title: Molecular testing in lung cancer in the era of precision medicine.
abstract: The clinical expectations how pathologists should submit lung cancer diagnosis have changed dramatically. Until mid 90-ties a clear separation between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) was mostly sufficient. With the invention of antiangiogenic treatment a differentiation between squamous and non-squamous NSCLC was requested. When epidermal growth factor receptor (EGFR) mutation was detected in patients with pulmonary adenocarcinomas and subsequent specific treatment with tyrosine kinase inhibitors (TKIs) was invented, sub-classification of NSCLC and molecular analysis of the tumor tissue for mutations was asked for. Pathologists no longer submit just a diagnosis, but instead are involved in a multidisciplinary team for lung cancer patient management. After EGFR several other driver genes such as echinoderm microtubule associated protein like 4-AL-Kinase 1 (EML4-ALK1), c-ros oncogene 1, receptor tyrosine kinase (ROS1), discoidin domain receptor tyrosine kinase 2 (DDR2), fibroblast growth factor receptor 1 (FGFR1) were discovered, and more to come. Due to new developments in bronchology (EUS, EBUS) the amount of tissue submitted for diagnosis and molecular analysis is decreasing, however, the genes to be analyzed are increasing. Many of these driver gene aberrations are inversions or translocations and thus require FISH analysis. Each of these analyses requires a certain amount of tumor cells or one to two tissue sections from an already limited amount of tissues or cells. In this respect new genetic test systems have been introduced such as next generation sequencing, which enables not only to detect multiple mutations in different genes, but also amplifications and fusion genes. As soon as these methods have been validated for routine molecular analysis this will enable the analysis of multiple genetic changes simultaneously. In this review we will focus on genetic aberrations in NSCLC, resistance to new target therapies, and also to methodological requirements for a meaningful evaluation of lung cancer tissue and cells.
authors: 1 Research Unit for Molecular Lung & Pleura Pathology, Institute of Pathology, Medical University of Graz, Austria ; 2 The Fingerland Department of Pathology, Charles University Faculty of Medicine and Faculty Hospital in Hradec Kralove, Czech Republic ; 3 Department of Pathology, Semmelweis University, Budapest, Molecular Oncology Research Group, HAS-SU, Budapest, Hungary ; 4 Department of Pathology, Cancer Center, 5 Roentgen Str. 02-781 Warsaw, Poland.
authors: Helmut H
authors: HH
authors: Popper
authors: 1 Research Unit for Molecular Lung & Pleura Pathology, Institute of Pathology, Medical University of Graz, Austria ; 2 The Fingerland Department of Pathology, Charles University Faculty of Medicine and Faculty Hospital in Hradec Kralove, Czech Republic ; 3 Department of Pathology, Semmelweis University, Budapest, Molecular Oncology Research Group, HAS-SU, Budapest, Hungary ; 4 Department of Pathology, Cancer Center, 5 Roentgen Str. 02-781 Warsaw, Poland.
authors: Ales
authors: A
authors: Ryska
authors: 1 Research Unit for Molecular Lung & Pleura Pathology, Institute of Pathology, Medical University of Graz, Austria ; 2 The Fingerland Department of Pathology, Charles University Faculty of Medicine and Faculty Hospital in Hradec Kralove, Czech Republic ; 3 Department of Pathology, Semmelweis University, Budapest, Molecular Oncology Research Group, HAS-SU, Budapest, Hungary ; 4 Department of Pathology, Cancer Center, 5 Roentgen Str. 02-781 Warsaw, Poland.
authors: József
authors: J
authors: Tímár
authors: 1 Research Unit for Molecular Lung & Pleura Pathology, Institute of Pathology, Medical University of Graz, Austria ; 2 The Fingerland Department of Pathology, Charles University Faculty of Medicine and Faculty Hospital in Hradec Kralove, Czech Republic ; 3 Department of Pathology, Semmelweis University, Budapest, Molecular Oncology Research Group, HAS-SU, Budapest, Hungary ; 4 Department of Pathology, Cancer Center, 5 Roentgen Str. 02-781 Warsaw, Poland.
authors: Wlodzimierz
authors: W
authors: Olszewski
keywords: Non-small cell lung carcinoma (NSCLC); molecular pathology; target (driver) genes; tissue based assessment