Peritoneal mesothelioma: read MTAP loss on its own terms

Design

Diagnostic concordance study with FISH and immunohistochemistry

Population

24 peritoneal and 25 pleural mesotheliomas; 10 reactive mesothelial proliferations

Primary outcome

Agreement of MTAP IHC and FISH with CDKN2A homozygous deletion

Effect

Pleural: MTAP IHC specificity 100%; peritoneal: kappa vs CDKN2A FISH 0.21, specificity 75%, sensitivity 50%

In pleural mesothelioma, loss of MTAP on immunohistochemistry is widely used as a surrogate for homozygous CDKN2A deletion, which helps separate mesothelioma from reactive mesothelial proliferation. This Histopathology study, published on 21 September 2026, tested whether that holds in the peritoneum. It compared MTAP immunohistochemistry, MTAP FISH and CDKN2A FISH in 24 peritoneal mesotheliomas, 25 pleural mesotheliomas and 10 reactive proliferations.

In pleural cases, MTAP immunohistochemistry agreed perfectly with MTAP FISH and was 100% specific (68.8% sensitive) for CDKN2A deletion. In peritoneal cases, MTAP immunohistochemistry still agreed well with MTAP FISH (kappa 0.83), but agreement with CDKN2A FISH was poor (kappa 0.21), with 75% specificity and 50% sensitivity. All reactive proliferations retained both markers.

The peritoneal cohort was small and was selected by marker status, so the figures are not prevalence estimates. The practical message is still clear: in the peritoneum, MTAP and CDKN2A are separate events, so MTAP loss supports malignancy in its own right but should not be reported as evidence of CDKN2A deletion.

• Do not report MTAP loss as a surrogate for CDKN2A deletion in peritoneal mesothelioma
• Use CDKN2A FISH when CDKN2A status itself is needed in peritoneal cases
• Consider MTAP loss as an adjunct marker favouring malignancy over a reactive process
• Keep using MTAP as a CDKN2A surrogate in pleural mesothelioma, where agreement was high
• Combine with BAP1 and morphology rather than relying on a single marker

Why it matters

A surrogate validated in the pleura does not transfer automatically to the peritoneum.

Don't overread it

A small, selected cohort; the sensitivity and specificity figures may not apply to unselected cases.

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 between MTAP and CDKN2A in peritoneal cases means the two often disagreed.

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