P53 immunohistochemistry can identify bronchial dysplastic lesions proceeding to lung cancer: a prospective study

Dysplasia is an important step in bronchial carcinogenesis and smokers present 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 dysplastic areas could be a predictive marker of the development of lung cancer, we investigated p53 overexpression in 22 bronchial dysplastic lesions obtained by fibrebronchoscopy from heavy smokers who were not diagnosed as having 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 patients and 3 in 13 (23%) patients with p53-negative lesions. Lung cancer occurred in all seven patients with dysplastic lesions showing >10% p53 positive nuclei. The positive predictive value of p53 immunostaining for lung cancer was 78%. The negative predictive value of p53 was 77%. p53 staining was not detected in squamous metaplasia lesions without atypia and in normal bronchial epithelium. Our findings provide evidence that p53-overexpression in bronchial dysplastic areas may be a clinically useful marker for identifying patients proceeding to, at least, squamous cell carcinoma and, in addition, may facilitate the detection of occult tumours.