Pulmonary adenocarcinoma: a renewed entity in 2011

Abstract

Lung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non-smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention.

Figure 1

Molecular analysis of the lung field cancerization. It is unknown whether changes in expression in the lung field cancerization are associated with the development of a particular subtype of non-small cell lung cancer (NSCLC), that is, adenocarcinomas compared with squamous-cell carcinomas (SCC). Analysing local and distant field cancerization independently for lung adenocarcinomas and SCC may shed light on events common or unique to the molecular pathogenesis of the two major subtypes of NSCLC. Such a ‘compartmental’ approach in studying the field cancerization may unravel biomarkers that can guide personalized prevention strategies suitable for each different NSCLC subtype.