Molecular Pathology of Primary Non-small Cell Lung Cancer

Lung carcinoma is one of the most common human cancers and is estimated to have an incidence of approximately 2 million new cases per year worldwide with a 20% mortality rate. Lung cancer represents one of the leading causes of cancer related death in the world. Of all cancer types to affect the pulmonary system, non-small cell lung carcinoma comprises approximately 80-85% of all tumors. In the past few decades cytogenetic and advanced molecular techniques have helped define the genomic landscape of lung cancer, and in the process, revolutionized the clinical management and treatment of patients with advanced non-small cell lung cancer. The discovery of specific, recurrent genetic abnormalities has led to the development of targeted therapies that have extended the life expectancy of patients who develop carcinoma of the lungs. Patients are now routinely treated with targeted therapies based on identifiable molecular alterations or other predictive biomarkers which has led to a revolution in the field of pulmonary pathology and oncology. Numerous different testing modalities, with various strengths and limitations now exist which complicate diagnostic algorithms, however recently emerging consensus guidelines and recommendations have begun to standardize the way to approach diagnostic testing of lung carcinoma. Herein we provide an overview of the molecular genetic landscape of non-small cell lung carcinoma, with attention to those clinically relevant alterations which drive management, as well as review current recommendations for molecular testing.