 302 MIBC specimens and 63 biopsy-proven metachronous urothelial metastases to assess CDKN2A deletions and MTAP protein expression.

resultsCDKN2A homozygous deletion (HD), identified in 30.3% of MIBCs, and MTAP loss, found in 28.8% of MIBCs, were both significantly associated with the luminal-URO subtype, FGFR3 mutations, and normal/wildtype p53 IHC (P < 0.05). Loss of MTAP expression was significantly correlated with CDKN2A HD, with 84.0% sensitivity, 92.3% negative predictive value (NPV), 96.3% specificity, and 91.9% positive predictive value (PPV). MTAP expression was 100% concordant between primary tumours and nodal metastases. Patients with MTAP loss had a higher incidence of visceral metastases (50%) compared to bone/soft tissue (35.7%) and nodes (14.3%). Mean progression-free survival and overall survival were shorter for patients with MTAP loss, although not statistically significant.

conclusionOur findings highlight CDKN2A HD and MTAP loss as prevalent genetic alterations in MIBC and mUC, particularly within the luminal-URO subtype and FGFR3-mutated, p53-normal/wildtype tumours. MTAP IHC can serve as a surrogate marker for 9p21.3 HD, highlighting its clinical relevance and potential as a therapeutic target and predictive biomarker in MIBC.

Indexed as

Biomarkers, TumorCyclin-Dependent Kinase Inhibitor p16In Situ Hybridization, FluorescenceUrinary Bladder NeoplasmsAdultAgedAged, 80 and overCarcinoma, Transitional CellFemaleHumansImmunohistochemistryLoss of HeterozygosityMaleMiddle AgedPurine-Nucleoside PhosphorylaseRetrospective Studies5'-methylthioadenosine phosphorylaseBiomarkers, TumorCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16Purine-Nucleoside Phosphorylase9p21 lossCDKN2A deletionsmetastatic urothelial carcinomamolecular subtypingMTAP lossmuscle‐invasive bladder cancerp16prognostic biomarkerstherapeutic targets

Identifiers

PMID39327852
PMCPMC11707494

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.