Prevalence of S-methyl-5′-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer - A Tissue Microarray Study

Sep 21, 2026

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Loss of S-methyl-5′-thioadenosine phosphorylase (MTAP) expression is a common cancer event that creates a critical therapeutic vulnerability. Homozygous MTAP deletions produce complete loss detectable by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). A tissue microarray with 17,078 samples across 149 tumor entities was analyzed by IHC, showing complete MTAP loss in 83 categories and defining frequent deletion-associated expression loss, with notable exceptions such as neuroendocrine tumors and Hodgkin lymphomas. MTAP deficiency correlates with unfavorable tumor phenotype, PD-L1 expression patterns, and low CD8+ lymphocyte density, and carries substantial diagnostic value for detecting neoplastic transformation.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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Abstract

MTAP deficiency prevalence and detection

Clinical and microenvironment associations

Diagnostic implications

Prevalence of S-methyl-5′-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer A Tissue Microarray Study on 13,067 Tumors From 149 Different Tumor Types Natalia Gorbokon, MD,* Niklas Wößner,* Maximilian Lennartz, MD,* Sebastian Dwertmann Rico, MD,* Simon Kind, MD, * Viktor Reiswich, MD,* Florian Viehweger, MD,* Florian Lutz, MD,* Christoph Fraune, MD,*† Andreas M. Luebke, MD,* Claudia Hube-Magg, PhD,* Anne Menz, MD,*Ria Schlichter, MD,*Till Krech, MD,*† Andrea Hinsch, MD,* Eike Burandt, MD,* Guido Sauter, MD,* Ronald Simon, PhD,* Stefan Steurer, MD,* Andreas H. Marx, MD,*‡ Patrick Lebok, MD,*† David Dum, MD,* Sarah Minner, MD,* Frank Jacobsen, MD,* Till S. Clauditz, MD,* Thilo Hackert, MD,§ Faik G. Uzunoǧlu, MD,§ Lukas Bubendorf, MD,‖ Christian Bernreuther, MD,* and Martina Kluth, PhD* Abstract: Loss of S-methyl-5 ′-thioadenosine phosphorylase (MTAP) expression is a common event in cancer leading to a critical vulnerability of cancer cells towards anti-cancer drugs. Homozygous MTAP deletions result in a complete expression loss that can be detected by immunohistochemistry (IHC) . In this study, a tissue microarray containing 17,078 samples from 149 different tumor entities was analyzed by IHC, and complete MTAP loss was validated by ﬂuorescence in situ hybridization. MTAP loss was observed in 83 of 149 tumor categories, including neuroendocrine neoplasms (up to 80%), Hodgkin lymphoma (50.0%), mesothelioma (32.0% to 36.8%), gastro-intestinal adenocarcinoma (4.0% to 40.5%), urothelial neoplasms (10.5% to 36.7%), squamous cell carcinomas (up to 38%), and various types of sarcomas (up to 20%) and nonHodgkin lymphomas (up to 14%) . Homozygous MTAP deletion was found in 90% to 100% of cases with MTAP expression loss in most tumor categories. However, neuroendocrine tumors, Hodgkin lymphomas, and other lymphomas lacked MTAP deletions. MTAP deﬁciency was signiﬁcantly linked to unfavorable tumor phenotype in selected tumor entities and the presence of PD-L1 expression on tumor cells, absence of PDL1 expression on immune cells, and a low density of CD8+ lymphocytes. In summary, MTAP deﬁciency can occur in various tumor entities and is linked to unfavorable tumor phenotype and noninﬂamed tumor microenvironment, but isnot always related to deletions. MTAP IHC is of considerable diagnostic value for the detection of neoplastic transformation in multiple different applications. Key Words: MTAP, tissue micro array, immunohistochemistry, FISH, diagnostic marker (Am J Surg Pathol 2024;48:1245–1258) From the *Institute of Pathology, University Medical Center HamburgEppendorf, Martinistrasse, Hamburg, Germany; §Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse, Hamburg, Germany; †Institute of Pathology, Clinical Center Osnabrueck, Am Finkenhgel, Osnabrck, Germany; ‡Department of Pathology, Academic Hospital Fuerth, Jakob-Henle-Straße, Fürth, Germany; and ‖Institute of Pathology, University Hospital Basel, Schönbeinstrasse, Basel, Switzerland. The use of archived remnants of diagnostic tissues for manufacturing of TMAs and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, §12) and by the local ethics committee (Ethics commission Hamburg, WF-049/09) . All work has been carried out in compliance with the Helsinki Declaration. N.G., N.W., R. S., M.K., G. S., and L.B.: conception, design, data collection, data analysis, and manuscript writing. N.W., M.L., S.D.R., S.K., V.R., F.V., F.L., C.F., A.M.L., A.M., R. Schlichter, T.K., A.H., E.B., S. S., A.H.M., P.L., D.D., S.M., F.J., T. S.C., T.H., F.G. U., and C.B.: pathology data analysis, data interpretation, and collection of samples. N.G., R. Simon, M.K., and C.H.M.: data analysis. N.G., R. S., G. S., and M.K.: study supervision. All data generated or analyzed during this study are included in this published article. Conﬂicts of Interest and Sou

FAQs

How was MTAP deficiency measured and validated in this study?

MTAP expression loss was assessed using immunohistochemistry (IHC) on a tissue microarray. Complete MTAP loss was validated with fluorescence in situ hybridization (FISH).

In how many tumor categories and samples was MTAP loss observed?

The study analyzed 17,078 samples from 149 tumor entities, and MTAP loss was observed in 83 of 149 tumor categories.

What clinical or tumor microenvironment features are linked to MTAP deficiency?

MTAP deficiency was significantly associated with an unfavorable tumor phenotype, PD-L1 expression on tumor cells, absence of PD-L1 expression on immune cells, and a low density of CD8+ lymphocytes.

Sep 21, 2026

Uploaded by Miles

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