P53 NUCLEAR IMMUNOSTAINING AND GENE-MUTATIONS IN NON-SMALL-CELL LUNG-CANCER AND THEIR EFFECTS ON PATIENT SURVIVAL

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 u sually but not always lead to an increased half life of the p53 protei n, and result in a nuclear accumulation of protein which can be detect ed by immuno-histochemistry (IHC). Controversy still exists as to whet her the presence of an aberration of the p53 gene or protein is a poor prognostic indicator in patients with NSCLC. Patients and methods: DN A samples and paraffin blocks were obtained from 129 patients of 143 c onsecutive patients who underwent a pulmonary resection during a 22-mo nth period from July 1991 to April 1993. Mutations of the p53 gene occ urring at exons 5-8 were detected by a polymerase chain reaction (PCR) /single strand conformation polymorphism (SSCP) assay, while the nucle ar accumulation of the p53 protein was detected by immunohistochemistr y. 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 immunopositivity. p53 immunopositivity in adenocarcinoma and any p53 abnormality (i.e. p 53 immunopositivity and/or mutation) in adenocarcinoma were a poor pro gnostic indicator. However, Cox's proportional hazards model indicated that the stage was the only significant prognostic factor.Conclusions : p53 immunopositivity and mutations of the p53 gene are frequently se en in NSCLC. They are considered to be mutually related but may someti mes represent a different aspect of p53 abnormality. p53 alteration ma y be a poor prognostic indicator only in a subset of patients with NSC LC, especially for adenocarcinoma.