Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis.

There is great controversy as to whether alteration of the p53 gene adversely affects survival of non-small cell lung cancer patients. The aim of this study was to qualitatively review the association between p53 alterations and patient outcome by reviewing published papers. Forty-three articles were used. Survival difference was combined by use of the DerSimonian-Laird method. p53 alteration was either detected as overexpression by the protein studies or as mutation by the DNA studies. The incidence of p53 alteration in DNA studies (381 of 1031; 37%) was lower than that in protein studies (1725 of 3579; 48%; P < 0.0001, chi2 test). The incidence of p53 overexpression and mutation in adenocarcinoma (36 and 34%) was significantly lower than that in squamous cell carcinoma (54 and 52%; P < 0.0001). Combined survival differences at 5 years (survival in patients with alteration minus that in patients without alteration) by protein and DNA studies were -9.1% (P = 0.0091) and -22.0% (P = 0.0026), respectively. The negative prognostic effect of p53 alteration was highly significant in patients with adenocarcinoma [-21.8% at 5 years (P = 0.0000039) by protein studies and -48.0% (P = 0.000031) by DNA studies] but not in patients with squamous cell carcinoma [-15.6% (P = 0.4241) by protein studies and 2.0% (P = 0.8864) by DNA studies]. In the light of these results, p53 alteration was a significant marker of poor prognosis in patients with pulmonary adenocarcinoma. Whether p53 alteration also provides information that can alter treatment decisions should be asked in clinical trials.