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

Autor:	Gorbokon N; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Wößner N; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Ahlburg V; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Plage H; Department of Urology, Charité Berlin, Berlin, Germany., Hofbauer S; Department of Urology, Charité Berlin, Berlin, Germany., Furlano K; Department of Urology, Charité Berlin, Berlin, Germany., Weinberger S; Department of Urology, Charité Berlin, Berlin, Germany., Bruch PG; Department of Urology, Charité Berlin, Berlin, Germany., Schallenberg S; Institute of Pathology, Charité Berlin, Berlin, Germany., Roßner F; Institute of Pathology, Charité Berlin, Berlin, Germany., Elezkurtaj S; Institute of Pathology, Charité Berlin, Berlin, Germany., Lennartz M; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Blessin NC; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Marx AH; Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany., Samtleben H; Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany., Fisch M; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Rink M; Department of Urology, Marienhospital Hamburg, Hamburg, Germany., Slojewski M; Department of Urology and Urological Oncology, Pomeranian Medical University, Szczecin, Poland., Kaczmarek K; Department of Urology and Urological Oncology, Pomeranian Medical University, Szczecin, Poland., Ecke T; Department of Urology, Helios Hospital Bad Saarow, Bad Saarow, Germany., Klatte T; Department of Urology, Helios Hospital Bad Saarow, Bad Saarow, Germany., Koch S; Department of Pathology, Helios Hospital Bad Saarow, Bad Saarow, Germany., Adamini N; Department of Urology, Albertinen Hospital, Hamburg, Germany., Minner S; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Simon R; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sauter G; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Zecha H; Department of Urology, Charité Berlin, Berlin, Germany.; Department of Urology, Albertinen Hospital, Hamburg, Germany., Horst D; Institute of Pathology, Charité Berlin, Berlin, Germany., Schlomm T; Department of Urology, Charité Berlin, Berlin, Germany., Bubendorf L; Institute of Pathology, University Hospital Basel, Basel, Switzerland., Kluth M; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	The journal of pathology. Clinical research [J Pathol Clin Res] 2025 Jan; Vol. 11 (1), pp. e70012.
DOI:	10.1002/2056-4538.70012
Abstrakt:	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. (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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