MTAP loss does not stand in for CDKN2A deletion in peritoneal mesothelioma

Design

Retrospective diagnostic concordance study

Population

24 peritoneal mesotheliomas, 25 pleural mesotheliomas, 10 reactive proliferations

Primary outcome

Agreement of MTAP IHC and FISH with CDKN2A homozygous deletion

Effect

Peritoneal kappa 0.21 (IHC vs CDKN2A FISH); sensitivity 50%, specificity 75%

A study in Histopathology (published 21 September) compared MTAP immunohistochemistry, MTAP FISH and CDKN2A FISH in 24 peritoneal mesotheliomas, with 25 pleural mesotheliomas and 10 reactive mesothelial proliferations as controls.

In pleural mesothelioma, MTAP immunohistochemistry agreed perfectly with MTAP FISH and well with CDKN2A deletion, with 100% specificity and 68.8% sensitivity for the deletion. In peritoneal mesothelioma, MTAP immunohistochemistry still matched MTAP FISH (kappa 0.83) but agreed poorly with CDKN2A deletion (kappa 0.21, not significant), with 75% specificity and 50% sensitivity. All reactive proliferations were correctly classified by every assay.

MTAP immunohistochemistry is widely used as a cheap surrogate for CDKN2A homozygous deletion when separating mesothelioma from reactive proliferations. These data suggest the two genes are less often co-deleted in the peritoneum, so MTAP loss there should be read as a finding in its own right, and CDKN2A FISH is still needed where deletion status matters. The study is small and selected by molecular status.

• Do not use MTAP immunohistochemistry as a proxy for CDKN2A deletion in peritoneal mesothelioma.
• Request CDKN2A FISH where deletion status is needed in a peritoneal mesothelial lesion.
• Continue to use MTAP loss as supportive evidence of malignancy alongside BAP1 and morphology.
• Remember MTAP immunohistochemistry performs well as a CDKN2A surrogate in pleural mesothelioma.

Why it matters

A surrogate validated in the pleura is being applied in the peritoneum, where the genetics appear different.

Don't overread it

With 24 selected peritoneal cases, the accuracy estimates are imprecise.

The statistics, in plain English

Cohen's kappa measures agreement beyond chance: 1.0 is perfect, around 0.8 is strong, and 0.2 is poor. A kappa of 0.21 with a non-significant p-value means MTAP and CDKN2A results in peritoneal tumours agreed little better than chance.

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