LAUSR

The separation of benign from malignant mesothelial proliferations can be a difficult problem for the surgical pathologist. c-MET is a receptor tyrosine kinase that is overexpressed and detectable by immunohistochemistry in many malignancies, including malignant mesothelioma. Whether c-MET is also expressed in benign mesothelial reactions is unclear from the literature. To determine whether c-MET immunohistochemistry can separate benign from malignant mesothelial processes, we stained 2 tissue microarrays containing 33 reactive epithelioid mesothelial proliferations (E-RMP), 23 reactive spindle cell mesothelial proliferations (S-RMP), 45 epithelioid malignant mesotheliomas (EMM), and 26 sarcomatoid/desmoplastic mesotheliomas (SMM) for c-MET, and compared the results to immunohistochemistry for two established markers, BAP1 and methylthioadenosine phosphorylase (MTAP). Membrane staining for c-MET was evaluated using a 12 point H-score classified as negative (score 0), trace (score 1-3), moderate (score 4-6), and strong (score 8-12). Staining was seen in only 3/33 (all trace) E-RMP compared to 36/45 (80%) EMM. (Chi-square comparing reactive and malignant =39.80, p=1.2 x 10-8). The H-score was >3 (moderate or strong) in 24/45 (53%) EMM. Addition of BAP1 staining to the c-MET negative/trace EMM increased sensitivity to 32/42 (76%), while similar addition of MTAP staining increased sensitivity to 33/43 (77%). No benign spindle cell proliferations showed staining compared to 10/26 (38%) positive SMM mesotheliomas, but only 4 (15%) SMM were classified as moderate or strong. We conclude that moderate/strong c-MET staining can be used to support a diagnosis of epithelioid malignant mesothelioma vs an epithelial reactive proliferation. c-MET is too insensitive to use for detecting SMM.