Association between p53 immunostaining and cigarette smoking in squamous cell carcinoma of the esophagus.
BACKGROUND
It is generally accepted that cigarette smoking is closely associated with esophageal squamous cell carcinoma. This study investigated the molecular targets of cigarette smoke in carcinogenesis of the esophagus.


METHODS
Seventy-four patients with esophageal squamous cell carcinoma (SCC) were grouped according to daily cigarette consumption: heavy smoking group (group H) (n = 26), moderate smoking group (group M) (n = 39) and non-smoking group (group N) (n = 9). We compared p53 and retinoblastoma (RB) expression among the three groups by immunohistochemistry. In addition, fresh tumor tissues from 30 smokers with esophageal SCC were tested for p53 mutations in exons 5-8 by direct sequencing.


RESULTS
Staining for the p53 product was positive in 65.4% of group H, 38.5% of group M and 44.4% of group N. The frequency of positive staining in the group H was significantly higher than in group M (p = 0.033) and in group M + group N (p = 0.034). The difference with respect to the frequency of overexpression of RB was not significant. The patterns of p53 base-pair mutations in direct sequencing study were of five types, most commonly G:C to T:A transversion (35.3%).


CONCLUSIONS
Our study suggests that one of the molecular targets of cigarette smoke is the p53 gene. The pattern of p53 point mutations involved a wide range of base-pair changes.
Mizobuchi
S
S
Department of Surgery II, Kochi Medical School, Japan. mizoshun@kochi-ms.ac.jp
Furihata
M
M
Sonobe
H
H
Ohtsuki
Y
Y
Ishikawa
T
T
Murakami
H
H
Kurabayashi
A
A
Ogoshi
S
S
Sasaguri
S
S
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53