MTAP loss in lung cancer: immunohistochemistry matched sequencing in 97%

Design

Retrospective single-institution cohort with IHC–NGS comparison subset

Population

5,233 non-small cell lung cancers; 105 with paired testing

Primary outcome

MTAP deletion prevalence and IHC–NGS concordance

Effect

Deletion 5.6%; concordance 97.3%

This study reviewed 5,233 non-small cell lung cancers with panel sequencing that fully covered the MTAP gene, and compared sequencing with MTAP immunohistochemistry in 105 cases.

Homozygous MTAP deletion was found in 5.6% of tumours, more often in adenocarcinomas from never or light smokers and alongside EGFR mutations or ALK fusions. After quality control, and excluding sequencing from tumours with 30% or less tumour content, the two methods agreed in 97.3%. About 13% of MTAP-deficient tumours showed heterogeneous staining, and immunohistochemistry was more sensitive when tumour content was low or loss was subclonal.

MTAP loss creates a vulnerability that drugs in development aim to exploit. Laboratories should expect requests and know that immunohistochemistry is a reliable, cheaper route that also works on small or poor samples.

• Consider MTAP immunohistochemistry when sequencing tumour content is 30% or less
• Report heterogeneous MTAP staining rather than calling it retained or lost
• Interpret copy-number calls cautiously in non-diploid tumours
• Expect MTAP deletion to co-occur with EGFR and ALK alterations

Why it matters

MTAP status may soon guide therapy, and immunohistochemistry offers a practical route where sequencing is limited.

The statistics, in plain English

97.3% concordance in 105 cases means about 3 disagreements, each with an explanation. The comparison was in a selected subset, not all 5,233 tumours.

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