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Molecular Pathology of Precursor and Pre-invasive Lesions

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Molecular Pathology of Lung Cancer

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

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Abstract

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.

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Authors and Affiliations

  1. Department of Pathology, Aberdeen Royal Infirmary, Aberdeen University Medical School, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK

    Keith M. Kerr MD, FRCPath

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  1. Keith M. Kerr MD, FRCPath
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  1. , Department of Pathology, The Methodist Hospital, 6565 Fannin Street, Houston, 77030, Texas, USA

    Philip T. Cagle

  2. Health Science Center at Tyler, Department of Pathology, The University of Texas, 11937 US Highway 271, Tyler, 75708, Texas, USA

    Timothy Craig Allen

  3. , Department of Pathology, Mount Sinai Medical Center, 1 Gustave L. Levy Place, New York, 10029, New York, USA

    Mary Beth Beasley

  4. , Department of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, 02115, Massachusetts, USA

    Lucian R. Chirieac

  5. Medical Center, Department of Pathology, University of Pittsburgh, 200 Lothrop St. - PUH C608, Pittsburgh, 15213, Pennsylvania, USA

    Sanja Dacic

  6. Medical Center, Department of Pathology &, Columbia University, 630 W. 168th Street VC-14-215, New York, 10032, New York, USA

    Alain C. Borczuk

  7. Medical School, Department of Pathology, Aberdeen University, Foresterhill, Aberdeen, Scotland, AB25 2ZD, United Kingdom

    Keith M. Kerr

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Kerr, K.M. (2012). Molecular Pathology of Precursor and Pre-invasive Lesions. In: Cagle, P., et al. Molecular Pathology of Lung Cancer. Molecular Pathology Library, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3197-8_6

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