Field cancerization in non-small cell lung cancer: implications in disease pathogenesis

Abstract

Lung cancer, of which non-small cell lung cancer (NSCLC) composes the majority, is the leading cause of cancer-related deaths in the United States and worldwide. NSCLCs are tumors 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, in particular of adenocarcinomas, is still largely unknown. Earlier studies have highlighted a field cancerization phenomenon in which histologically normal-appearing tissue adjacent to neoplastic and pre-neoplastic lesions display molecular abnormalities, some of which are in common with those in the tumors. This review will summarize advances in understanding the field cancerization phenomenon and the potential relevance of this knowledge to gain important and novel insights into the molecular pathogenesis of NSCLC as well as to subsequent development of biomarkers for early detection of lung cancers and possibly personalized prevention.

Figure 1.

Molecular mapping analysis of the field cancerization in non–small cell lung cancer (NSCLC). The relevance of the lung field cancerization to the development of a particular subtype of NSCLC (i.e., adenocarcinoma compared with squamous cell carcinoma [SCC]), is still unknown, yet possible. Analyzing local and distant field of cancerization by analysis of the transcriptome of airway brushings from multiple sites independently for lung adenocarcinoma (yellow spots) and SCC (red spots) cases may shed light on events common or unique to the molecular pathogenesis of the two major subtypes of NSCLC. A “compartmental” approach coupled to a gradient or detailed molecular mapping method, which spans the tumor up to the nasal or buccal epithelium, to studying the field of cancerization may unravel biomarkers that can guide personalized prevention strategies suitable for each different NSCLC subtype. In addition, a comparison of the distant field cancerization in patients with cancer (left) to the expression patterns of the corresponding anatomical location in disease-free individuals (e.g., high-risk heavy smokers; right) would facilitate the development of efficacious markers for the detection of NSCLC. ADC = adenocarcinoma; miRNA = microRNA.