The Diagnostic Utility of p16/CDKN2A FISH in Distinction between Sarcomatoid Mesothelioma and Fibrous Pleuritis
Kenzo Hiroshima, Di Wu, Shinji Matsumoto, Kazuki Nabeshima, Toshikazu Yusa, Daisuke Ozaki, Michio Fujino, Yukio Nakatani. Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan; Fukuoka University, Fukuoka, Japan; Chiba Rosai Hospital, Ichihara, Chiba, Japan; Chiba East Hospital, Chiba, Japan; Chiba University, Chiba, Japan
Background: In sarcomatoid mesotheliomas, the distinction from fibrous pleuritis is sometimes difficult, especially when the amount of tumor in the biopsy is small, cells are bland-appearing, immunohistochemistry is inconclusive, or tumor invasion of the stroma cannot be assessed. However, the correct diagnosis is crucial to patient care and compensation. It is reported that most mesotheliomas have deletion of p16/CDKN2A and methylated p16/CDKN2A promoters. Homozygous p16/CDKN2A deletion detected by FISH is reported to be a powerful technique for confirming the diagnosis of mesothelioma over reactive mesothelial cells. We studied the diagnostic utility of p16/CDKN2A FISH and detection of the methylation status of p16/CDKN2A for the diagnosis of sarcomatoid mesothelioma.
Design: A retrospective analysis of 69 surgical biopsies from 67 patients with histologically confirmed malignant pleural mesothelioma (epithelioid 33, biphasic 12, sarcomatoid 22) was performed. Methylation specific PCR were attempted in 62 cases. FISH for deletions of p16/CDKN2A was performed in 22 cases of mesothelioma and in 3 cases of fibrous pleuritis. The diagnosis of mesothelioma was rendered based on histology, results of immunohistochemistry, image studies, and clinical course.
Results: Homozygous deletion of p16/CDKN2A was observed in 11% (1/9) of epithelioid mesotheliomas and in 56% (5/9) of sarcomatoid mesotheliomas. Heterozygous deletion was observed in 67% (6/9) of epithelioid mesotheliomas, 100% (3/3) of biphasic mesotheliomas, and 44% (4/9) of sarcomatoid mesotheliomas. Of fibrous pleuritis cases, none had a deletion of p16/CDKN2A. Methylation of p16/CDKN2A was observed in 13 of 59 informative cases (22%). It was observed in 17% (5/30) of epithelioid mesotheliomas, in 27% (3/11) of biphasic mesotheliomas, and in 22% (4/18) of sarcomatoid mesotheliomas. None of the tumors with homozygous deletion of p16/CDKN2A was methylated. Unmethylated epithelioid mesothelioma had changed to methylated pleomorphic mesothelioma during the course of chemotherapy for three years in one patient.
Conclusions: Our results demonstrated that homozygous deletion of p16/CDKN2A is more common in sarcomatoid mesotheliomas than in epithelioid mesotheliomas, and p16/CDKN2A FISH analysis can be a reliable test for the distinction between sarcomatoid mesothelioma and fibrous pleuritis.
Tuesday, March 20, 2012 2:30 PM
Platform Session: Section D, Tuesday Afternoon