Prevalence of S-methyl-5′-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer
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 non-Hodgkin 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 PD-L1 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 is not always related to deletions. MTAP IHC is of considerable diagnostic value for the detection of neoplastic transformation in multiple different applications.
Authors
- Thilo Hackert (ORCID: https://orcid.org/0000-0002-7012-1196)
- Lukas Bubendorf (ORCID: https://orcid.org/0000-0001-5970-1803)
- Maximilian Lennartz (ORCID: https://orcid.org/0000-0002-1572-8200)
- Guido Sauter (ORCID: https://orcid.org/0000-0002-9024-4978)
- Anne Menz (ORCID: https://orcid.org/0000-0002-4364-6464)
- Florian Lutz (ORCID: https://orcid.org/0000-0002-3778-3286)
- Eike Burandt (ORCID: https://orcid.org/0000-0002-5705-9084)
- Stefan Steurer (ORCID: https://orcid.org/0000-0002-7199-3615)
- Natalia Gorbokon (ORCID: https://orcid.org/0009-0001-6680-8788)
- Christoph Fraune (ORCID: https://orcid.org/0000-0002-0833-9549)
- Till Krech
- Andreas M. Luebke (ORCID: https://orcid.org/0000-0003-1464-6964)
- Sarah Jane Pauline Minner (ORCID: https://orcid.org/0000-0003-0765-3568)
- Sebastian Dwertmann Rico
- Viktor Reiswich
- Claudia Hube‐Magg (ORCID: https://orcid.org/0000-0001-7542-4340)
- Simon Kind
- Patrick Lebok (ORCID: https://orcid.org/0000-0003-3652-532X)
- Frank Jacobsen (ORCID: https://orcid.org/0009-0009-8047-580X)
- Florian Viehweger
- Faik G. Uzunoǧlu (ORCID: https://orcid.org/0000-0002-6890-4829)
- Till Sebastian Clauditz (ORCID: https://orcid.org/0000-0002-4257-856X)
- Christian Bernreuther (ORCID: https://orcid.org/0000-0003-3939-322X)
- Ronald Simon (ORCID: https://orcid.org/0000-0003-0158-4258)
- Andrea Hinsch (ORCID: https://orcid.org/0000-0001-5868-1185)
- Martina Kluth (ORCID: https://orcid.org/0000-0003-4782-4616)
- David Dum (ORCID: https://orcid.org/0000-0002-7884-4313)
- Andreas Holger Marx (ORCID: https://orcid.org/0000-0002-5182-8364)
- Ria Schlichter
- Niklas Wößner
Institutions
- Universität Hamburg (DE)
- University Hospital of Basel (CH)
- University Medical Center Hamburg-Eppendorf (DE)
- Klinikum Fürth (DE)
Publication Details
- Journal
- The American Journal of Surgical Pathology
- Published
- 2024-08-12
- DOI
- https://doi.org/10.1097/pas.0000000000002297
- Citations
- 16
- Primary Topic
- Cancer-related gene regulation
- Type
- article
- Field-Weighted Citation Impact
- 3.74