Molecular Diagnostics of Lung Carcinomas

Context.-The development of targeted therapies in the treatment of lung carcinoma is a rapidly growing area that requires a precise histologic classification of lung carcinomas and the implementation into clinical practice of testing for predictive biomarkers of therapy response. Molecular testing has added another layer of complexity in the routine workup of rather limited diagnostic tumor tissue. Objective.-To review the most important lung carcinoma biomarkers predictive of response and to discuss proposed routine molecular testing in clinical practice. Data Sources.-PubMed (US National Library of Medicine)-available review articles, peer-reviewed original articles, and experience of the author. Conclusions.-Histologic profile, clinical characteristics, and mutational profile of lung carcinoma have all been reported as predictive factors of response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and other targeted therapies. Recently published results of large clinical trials indicate that mutational profiling, particularly identification of activating epidermal growth factor receptor (EGFR) mutations, is the best predictor for EGFR-TKI response. Despite all these observations, molecular profiling of lung carcinomas has not been standardized or validated in clinical practice. Rapid development of targeted therapies will probably require molecular testing for a panel of mutations to identify molecular subtypes of non-small cell lung carcinomas that will benefit from new therapeutic approaches in personalized patient care. (Arch Pathol Lab Med. 2011;135:622-629)