Frequent expression of p53 protein without mutation in the atypical epithelium of human bronchus.

We investigated the correlation between p53 protein levels and mutations in the p53 gene of atypical bronchial epithelium (ABE). Protein levels were analyzed by immunohistochemistry, whereas mutations were assessed by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and direct sequencing. A total of 78 formalin-fixed, paraffin-embedded bronchial biopsy specimens that had been diagnosed to be ABE were retrieved from the archives and examined. p53 protein was expressed in 44 of the 78 (56%) specimens overall. However, when pathologically classified, 38% of hyperplasias, 58% of metaplasias, and 73% of dysplasias were positive, indicating that an increased frequency of p53 expression correlated with the severity of ABE (P = 0.042). Among the 44 specimens that expressed p53 protein, 40 (91%) did not reveal mutations by PCR-SSCP. In the four specimens with abnormal PCR-SSCP bands, p53 gene mutation was identified by direct sequencing and revealed the same point mutation at codon 248 (CGG-to-CTG transversion) of exon 7 in all four specimens. These four specimens were dysplasias derived from patients with lung cancer. p53 protein expression in ABE was associated with the wild-type gene in most cases; therefore, wild-type p53 protein expressed in ABE might have a protective function from lung carcinogenesis, and mutation of p53 gene may be a late event in the sequential steps of lung carcinogenesis.