title: c-Met expression and MET amplification in malignant pleural mesothelioma.
abstract: c-Met is a receptor tyrosine kinase shown to be overexpressed in malignant pleural mesothelioma (MPM). Whereas MET mutations have been identified in 3%-16% of MPMs, MET amplification has recently been reported in a single epithelioid MPM. We studied c-Met expression and MET amplification in a large MPM cohort and correlated results with morphologic and clinical features. We report the first case of MET amplification in sarcomatoid MPM. MPMs from surgical pathology files (1989-2014) were reviewed. c-Met immunohistochemistry was performed. Staining intensity and distribution were multiplied (H-score). Staining localization (cytoplasmic and/or membranous) was noted. Fluorescence in situ hybridization was performed using probes for MET and centromere 7. One hundred forty-nine patients (median age, 68.0years; interquartile range, 61-75) had epithelioid (n=97), biphasic (n=18), or sarcomatoid (n=34) MPM. Median follow-up was 10.1months (range, 0.1-222.5). One hundred thirty patients died of disease; 2 were alive with disease. c-Met was expressed in 147 MPMs. c-Met staining intensity, distribution, and H-score differed among the histologic subtypes (P=.015; P=.0001, and P=.0005, respectively), but none were predictive of survival. Epithelioid subtype had greater c-Met expression. MET amplification was identified in 1 sarcomatoid MPM and MET duplication in 1 epithelioid MPM; both had poor outcomes. Chromosome 7 aneusomy was observed in 54 of 144 (37.5%) MPMs and associated with decreased overall survival in sarcomatoid MPMs (hazard ratio=2.81; 95% confidence interval, 1.21-6.51; P=.01). In conclusion, c-Met is expressed in MPM, with significant differences in expression among histologic subtypes. MET amplification is a rare event in MPM, making it an unlikely common pathogenesis for c-Met expression.
authors.affiliation: Department of Laboratory Medicine and Pathology, Rochester, MN, USA.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Bois
authors.affiliation: Division of Medical Oncology, Rochester, MN, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Mansfield
authors.affiliation: Department of Laboratory Medicine and Pathology, Rochester, MN, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Sukov
authors.affiliation: Department of Health Sciences Research, Rochester, MN, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Jenkins
authors.affiliation: Department of Medicine, Rochester, MN, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Moser
authors.affiliation: Department of Laboratory Medicine and Pathology, Rochester, MN, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Sattler
authors.affiliation: Department of Health Sciences Research, Rochester, MN, USA.
authors.forename: Carin Y
authors.initials: CY
authors.lastname: Smith
authors.affiliation: Division of Medical Oncology, Rochester, MN, USA.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Molina
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Peikert
authors.affiliation: Department of Laboratory Medicine and Pathology, Rochester, MN, USA. Electronic address: Roden.anja@mayo.edu.
authors.forename: Anja C
authors.initials: AC
authors.lastname: Roden
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012509:Sarcoma / Q000175:diagnosis / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: MET; Mesothelioma; Receptor tyrosine kinase; Tyrosine kinase inhibitor; c-Met