Loss of <scp>MTAP</scp> expression is strongly linked to homozygous 9p21 deletion, unfavorable tumor phenotype, and noninflamed microenvironment in urothelial bladder cancer

Homozygous 9p21 deletions usually result in a complete loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression visualizable by immunohistochemistry (IHC). MTAP deficiency has been proposed as a marker for predicting targeted treatment response. A tissue microarray including 2,710 urothelial bladder carcinomas were analyzed for 9p21 deletion by fluorescence in situ hybridization and MTAP expression by IHC. Data were compared with data on tumor phenotype, patient survival, intratumoral lymphocyte subsets, and PD-L1 expression. The 9p21 deletion rate increased from pTaG2 low (9.2% homozygous, 25.8% heterozygous) to pTaG2 high (32.6%, 20.9%; p < 0.0001) but was slightly lower in pTaG3 (16.7%, 16.7%) tumors. In pT2-4 carcinomas, 23.3% homozygous and 17.9% heterozygous deletions were found, and deletions were tied to advanced pT (p = 0.0014) and poor overall survival (p = 0.0461). Complete MTAP loss was seen in 98.4% of homozygous deleted while only 1.6% of MTAP negative tumors had retained 9p21 copies (p < 0.0001). MTAP loss was linked to advanced stage and poor overall survival in pT2-4 carcinomas (p < 0.05 each). The relationship between 9p21 deletions/MTAP loss and poor patient prognosis was independent of pT and pN (p < 0.05 each). The 9p21 deletions were associated with a noninflamed microenvironment (p < 0.05). Complete MTAP loss is strongly tied to homozygous 9p21 deletion, aggressive disease, and noninflamed microenvironment. Drugs targeting MTAP-deficiency may be useful in urothelial bladder carcinoma. MTAP IHC is a near perfect surrogate for MTAP deficiency in this tumor type.

Authors

Institutions

Publication Details

Journal
The Journal of Pathology Clinical Research
Published
2024-12-12
DOI
https://doi.org/10.1002/2056-4538.70012
Citations
9
Primary Topic
Bladder and Urothelial Cancer Treatments
Type
article
Field-Weighted Citation Impact
5.15

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Loss of MTAP expression is strongly linked to homozygous 9p21 deletion, unfavorable tumor phenotype, and noninflamed microenvironment in urothelial bladder cancer

Lukas Bubendorf, Niclas C. Blessin, Maximilian Lennartz, Guido Sauter et al.
9 citations
The Journal of Pathology Clinical Research
Bladder and Urothelial Cancer Treatments
5.15
article

Loss of MTAP expression is strongly linked to homozygous 9p21 deletion, unfavorable tumor phenotype, and noninflamed microenvironment in urothelial bladder cancer

Lukas Bubendorf, Niclas C. Blessin, Maximilian Lennartz, Guido Sauter, Krystian Kaczmarek, Tobias Klatte, Henrik Samtleben, Nico Adamini, Sebastian Hofbauer, Natalia Gorbokon, Paul Giacomo Bruch, Michael Rink, Sarah Weinberger, Kira Furlano, Simon Schallenberg, Sarah Jane Pauline Minner, Stefan Koch, Sefer Elezkurtaj, David Horst, Marcin Słojewski, Thorsten Ecke, Henning Plage, Henrik Zecha, Florian Roßner, Ronald Simon, Martina Kluth, Viktoria Ahlburg, Andreas Holger Marx, Margit Fisch, Thorsten Schlomm, Niklas Wößner
article en
9 citations

Abstract

Homozygous 9p21 deletions usually result in a complete loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression visualizable by immunohistochemistry (IHC). MTAP deficiency has been proposed as a marker for predicting targeted treatment response. A tissue microarray including 2,710 urothelial bladder carcinomas were analyzed for 9p21 deletion by fluorescence in situ hybridization and MTAP expression by IHC. Data were compared with data on tumor phenotype, patient survival, intratumoral lymphocyte subsets, and PD-L1 expression. The 9p21 deletion rate increased from pTaG2 low (9.2% homozygous, 25.8% heterozygous) to pTaG2 high (32.6%, 20.9%; p < 0.0001) but was slightly lower in pTaG3 (16.7%, 16.7%) tumors. In pT2-4 carcinomas, 23.3% homozygous and 17.9% heterozygous deletions were found, and deletions were tied to advanced pT (p = 0.0014) and poor overall survival (p = 0.0461). Complete MTAP loss was seen in 98.4% of homozygous deleted while only 1.6% of MTAP negative tumors had retained 9p21 copies (p < 0.0001). MTAP loss was linked to advanced stage and poor overall survival in pT2-4 carcinomas (p < 0.05 each). The relationship between 9p21 deletions/MTAP loss and poor patient prognosis was independent of pT and pN (p < 0.05 each). The 9p21 deletions were associated with a noninflamed microenvironment (p < 0.05). Complete MTAP loss is strongly tied to homozygous 9p21 deletion, aggressive disease, and noninflamed microenvironment. Drugs targeting MTAP-deficiency may be useful in urothelial bladder carcinoma. MTAP IHC is a near perfect surrogate for MTAP deficiency in this tumor type.

The Journal of Pathology Clinical ResearchVol. 11(1)
Universität Hamburg (DE), University Hospital of Basel (CH), University Medical Center Hamburg-Eppendorf (DE), Helios Hospital Bad Saarow (DE), Albertinen Diakoniewerk (DE), Klinikum Fulda (DE), Charité - Universitätsmedizin Berlin (DE), Pomeranian Medical University (PL)
Deutsche Gesellschaft für Urologie
No poverty
Openalex Percentile: Top 4%
Bladder and Urothelial Cancer Treatments
5.15
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.