p53 Immunostaining Positivity Is Associated With Reduced Survival and Is Imperfectly Correlated With Gene Mutations in Resected Non-small Cell Lung Cancer

A Preliminary Report of LCSG 871

¹ From the Simmons Cancer Center, University of Texas South-western Medical Center, Dallas
² From the Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan
³ From Hokkaido University School of Dentistry, Department of First Oral Surgery, Sapporo, Japan
⁴ From Johns Hopkins University School of Medicine, Baltimore
⁵ From Memorial Sloan Kettering Cancer Center, New York
⁶ From the Department of Pathology, Illinois Masonic Medical Center, Chicago
⁷ From University of California at Los Angeles

We investigated the correlation of p53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent as part of Lung Cancer Study Group (LCSG) 871. Our previous studies showed that only a subset of p53 mutations in lung cancers result in overexpression. In addition, protein overexpression has been described in the absence of mutation. Therefore, we determined both p53 protein overexpression (by immunostaining) and p53 and ras gene mutations (by single-strand conformation polymorphism and DNA sequencing) in this set of resected tumor specimens. Clinical follow-up data were available for 75 cases. Of the studied patients, 64% showed p53 overexpression and 51% had mutant p53 sequences; however, the concordance rate was only 67%. There was a negative survival correlation with positive p53 immunostaining (p=0.05), but not with the presence of gene mutations (p=0.62) in this group of patients. Overexpression of p53 protein determined by immunostaining may contribute to adverse outcome due to the ability of p53 to act as a dominant oncogene, or alternatively, overexpression may reflect ongoing DNA damage in the tumor as a marker for a more aggressive behavior. When adjusted for stage, age, and gender by multivariate analysis, however, there was no independent impact of p53 overexpression on survival.