Molecular alterations in non‐small‐cell lung cancer: Perspective for targeted therapy and specimen management for the bronchoscopist

Abstract

Major advances have occurred over the past decade in our understanding of lung cancer pathobiology. Increasing knowledge of molecular aberrations in lung cancer, specifically the discovery of two driver genes in pharmacologically targetable tyrosine kinases involved in growth factor receptor signalling, epidermal growth factor receptor and anaplastic lymphoma kinase, has been of major therapeutic and prognostic importance. This discovery has allowed for new, personalized approach to the management of lung cancer. Recognizing the importance of molecular signatures of lung cancer, the College of American Pathologists, International Association for the Study of Lung Cancer and Association for Molecular Pathology released the first guidelines for molecular testing in lung cancer.The introduction of minimally invasive needle techniques for the evaluation of lung cancer patients, such as endobronchial ultrasound transbronchial needle aspiration and oesophageal ultrasound-fine-needle aspiration, has revolutionized the way lung cancer patients are assessed. Samples obtained using the minimally invasive needle approaches have been shown to be sufficient not only for routine molecular testing but also for multigenic analysis. This allows bronchoscopist to assume an increasingly important role in the diagnostic workup of patients with lung cancer at all stages of the disease and contribute to personalizing the care of lung cancer patients.

Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks

“…Previously samples such as pleural fluids, bronchoscopic brushes, and CT fine-needle aspiration (FNA) samples were more common and were evaluated for molecular testing by single-gene approaches [2]. Mediastinal and hilar nodes can be easily sampled using EBUS-TBNA with few side effects and a 95% sensitivity for diagnosing malignancy [5, 7-9]. The EBUS-TBNA procedure can be accompanied by rapid on-site evaluation (ROSE) of sample material, using air-dried and Diff-Quik-stained cytology smears to provide immediate feedback for the proceduralist [10-12].…”

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging

“…and Yasufuku et al . both published excellent reviews with regard to multi‐modality systematic approaches to mediastinal lymph node staging and the role of the bronchoscopist in identifying molecular profiles in cases of non‐small cell lung cancer, respectively Accurate and efficient lymph node staging is essential for selecting the treatment modality, and determining the molecular profile of the tumour is necessary for choosing appropriate molecular target drugs and prolonging the patient's survival. Qvale et al .…”

“…The authors concluded that the detection of VEGF mRNA and SP-1 mRNA in bronchial brushing cells may be useful for identifying early-stage lung cancer. Ost et al and Yasufuku et al both published excellent reviews with regard to multi-modality systematic approaches to mediastinal lymph node staging and the role of the bronchoscopist in identifying molecular profiles in cases of non-small cell lung cancer, respectively 14,15 Accurate and efficient lymph node staging is essential for selecting the treatment modality, and determining the molecular profile of the tumour is necessary for choosing appropriate molecular target drugs and prolonging the patient's survival. Qvale et al 16 showed that paraneoplastic Hu and collapsing response mediator protein 5 antibodies, which were originally thought to be specific markers for paraneoplastic syndrome, are found only in smokers without cancer or neurological disease using sera obtained from 552 smokers (379 smokers with and 173 without COPD) and 300 healthy controls.…”

Comparison of 19‐gauge eXcelon and WANG MW‐319 transbronchial aspiration needles

“…To obtain cytology specimens, 20–22 gauge needles are usually used, whereas 19‐gauge needles are needed to obtain a core of tissue for histologic diagnosis . They can also provide sufficient specimens for molecular testing, which is essential in the era of personalized therapy …”