TY - JOUR
T1 - C-Met expression and MET amplification in malignant pleural mesothelioma
AU - Bois, Melanie C.
AU - Mansfield, Aaron S.
AU - Sukov, William R.
AU - Jenkins, Sarah M.
AU - Moser, Justin C.
AU - Sattler, Christopher A.
AU - Smith, Carin Y.
AU - Molina, Julian R.
AU - Peikert, Tobias
AU - Roden, Anja C.
N1 - Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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, 68.0 years; interquartile range, 61-75) had epithelioid (n = 97), biphasic (n = 18), or sarcomatoid (n = 34) MPM. Median follow-up was 10.1 months (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.
AB - 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, 68.0 years; interquartile range, 61-75) had epithelioid (n = 97), biphasic (n = 18), or sarcomatoid (n = 34) MPM. Median follow-up was 10.1 months (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.
KW - MET
KW - Mesothelioma
KW - Receptor tyrosine kinase
KW - Tyrosine kinase inhibitor
KW - c-Met
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U2 - 10.1016/j.anndiagpath.2016.04.007
DO - 10.1016/j.anndiagpath.2016.04.007
M3 - Article
C2 - 27402216
AN - SCOPUS:84964994665
SN - 1092-9134
VL - 23
SP - 1
EP - 7
JO - Annals of Diagnostic Pathology
JF - Annals of Diagnostic Pathology
ER -