- Design
- Retrospective institutional cohort with IHC–NGS comparison subset
- Population
- 5,233 non-small cell lung cancers with NGS; 105 with paired IHC
- Primary outcome
- Concordance of MTAP loss by IHC and NGS
- Effect
- Homozygous deletion 5.6%; IHC–NGS concordance 97.3%
MTAP deletion at 9p21 is emerging as a target for synthetic-lethal therapies. A large US institution reviewed NGS on 5,233 non-small cell lung cancers and compared NGS with MTAP immunohistochemistry in 105.
Homozygous MTAP deletion was found in 5.6% and was enriched in adenocarcinomas from never or light smokers and in EGFR-mutant or ALK-rearranged tumours. After quality control and excluding NGS from tumours with 30% or less tumour content, IHC and NGS agreed in 97.3%. About 13% of loss cases showed heterogeneous staining, and IHC caught loss that sequencing missed in low-cellularity or subclonal samples.
IHC is cheaper and more widely available in India than broad NGS panels, so it is a practical first test where MTAP status may matter for trials.
- Consider MTAP immunohistochemistry where NGS is unavailable or tumour content is low.
- Interpret NGS copy-number calls cautiously when tumour content is 30% or less.
- Report heterogeneous MTAP staining rather than calling it simply retained or lost.
- Use internal controls in non-neoplastic cells to confirm a true loss.
Why it matters
It gives laboratories without broad sequencing a validated route to a new biomarker.
The statistics, in plain English
Concordance of 97.3% was measured in 105 cases after careful quality control; agreement in routine practice may be lower.
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