Molecular Pathogenesis of Non-Small Cell Lung Carcinomas

Abstract

Non-small cell lung carcinoma (NSCLC) from histological and biological perspectives is a complex neoplasm. The sequential preneoplastic changes have been defined for centrally arising squamous cell carcinomas (SCCs) of the lung, and they are less documented for peripherally arising adenocarcinomas. The main morphologic forms of preneoplastic lesions recognized in the lung are squamous dysplasias for SCC, and atypical adenomatous hyperplasia for adenocarcinoma. Several studies have provided information regarding the molecular characterization of lung preneoplastic changes, especially for SCC. These molecular changes have been detected in the histologically normal and abnormal respiratory epithelium of smokers and patients with lung cancer, phenomenon known as field of cancerization. Our improved understanding of the changes and origins of the field of cancerization can be applied clinically to improve early detection of lung cancer. In the last decade, significant progress has been made in the characterization of molecular abnormalities in NSCLC tumors that are being used as molecular targets and predictive biomarkers for patients’ selection for targeted therapy. As our understanding of the biology of the molecular pathogenesis of lung cancer evolves, there is an opportunity to use this knowledge for the development of novel chemoprevention strategies using those molecularly targeted agents used to treat advanced lung cancer, a concept coined as reverse migration. The rapid development of technologies for large-scale molecular analysis, includeing microarrays and next-generation sequencing will facilitate high-throughput molecular analysis of lung cancer preneoplastic lesions and the field of cancerization.