Am. J. Respir. Crit. Care Med., Vol 150, No. 6, 12 1994, 1667-1671.
Exon 8 mutation of p53 gene associated with nodal metastasis in non- small-cell lung cancer
LN Lee, JY Shew, JC Sheu, YC Lee, WC Lee, MT Fang, HF Chang, CJ Yu, PC Yang and KT Luh
National Taiwan University Hospital and Institute of Biomedical Science, Academia Sinica, Taipei.
The epidemiologic characteristics of lung cancer in Taiwan differ from
those in other parts of the world in low male-to-female ratio, the high
percentage of adenocarcinoma, and the relatively high percentage of
nonsmokers who are victims. To investigate possible correlation between p53
gene alteration and the unique characteristics of lung cancer here, p53
gene status of 36 patients with primary, resected non-small-cell lung
cancer (NSCLC) was studied by directly sequencing the cDNA of the p53 gene,
then acquiring clinical and pathologic data to correlate p53 gene status
with clinical parameters and pathologic staging. Missense mutations were
present in 42% (15 of 36) of patients with NSCLC, including 42% (10 of 24)
with adenocarcinomas, and 45% (five of 11) with squamous cell carcinomas.
The frequency of p53 mutation was 50% in smokers and 29% in nonsmokers (p =
0.355). The mutation occurred most frequently in exon 8 (56%), and G:C to
A:T transitions in non-CpG or CpG sites were the most commonly observed
base changes (56%). These findings differ from the high prevalence of G to
T transversion found in previous reports. The frequency of metastasis in
hilar and mediastinal lymph nodes was significantly higher in tumors with
p53 mutations. The association with nodal stage was strong for mutations
within exon 8, but it was less apparent for mutations in other exons
probably because of the small number. This study suggests that p53 gene
missense is common in NSCLC in Taiwan, but smoking is probably not the sole
contributing factor. More interestingly, p53 gene mutations, especially
those in exon 8, may be associated with regional nodal metastasis.
