p53 nuclear immunostaining and gene mutations in non-small-cell lung cancer and their effects on patient survival

Abstract

Background : p53 gene mutations are known to occur in about half of all non-small-cell lung cancer (NSCLC) cases. Mutations of the p53 gene usually but not always lead to an increased half life of the p53 protein, and result in a nuclear accumulation of protein which can be detected by immunohistochemistry (NC). Controversy still exists as to whether the presence of an aberration of the p53 gene or protein is a poor prognostic indicator in patients with NSCLC. Patients and methods : DNA samples and paraffin blocks were obtained from 129 patients of 143 consecutive patients who underwent a pulmonary resection during a 22-month period from July 1991 to April 1993. Mutations of the p53 gene occurring at exons 5–8 were detected by a polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) assay, while the nuclear accumulation of the p53protein was detected by immunohistochemistry. Results : Of the patients studied, 35% had mutations and 54% showed overexpression, when we defined a positive case as being one in which more than 10% of the tumor cell nuclei were stained. There was a 59.5% concordance between the p53 gene mutations and p53 imniunopositivity. p53 immunopositivity in adenocarcinoma and any p53 abnormality (i.e. p53 immunopositivity and/or mutation) in adenocarcinoma were a poor prognostic indicator. However, Cox's proportional hazards model indicated that the stage was the only significant prognostic factor. Conclusion : p53 immunopositivity and mutations of the p53 gene are frequently seen in NSCLC. They are considered to be mutually related but may sometimes represent a different aspect of p53 abnormality. p53 alteration may be a poor prognostic indicator only in a subset of patients with NSCLC, especially for adenocarcinoma.