Association between p53 mutation and clinicopathological features of non-small cell lung cancer.
Genetic alterations in exons 5-8 of the p53 gene, determined by single-strand conformation polymorphism and sequencing analyses, and the clinicopathological characteristics of 108 patients with non-small cell lung cancer were compared. Mutations in this gene were found in 37 of the 108 patients (34%): in 30% (23/76) of those with adenocarcinomas, 46% (12/26) of those with squamous cell, 33% (1/3) of those with large cell and 33% (1/3) of those with adenosquamous carcinomas. No associations between the incidence of p53 mutations and the histological or cytological subtypes of adenocarcinomas were found. The analysis of types of mutations, however, showed that GC transversion was relatively common in papillary and clara subtypes, whereas it accounted for only 17% at most of p53 mutations in tubular and bronchial surface epithelial cell subtypes of adenocarcinomas. Univariate analyses revealed that large tumor size, high nodal stage and positive vascular invasion of non-small cell lung cancers, and high nodal stage and high-grade nuclear atypia of adenocarcinomas were associated significantly with p53 mutations. Multivariate analyses showed that the tumor sizes of non-small cell lung cancer correlated with p53 mutations with marginal significance (P = 0.099) whereas nuclear atypia of adenocarcinomas correlated significantly (P = 0.028). No differences between the overall or relapse-free survival rates of patients with and without p53 mutations in non-small cell lung cancers or adenocarcinomas were found. These findings indicate that p53 mutations in adenocarcinomas of the lung are associated with the malignant phenotype of tumor cells, but not with patient survival.
Guang
S G
SG
Investigative Treatment Division, National Cancer Center Research Institute East, Chiba, Japan.
Ogura
T
T
Sekine
I
I
Yokozaki
M
M
Esumi
H
H
Kodama
T
T
Nagai
K
K
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001483:Base Sequence; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002467:Cell Nucleus / Q000648:ultrastructure; D003596:Cytosine; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D004848:Epithelium / Q000473:pathology; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006147:Guanine; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm; D006147:Guanine; D003596:Cytosine