WCLC 2025 - Posters & ePosters-PT1.06.03 Loss of MTAP Expression in Thymic Carcinomas: Insights From a Retrospective Multi-Institutional, Global Study

PT1.06.03 Loss of MTAP Expression in Thymic Carcinomas: Insights From a Retrospective Multi-Institutional, Global Study

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This multi-institutional global study analyzed 64 thymic carcinoma cases to assess the prevalence of loss of MTAP (Methylthioadenosine Phosphorylase) expression and associated molecular alterations. MTAP loss is clinically relevant because tumors deficient in MTAP may be susceptible to targeted therapies such as second-generation PRMT5 inhibitors and antifolates affecting de novo purine synthesis. The study involved retrospective data from institutional databases and used immunohistochemistry (IHC) for MTAP detection, complemented by molecular testing including Foundation One, CARIS, or laboratory-developed NGS assays.<br /><br />Key findings showed that loss of MTAP expression occurred in 20.3% of thymic carcinomas (12.5% complete loss and 7.8% subclonal loss). The highest frequency of MTAP loss was found in squamous cell carcinomas (45.3%), with some adenosquamous and sarcomatoid subtypes also affected. Molecular alterations in these tumors included mutations/deletions in CDKN2A/B, TP53, FGFR3, EGFR, ERBB2 amplification, BAP1, and SETD2. Importantly, loss of MTAP expression was sometimes observed without identifiable MTAP gene mutations, indicating alternative mechanisms of inactivation.<br /><br />Clinically, the cohort had a median patient age of ~60 years, with 58.5% males. The data support that about one-fifth of thymic carcinoma patients may potentially benefit from MTAP-targeted therapies, warranting further investigation. Future studies are planned to evaluate correlations of MTAP expression loss with clinical outcomes. The study builds on previous reports linking MTAP loss and homozygous CDKN2A deletion in thymic carcinoma, primarily in the squamous subtype, while lymphoepithelial subtypes generally retained MTAP.<br /><br />In conclusion, this study identifies a significant subset of thymic carcinomas characterized by MTAP loss and specific molecular profiles, highlighting opportunities for precision oncology interventions. The findings encourage further exploration of loss of MTAP as a prognostic and predictive biomarker in thymic cancer management.

Asset Subtitle

Anja Roden

Meta Tag

Speaker Anja Roden

Topic Pathology and Biomarkers

Keywords

thymic carcinoma

MTAP loss

molecular alterations

PRMT5 inhibitors

immunohistochemistry

CDKN2A/B mutations

squamous cell carcinoma

precision oncology

targeted therapies

biomarkers