Absence of p53 mutations in squamous carcinomas of the tongue in nonsmoking and nondrinking patients younger than 40 years.
BACKGROUND
Although carcinoma of the tongue usually occurs in patients older than 60 years, up to 4% of these tumors may occur in patients younger than 40 years. Many of the younger patients with this tumor have had no exposure or brief exposure to tobacco smoke or alcohol consumption, to which oral carcinoma is usually attributed. The molecular mechanism responsible for carcinogenesis in this group of patients is not known.


OBJECTIVE
To assess the role of p53 gene mutation in oral carcinogenesis in a group of patients younger than 40 years with squamous carcinoma of the tongue.


METHODS
Squamous carcinoma cells were isolated from paraffin blocks by microdissection. DNA extracted from these cells was tested for the presence of p53 mutations by polymerase chain reaction and single-stranded conformational polymorphism analysis. Mutations identified by this procedure were directly sequenced. Sections of the tumors were also stained using an immunoperoxidase immunohistochemical technique for expression of p53 protein.


METHODS
Eleven patients were selected on the basis of 2 criteria: presence of squamous cell carcinoma and age younger than 40 years. Six of the 11 patients had no history of measurable tobacco or alcohol exposure.


RESULTS
Two mutations were detected among 11 tumors by single-stranded conformational polymorphism analysis, one in exon 4 and a second in exon 7. The former mutation consisted of G:C to C:G (guanine:cytosine to cytosine:guanine) transition in codon 72 (CGC to CCC), which would have resulted in the substitution of a proline residue for arginine. With the immunoperoxidase immunohistochemical technique for p53 protein, strong, diffuse nuclear staining was observed only in this tumor. The second mutation was a G:C to A:T (guanine:cytosine to adenine:thymine) transition in codon 248 (CGG to CGA), which would have resulted in no amino acid change since both mutant and wildtype codon sequences encode arginine. Weaker and more variable anti-p53 immunostaining was noted in this and 4 other tumors. Five tumors were negative for p53 protein by the immunoperoxidase immunohistochemical technique.


CONCLUSIONS
Our results suggest that p53 gene mutations are less frequent in squamous carcinomas occurring in nonsmoking young patients who do not drink alcohol than in young smokers or in the general population. Paucity of p53 mutations may be explained by the absence of exposure to tobacco smoke or alcohol. These data leave unanswered the question of the molecular mechanism responsible for oral carcinogenesis in this group of patients and suggest that this group may be a suitable population in which to study genetic susceptibility to aerodigestive carcinoma isolated from the confounding factors of tobacco and alcohol exposure.
Sorensen
D M
DM
Department of Otolaryngology--Head and Neck Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Lewark
T M
TM
Haney
J L
JL
Meyers
A D
AD
Krause
G
G
Franklin
W A
WA
D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000235:genetics*; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53