RT Journal Article
SR Electronic
T1 <em>EGFR</em>, <em>KRAS</em>, <em>BRAF</em> and <em>ALK</em> gene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 872
OP 883
DO 10.1183/09031936.00018013
VO 43
IS 3
A1 Arne Warth
A1 Roland Penzel
A1 Heike Lindenmaier
A1 Regine Brandt
A1 Albrecht Stenzinger
A1 Esther Herpel
A1 Benjamin Goeppert
A1 Michael Thomas
A1 Felix J.F. Herth
A1 Hendrik Dienemann
A1 Philipp A. Schnabel
A1 Peter Schirmacher
A1 Hans Hoffmann
A1 Thomas Muley
A1 Wilko Weichert
YR 2014
UL http://erj.ersjournals.com/content/43/3/872.abstract
AB Numerous studies have been published on single aspects of pulmonary adenocarcinoma (ADC). To comprehensively link clinically relevant ADC characteristics, we evaluated established morphological, diagnostic and predictive biomarkers in 425 resected ADCs. Morphology was reclassified. Cytokeratin-7, thyroid transcription factor (TTF)1, napsin A, thymidylate synthase and excision repair cross-complementing rodent repair deficiency complementation group-1 expression, anaplastic lymphoma kinase rearrangements as well as epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS) and v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) mutations were analysed. All characteristics were correlated with clinical and survival parameters. Morphological ADC subtypes were significantly associated with smoking history and distinct patterns of diagnostic biomarkers. KRAS mutations were prevalent in male smokers, while EGFR mutations were associated with female sex, nonsmoking and lepidic as well as micropapillary growth patterns. TTF1 expression (hazard ratio (HR) for overall survival 0.61, p=0.021) and BRAF mutations (HR for disease-free survival 2.0, p=0.046) were found to be morphology- and stage-independent predictors of survival in multivariate analysis. Adjuvant radio-/chemotherapy, in some instances, strongly impacted on the prognostic effect of both diagnostic and predictive biomarkers. Our data draw a comprehensive picture of the prevalence and interplay of established histological and molecular ADC characteristics. These data will help to develop time- and cost-effective diagnostic and treatment algorithms for ADC. Morphological, diagnostic and predictive biomarkers, and clinical characteristics of pulmonary adenocarcinomas http://ow.ly/skRky