Molecular pathology of lung cancer

Lung cancer is classified into two major clinicopathological groups, namely small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Squamous cell carcinoma, adenocarcinoma and large cell carcinoma are the major histological types of NSCLC. Large cell carcinoma probably represents poorly differentiated variants of the other NSCLC types. As with other epithelial malignancies, lung cancers are believed to arise after a series of progressive pathological changes (preneoplastic lesions) in the bronchial epithelium. However, this sequence has been well established only for squamous cell carcinoma. Many mutations, especially involving recessive oncogenes, have been described in clinically evident lung cancer. While some of these are common to all lung cancer types, some are more frequent in specific tumour types. For risk assessment and very early lung cancer detection it would be helpful to know about molecular events in the respiratory epithelial molecule preceding the development of lung carcinoma. Preneoplasia and the development of lung cancer Lung cancers are believed to arise after a series of progressive pathological changes (preneoplastic or precursor lesions) in the respiratory mucosa. While the sequential preneoplastic changes have been defined for centrally arising squamous carcinoma (Fig. 20.1), they have been poorly documented for the other cell types. Epithelial changes in the large airways that may precede or accompany invasive squamous cell carcinoma include hyperplasia (basal cell hyperplasia and goblet cell hyperplasia), squamous metaplasia, squamous dysplasia and carcinoma in situ (CIS).