Loss of p16 Expression Differentiates Malignant Mesothelioma from Benign Mesothelial Proliferation.
Hakan Aydin, Debra Chute, Bin Yang. Cleveland Clinic, OH
Background: Although several antibodies relatively specific to mesothelial cells have been developed in discriminating mesothelial cells from adenocarcinoma, a few ancillary tools are available clinically to differentiate benign from malignant mesothelial proliferation. Recent molecular studies indicate that alteration of the p16 gene either by deletion or promoter hypermethylation is attributed to malignant transformation of mesothelial cells. However, difference on expression of p16 protein between benign and malignant mesothelial cells has not well investigated. We investigated the utility of p16 immunohistochemical staining in differentiating benign mesothelial proliferation from malignant mesothelioma.
Design: A total of 41 cases of mesothelial proliferation were retrospectively identified from our hospital archiving system, which include 10 cases of benign peritoneal multilocular mesothelial inclusion cysts (MMIC) and 31 cases of malignant mesothelioma. The latter encompasses 16 cases of surgically resected mesothelioma and 15 cases of cell blocks from pleural or peritoneal effusions. Expression of p16 was evaluated with p16 antibody kit (MTM, Germany) using the BenchmarkXT® instrument (Ventana Medical Systems, Inc., Tucson, AZ). Immunohistochemical staining pattern for p16 was evaluated with intensity (0, 1+, 2+ and 3+) and percentage of mesothelial cells.
Results: Among 10 cases of benign mesothelial proliferation (MMIC), strong (3+) and diffuse (>95% of cells) p16 immunoreactivity was seen in all the cases. In contrast, loss of p16 expression was seen in all 31 cases of malignant mesothelioma, including 80.7% (25/31) cases with total p16 negativity and 19.3% (6/31) cases with partial and weak p16 immunoreactivity (20-50% of cells). There is significant difference (p<0.001) of p16 immunoreactivity between benign mesothelial proliferation and malignant mesothelioma.
Conclusions: Overexpression of p16 protein is seen in benign multilocular mesothelial inclusion cysts. In contrast, loss of p16 protein is a hallmark of malignant mesothelioma cells. Immunohistochemical staining for p16 can be a useful ancillary tool in differentiating benign and malignant mesothelial proliferation.
Category: Bone & Soft Tissue
Monday, February 28, 2011 1:00 PM
Poster Session II # 11, Monday Afternoon