Molecular pathology in lung cancer

Increasing understanding of genomic changes in cancer is transforming the diagnosis and treatment of a subset of lung cancers. A significant proportion of lung adenocarcinomas harbour biologically relevant or targetable somatic genetic changes such as mutations, amplifications or translocations in a range of genes, including KRAS, EGFR, ALK, ROS1, MET and BRAF. This review highlights the key actionable somatic changes seen in lung cancer, with particular emphasis on epidermal growth factor receptor mutations and ALK gene rearrangements in adenocarcinoma, as well as identifying promising new targets in squamous cell carcinoma of the lung. Accurate and sensitive molecular testing is essential to ensure patients with this poor prognosis disease receive the correct therapy, but mutation testing in lung cancer poses particular challenges. As the majority of patients with lung cancer present with advanced disease that is unsuitable for resection, many biopsies submitted for molecular testing are small biopsies such as core biopsies and fine needle aspirate biopsies, often with only a very small amount of diagnostic material available for mutation analysis. This paper highlights the need for good communication between clinicians, radiologists and pathologists to ensure optimal samples for molecular testing and the benefits of testing for multiple genes in one assay.