Longitudinal study of TP53 mutations in eight patients with potentially malignant oral mucosal disorders.
OBJECTIVE
In a previous cross-sectional study, the authors found a higher rate of TP53 mutation in oral lichen planus (OLP) than in hyperkeratosis. By analysing for TP53 mutations in serial samples from patients on long-term follow-up of their oral lesions, it was hoped to determine if these mutations were related to disease progression.


METHODS
Eight patients presenting with lesions diagnosed clinically as oral leukoplakia or lichen planus were followed from 2 to 12 years. Two to five samples of archival biopsy tissue were analysed from each patient by constant denaturant gradient gel electrophoresis for hotspots A, B, C, D and exon 6.


RESULTS
Four patients were diagnosed clinically as OLP: two of these were confirmed histopathologically, one was diagnosed as non-specific hyperkeratosis and one as cancer. Four patients had leukoplakia only, with a histopathological diagnosis of hyperkeratosis. Seven patients had TP53 mutations, three of them on repeated occasions. All five patients who developed squamous-cell carcinoma had mutations. Two of them had mutated pre-malignant lesions, and one of these previously had a non-mutated cancer. Three patients had two different primary cancers, only one of them mutated. One patient developed a mutated cancer 5 years after the last mutation-free biopsy. Of the cancer-free patients, a lesion regarded clinically as cancer-suspicious in one case was mutated, in another patient two OLP lesions were mutated, the third had five biopsies taken during 8 years, all non-mutated.


CONCLUSIONS
TP53 mutations may occur early or late in the development of oral squamous-cell carcinoma.
Ogmundsdóttir
H M
HM
Molecular and Cell Biology Laboratory, Icelandic Cancer Society, Iceland. helgaogm@hi.is
Hilmarsdóttir
H
H
Björnsson
J
J
Holbrook
W P
WP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics*; D017676:Lichen Planus, Oral / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53