p53 immunohistochemistry can identify bronchial dysplastic lesions proceeding to lung cancer: a prospective study

Dysplasia is an important step in bronchial carcinogenesis and smokers pres ent more dysplastic lesions than nonsmokers. These lesions not always lead to malignancy, so there is a need for additional, preferentially objective, diagnostic markers. To verify whether immunohistochemical overexpression of p53 protein in dysp lastic areas could be a predictive marker of the development of lung cancer , we investigated p53 overexpression in 22 bronchial dysplastic lesions obt ained by fibrebronchoscopy from heavy smokers who were not diagnosed as hav ing lung cancer and were followed for a 4-yr period. Nine (41%) lesions showed p53-positivity, Seven lung cancers (78%), mostly squamous cell carcinomas, were detected within the follow-up in these patie nts and 3 in 13 (23%) patients with p53-negative lesions. Lung cancer occur red in all seven patients with dysplastic lesions showing >10% p53 positive nuclei, The positive predictive value of p53 immunostaining for lung cance r was 78%, The negative predictive value of p53 was 77%, p53 staining was n ot detected in squamous metaplasia lesions without atypia and in normal bro nchial epithelium. Our findings provide evidence that p53-overexpression in bronchial dysplast ic areas may be a clinically useful marker for identifying patients proceed ing to, at least, squamous cell carcinoma and, in addition, may facilitate the detection of occult tumours.