Evaluation of p53 Gene Mutation and Loss of Heterozygosity of 3p, 9p and 17p in Precancerous Lesions of 29 Lung Cancer Patients

To assess the multiple steps involved in carcinogenesis we evaluated p53 gene mutation frequencies, and loss of heterozygosity (LOH) of chromosomes 3p, 9p and 17p in hyperplasia, squamous metaplasia, dysplasia, squamous cell carcinoma in-situ and early squamous cell carcinoma of the bronchial epithelium, using immunohistochemical, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and microsatellite analysis. Overexpression of p53 oncoprotein was observed in 31 % of mild dysplasia, 50% of moderate and 67% of severe dysplasia. Mutation of the p53 gene, however, was confirmed only in 2 severe dysplasias. LOH of 3p, 9p and 17p were detected in 8% of mild and 6% of moderate dysplasias. Among other types of bronchial lesions, two columnar cell hyperplasias showed LOH of 3p and 17p, respectively. These results suggest that LOH of 3p or 9p may be a rare but early event in the development of squamous cell carcinoma of the lung. In particular, deletion of 3p21.3 is a relatively common event in premalignancy. The results also suggest that p53 gene abnormalities occur during the following stage of carcinogenesis.