PT  - JOURNAL ARTICLE
AU  - Arne Warth
AU  - Roland Penzel
AU  - Heike Lindenmaier
AU  - Regine Brandt
AU  - Albrecht Stenzinger
AU  - Esther Herpel
AU  - Benjamin Goeppert
AU  - Michael Thomas
AU  - Felix J.F. Herth
AU  - Hendrik Dienemann
AU  - Philipp A. Schnabel
AU  - Peter Schirmacher
AU  - Hans Hoffmann
AU  - Thomas Muley
AU  - Wilko Weichert
TI  - <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
AID  - 10.1183/09031936.00018013
DP  - 2014 Mar 01
TA  - European Respiratory Journal
PG  - 872--883
VI  - 43
IP  - 3
4099  - http://erj.ersjournals.com/content/43/3/872.short
4100  - http://erj.ersjournals.com/content/43/3/872.full
SO  - Eur Respir J2014 Mar 01; 43
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