J Lung Cancer.  2012 Jun;11(1):12-20. 10.6058/jlc.2012.11.1.12.

Molecular Pathogenesis of Non-Small Cell Lung Carcinomas

• Wistuba II

• KMID: 2199871
• DOI: http://doi.org/10.6058/jlc.2012.11.1.12

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.

Keyword

Lung neoplasms; Non-small-cell lung carcinoma; Adenocarcinoma; Squamous cell carcinoma; Epidermal growth factor receptor; Precancerous conditions

MeSH Terms

Adenocarcinoma
Biomarkers
Biology
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Chemoprevention
Humans
Hyperplasia
Lung
Lung Neoplasms
Numismatics
Precancerous Conditions
Receptor, Epidermal Growth Factor
Respiratory Mucosa
Receptor, Epidermal Growth Factor

Figure

• 

  Fig. 1 Paradigm changes in the classification of non-small cell lung carcinoma. Targetable abnormalities of multiple oncogenes, particularly mutations, translocations and gene amplifications have been recently discovered in both adenocarcinoma and squamous cell carcinoma histologies. Most abnormalities are referred to gene mutations, except EML4-ALK, KIF5B-RET and ROS1-FIG rearrangement and FGFR1 amplification (Amp).

• 

  Fig. 2 Sequential histological abnormalities involved in the pathogenesis of squamous cell carcinoma and adenocarcinoma of the lung. The mucosal changes in the large airways that precede invasive squamous cell carcinoma include: hyperplasia, squamous metaplasia, squamous dysplasia and carcinoma in situ. Dysplastic squamous lesions may be of different intensities: mild, moderate and severe. Atypical adenomatous hyperplasia (AAH) is considered a putative precursor of adenocarcinoma, particularly those with extensive lepidic pattern (former bronchioloalveolar [BAC] pattern). AAH is a discrete parenchymal lesion arising in the alveoli close to terminal and respiratory bronchioles.

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