Characterizing the distribution of alterations in mesothelioma and their correlation to morphology

Mesothelioma is a lethal disease that arises from the serosal lining of organ cavities. Several recurrent alterations have been observed in pleural and peritoneal -mesotheliomas, including in BAP1, NF2, and CDKN2A. Although specific histopathologic parameters have been correlated with prognosis, it is not as well known whether genetic alterations correlate with histologic findings.

We reviewed 131 mesotheliomas that had undergone next-generation sequencing (NGS) at our institutions after pathologic diagnosis. There were 109 epithelioid mesotheliomas, 18 biphasic mesotheliomas, and 4 sarcomatoid mesotheliomas. All our biphasic and sarcomatoid cases arose in the pleura. Of the epithelioid mesotheliomas, 73 were from the pleura and 36 were from the peritoneum. On average, patients were 66 years of age (range, 26-90 years) and predominantly male (92 men, 39 women).

The most common alterations identified were in BAP1, CDKN2A, NF2, and TP53. Twelve mesotheliomas did not show a pathogenic alteration on NGS. For epithelioid mesotheliomas in the pleura, the presence of an alteration in BAP1 correlated with low nuclear grade (P = .04), but no correlation was found in the peritoneum (P = .62). Similarly, there was no correlation between the amount of solid architecture in epithelioid mesotheliomas and any alterations in the pleura (P = .55) or peritoneum (P = .13). For biphasic mesotheliomas, cases with either no alteration detected or with an alteration in BAP1 were more likely to be epithelioid predominant (>50% of the tumor, P = .0001), and biphasic mesotheliomas with other alterations detected and no alteration in BAP1 were more likely to be sarcomatoid predominant (>50% of the tumor, P = .0001).

This study demonstrates a significant association between morphologic features associated with a better prognosis and an alteration in BAP1.