WIDELY DISPERSED P53 MUTATION IN RESPIRATORY EPITHELIUM - A NOVEL MECHANISM FOR FIELD CARCINOGENESIS

Individuals with one aerodigestive tract malignancy have a high incide nce of second primary aerodigestive tumors. The mechanism for this fie ld effect has not been determined. We studied an individual with wides pread dysplastic changes in the respiratory epithelium but no overt ca rcinoma, The entire tracheobronchial tree obtained at autopsy was embe dded in paraffin, and bronchial epithelial cells were isolated by micr odissection, DNA extracted from the microdissected cells was analyzed for point mutations in the p53 tumor suppressor gene. A single, identi cal point mutation consisting of a G:C to T:A transversion in codon 24 5 was identified in bronchial epithelium from 7 of 10 sites in both lu ngs. Epithelium at sites containing the p53 mutation was morphological ly abnormal, exhibiting squamous metaplasia and mild to moderate atypi a. No invasive tumor was found in the tracheobronchial tree or any oth er location, Cells from peripheral blood, kidney, liver, and lymph nod e exhibited no abnormality in the p53 gene, The widespread presence of a single somatic p53 point mutation in the bronchi of a smoker sugges ts that a single progenitor bronchial epithelial clone may expand to p opulate broad areas of the bronchial mucosa-a novel mechanism for fiel d carcinogenesis in the respiratory epithelium that may be of importan ce in assessing individuals for risk of a second primary tumor as well as in devising effective strategies for chemoprevention of lung cance r.