RT Journal Article
SR Electronic
T1 Clonality of multifocal nonsmall cell lung cancer: implications for staging and therapy
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1437
OP 1442
DO 10.1183/09031936.00105911
VO 39
IS 6
A1 Warth, Arne
A1 Macher-Goeppinger, Stephan
A1 Muley, Thomas
A1 Thomas, Michael
A1 Hoffmann, Hans
A1 Schnabel, Philipp A.
A1 Penzel, Roland
A1 Schirmacher, Peter
A1 Aulmann, Sebastian
YR 2012
UL http://erj.ersjournals.com/content/39/6/1437.abstract
AB Nonsmall cell lung cancers (NSCLCs) display a variety of morphological and molecular features. Accurate subtyping of NSCLC has been shown to predict patient survival as well as response rates and toxicities of specific drugs. Assessment of multifocal lung tumours and the distinction of synchronous primary tumours from intrapulmonary metastases represent an important problem as this decision significantly influences tumour staging and subsequent treatment strategies. In order to provide a basis for evidence-based treatment decisions in these patients, we analysed the clonal relationship of multifocal NSCLC with indistinguishable histomorphology in a series of 78 patients by allelotyping (using polymorphic short tandem repeat markers) as well as KRAS and epidermal growth factor receptor (EGFR) mutation testing. Our data demonstrate a common clonal origin indicative of intrapulmonary metastases in almost two-thirds (∼62%) of the cases, while ∼36% of multifocal NSCLC displayed unique molecular profiles suggesting separate primary tumours. Divergent KRAS and/or EGFR mutations were observed in ∼8% of all cases. With the increased availability of EGFR-targeted therapy options, nonresectable, multifocal NSCLC with diverging KRAS and/or EGFR mutations are likely to show different treatment responses, underlining the need to separately analyse multifocal tumours. Obviously, this also holds true for further, novel molecular predictors of targeted therapies.