BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Malignant Peritoneal Mesothelioma

Objective: Peritoneal malignant mesothelioma (PMM) is an uncommon tumor, only 7-9% of all mesothelioma in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging.

Methods: To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine BAP1, and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs, and 10 RMHs.

Results: Seventeen of the mesotheliomas were classified as diffuse, while 5 were localized. Loss of BAP1 was seen in 10/21 (45%) of PMM, but all PPSC and all RMH were BAP1-positive. For the differentiation of PMM from PPSC and RMH of the peritoneum, the sensitivity and specificity for BAP1 in mesothelioma were 43% and 100%, respectively. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 (85%) of PMM, but in none of RMH.

Conclusion: BAP1 loss is not a sensitive test, although specificity is very high for differentiating PMM from both PPSC and RMH. Homozygous deletion of 9p21 may be helpful for differentiating PMM from RMH.