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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Brune, MM; Roma, L; Chijioke, O; Alborelli, I; Zacharias, M; Bubendorf, L; Vlajnic, T; Deigendesch, N; Pollinger, J; Hirschmann, P; König, D; Ott, S; Savic-Prince, S; Bubendorf, L.
MTAP expression by immunohistochemistry: a novel biomarker in non-small cell cancer of the lung.
J Thorac Oncol. 2025; Doi: 10.1016/j.jtho.2025.08.014
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Autor*innen der Med Uni Graz:
Zacharias Martin
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Abstract:
INTRODUCTION: Loss of MTAP serves as a potential predictive marker of response to cooperative PRMT5 inhibitors and as negative predictor of response to immune-checkpoint inhibitors. We investigated the prevalence of MTAP deficiency by immunohistochemistry (IHC) in NSCLC as a surrogate for MTAP loss. METHODS: MTAP IHC was performed on 698 NSCLC samples. Data from routine next-generation sequencing, analyzed with the OncomineTM Precision Assay (OPA-NGS, Thermo Fisher), were available in 426 cases, including CDKN2A copy number variation (CNV) data in 411 cases. Our findings were compared to data from The Cancer Genome Atlas (TCGA). RESULTS: MTAP deficiency by IHC was found in 18.2% of NSCLC. CDKN2A loss by OPA-NGS - used as a surrogate for MTAP loss - was significantly associated with MTAP deficiency by IHC, but was found in only 28.4% of the MTAP deficient NSCLC analyzed for CDKN2A CNV. In the TCGA cohort, only 72.9% of NSCLC with CDKN2A loss had a concurrent MTAP loss defined by CNV. CONCLUSION: MTAP IHC seems to be better suited than OPA-NGS to assess the MTAP status in NSCLC, especially as the MTAP gene is not specifically covered within this panel. CDKN2A loss is not a reliable MTAP loss surrogate, as it overestimated MTAP loss in more than 25% of the cases in the TCGA cohort.

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