Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients

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Abstract
According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bronchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-stained sections using a high-performance digitised image analyser. Archival material from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected, including 16 central tumours (mainly squamous cell carcinomas) and 19 peripheral tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour from extrathoracic primary sites. Of the NSCLCs, 31/35 (89%) were aneuploid, as were 60% of the metastases from extrathoracic sites. Multiple, focal areas of preneoplasia or preinvasive carcinoma were present in the selected cases. The lesions ranged in severity from hyperplasia through metaplasia and dysplasia to carcinoma in situ. Aneuploid preinvasive lesions were not noted in association with the four diploid tumours but were present only when the accompanying NSCLC was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic lesions were more frequent in the peripheral parts of the lung (bronchioles or alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy increased with progressive severity of morphological change. Aneuploidy was not found in preinvasive lesions accompanying the five metastatic cases. Our findings provide strong support for the concept of field cancerisation.