EGFR, KRAS, BRAF and ALK gene alterations in lung adenocarcinomas: patient outcome, interplay with morphology and immunophenotype
Open Access
- 29 August 2013
- journal article
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 43 (3), 872-883
- https://doi.org/10.1183/09031936.00018013
Abstract
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 adenocarcinomashttp://ow.ly/skRkyThis publication has 43 references indexed in Scilit:
- ERCC1 Isoform Expression and DNA Repair in Non–Small-Cell Lung CancerThe New England Journal of Medicine, 2013
- Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1Proceedings of the National Academy of Sciences of the United States of America, 2012
- Thymidylate Synthase Protein Expression by IHC and Gene Copy Number by SISH Correlate and Show Great Variability in Non–Small Cell Lung CancerJournal of Thoracic Oncology, 2012
- Frequency of Driver Mutations in Lung Adenocarcinoma from Female Never-Smokers Varies with Histologic Subtypes and Age at DiagnosisClinical Cancer Research, 2012
- ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: a meta-analysisMolecular Biology Reports, 2012
- Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF MutationsJournal of Clinical Oncology, 2011
- Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancerBritish Journal of Cancer, 2011
- Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung CancerThe New England Journal of Medicine, 2010
- A Novel, Highly Sensitive Antibody Allows for the Routine Detection ofALK-Rearranged Lung Adenocarcinomas by Standard ImmunohistochemistryClinical Cancer Research, 2010
- Gefitinib or Carboplatin–Paclitaxel in Pulmonary AdenocarcinomaThe New England Journal of Medicine, 2009