p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma

An atypical mesothelial proliferation along the pleural or peritoneal surface without evidence of invasive tumor poses a diagnostic challenge. Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in mesothelial proliferations, but correlations of p16 status between atypical surface proliferations and underlying mesothelioma have not been described. We used p16 FISH to investigate 11 pleural and 7 peritoneal mesotheliomas that had both an invasive component and a separate surface mesothelial proliferation. In 5/11 pleural samples and 1/7 peritoneal samples, the invasive mesotheliomas showed homozygous deletion of p16 (all cases in excess of 90% of cells deleted); the surface proliferation in all 6 cases with deletion in the invasive tumor was also p16 deleted. Conversely, the 12 tumors that did not show p16 deletion in the invasive compartment also did not have deletion in the surface component. We conclude that (1) surface mesothelial proliferations near invasive mesotheliomas show the same pattern of p16 by FISH as the underlying tumor and may represent in situ disease or growth of the underlying mesothelioma along the serosal surface; (2) p16 deletion in mesothelial surface proliferations is strongly associated with p16 deletion in underlying mesotheliomas, and biopsies consisting of pure surface mesothelial proliferations that are p16 deleted allow a diagnosis of mesothelioma without an additional biopsy if there is clinical (thoracosopic/laparoscopic) or radiologic evidence of diffuse pleural or peritoneal tumor; (3) however, the absence of p16 deletion in surface proliferations does not rule out underlying invasive mesothelioma.