Expression of the p53 Family in Lung Cancer

Abstract

Background: p53 is mutated in about 50% of various malignant diseases including lung cancer. The p53 family consists of p53, p73 and p63. Although transactivating protein isoforms display p53-like functions, the ΔNp73 or ΔNp63 isoforms act toward p53 in a dominantly negative way. The aim of this study was to detect p53, ΔNp73 and ΔNp63 expressions in lung cancer and to evaluate the relationship between the expression levels of the proteins and the prognosis of patients with resectable lung cancer. Materials and Methods: Immunohistochemistry was employed to analyze the protein expression of p53, ΔNp73 and ΔNp63 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients. The correlation among the expression levels of p53, ΔNp73 and ΔNp63, clinical variables and survival outcome was analyzed. Results: Positive expressions of p53, ΔNp73 and ΔNp63 were detected in the tumor cells in 52, 77 and 44 of the 132 patients, respectively (39.4%, 58.3% and 33.3%) with lung cancer. The incidence of p53 positive expression was 54.5% and 27.6% in patients with squamous cell carcinoma and adenocarcinoma, respectively (p=0.03). The incidence of a positive expression of ΔNp73 was 64.5% and 43.6% in male and female patients, respectively (p=0.03). The incidence of ΔNp63 positive expression was 68.2% and 15.8% in the patients with squamous cell carcinoma and adenocarcinoma, respectively (p<0.0001). The expressions of p53 and ΔNp63 were not found to significantly affect survival. However, lung cancer patients with a positive ΔNp73 expression had a poorer prognosis than those with a negative ΔNp73 expression. In addition, multivariate analysis indicated that a positive expression of ΔNp73 was a significantly independent factor for predicting a poor prognosis (p<0.0001, risk ratio=3.38). Conclusion: Clinical evidence that the p53 family is frequently overexpressed in lung cancer specimens, especially ΔNp63 in squamous cell carcinoma, was provided. The expression of ΔNp73 may be a useful marker for predicting a poor prognosis in resectable lung cancer. Understanding how groups of lung cancer cell genes are coordinately expressed in response to physiological, immunological and micro-environmental stimuli remains an important goal. A better understanding of the gene expression profiles of tumors may help to identify molecular targets, such as ΔNp73, for effective therapy.