Molecular Pathology of Precursor and Pre-invasive Lesions

Part of the Molecular Pathology Library book series (MPLB, volume 6)


This chapter discusses the molecular biology of pulmonary pre-invasive lesions. Most is known about the changes found in squamous dysplasia/carcinoma in situ of the bronchial epithelium. Many of these molecular changes are probably induced by tobacco carcinogens. The loss of tumour suppressor gene (TSG) function is probably more important than oncogene activation in promoting consequent growth activation. Loss of TSG function may be due to mutation, deletion, epigenetic silencing or activation of inhibitory mechanisms. Important TSGs include P53, P16 and others on chromosome 3. There is also molecular evidence, in squamous dysplasia and squamous carcinoma in situ (SD/CIS), of significant alterations in the other factors considered the Hallmarks of Cancer, namely evasion of apoptosis, limitless replicative potential, sustained angiogenesis and tissue invasion and metastasis. Rather less is known about the molecular changes found in atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) although the same five characteristics of malignant change all show, to a varying degree, alteration in molecular pathways relevant to each. In this pathway of carcinogenesis, oncogene activation, leading to growth promotion has a greater importance with epidermal growth factor receptor or KRAS mutation potentially important. Many of the same mechanisms of TSG inactivation seen in SD/CIS appear active in at least some cases of AAH or AIS. Virtually nothing is known about the molecular biology of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.


Epidermal Growth Factor Receptor Idiopathic Pulmonary Fibrosis Epidermal Growth Factor Receptor Mutation KRAS Mutation Invasive Adenocarcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Pathology, Aberdeen Royal InfirmaryAberdeen University Medical SchoolAberdeenUK

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