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Molecular Oncology, Markers, Clinical Correlates |
Departments of Thoracic Surgery [T. M.] and Internal Medicine [M. O.], Aichi Cancer Center Hospital, and Divisions of Epidemiology [N. H.] and Prevention and Molecular Oncology [T. T.], Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
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, 
2
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.
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