1. c-MET immunohistochemistry for differentiating malignant mesothelioma from benign mesothelial proliferations
- Author
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He Zhen Ren, Simon Cheung, and Andrew Churg
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,C-Met ,Receptor, ErbB-3 ,Cell ,Epithelium ,Pathology and Forensic Medicine ,Surgical pathology ,Diagnosis, Differential ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Predictive Value of Tests ,medicine ,Biomarkers, Tumor ,Humans ,Mesothelioma ,Cell Proliferation ,BAP1 ,Tissue microarray ,business.industry ,Tumor Suppressor Proteins ,Mesothelioma, Malignant ,Proto-Oncogene Proteins c-met ,medicine.disease ,Immunohistochemistry ,Staining ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,business ,Microtubule-Associated Proteins ,Ubiquitin Thiolesterase - Abstract
Summary 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-RMPs), 23 reactive spindle cell mesothelial proliferations, 45 epithelioid malignant mesotheliomas (EMMs), and 26 sarcomatoid/desmoplastic mesotheliomas (SMMs) for c-MET and compared the results with 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 of 33 (all trace) E-RMPs compared with 36 of 45 (80%) EMMs (chi-square comparing reactive and malignant = 39.80, p = 1.2 × 10−8). The H-score was >3 (moderate or strong) in 24 of 45 (53%) EMMs. Addition of BAP1 staining to the c-MET–negative/trace EMM increased sensitivity to 75% (32/42), whereas similar addition of MTAP staining increased sensitivity to 77% (33/43). No benign spindle cell proliferations showed staining compared with 10 of 26 (38%) positive SMMs, but only 4 (15%) SMMs were classified as moderate or strong. We conclude that moderate/strong c-MET staining can be used to support a diagnosis of EMM vs an epithelial reactive proliferation. c-MET is too insensitive to use for detecting SMM.
- Published
- 2020