Accumulative increase of loss of heterozygosity from leukoplakia to foci of early cancerization in leukoplakia of the oral cavity.
BACKGROUND
Oral leukoplakia is a premalignant lesion, but the genetic changes in the foci of early cancerization in leukoplakia have not been studied.


METHODS
Loss of heterozygosity (LOH) was successively investigated in 13 cases in the leukoplakia and foci of early cancerization in the same leukoplakia. The authors microdissected both lesions, and 33 microsatellite markers at 14 chromosomal loci were examined by a polymerase chain reaction-based microsatellite assay.


RESULTS
Loss of heterozygosity detected in the leukoplakia was identically observed in the foci of early cancerization in leukoplakia in 11 of 13 cases, and in 2 cases allelic divergence was observed. Loss of heterozygosity occurred even in the leukoplakia with high frequency at 9p21 (66.7%), 3p14-25 (61.5%), 4q31-32 (45.5%), and 17p12-14 (44.4%). The foci of early cancerization in leukoplakia showed accumulative increase of LOH at these and other loci. Loss of heterozygosity at 5q21-23 was found to have significant difference between the leukoplakia and the foci of early cancerization in leukoplakia (P = 0.0137, Fisher exact test). Microsatellite instability was observed at low level in three cases. The mean value of fractional allelic loss in the leukoplakia differed significantly from that in the foci of early cancerization in leukoplakia (0.02 < P < 0.05, Student t test).


CONCLUSIONS
The high incidence of LOH in the leukoplakia indicated premalignant potentiality of this lesion and that accumulative increase of LOH from leukoplakia to foci of early cancerization in leukoplakia might play a significant role in the cancerization of leukoplakia. Comparison of LOH between the leukoplakia and the foci of early cancerization in leukoplakia suggested that these two lesions were derived from a common clone.
Jiang
W W
WW
Labs at Molecular Pathology, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. wwopat@dent.tmd.ac.jp
Fujii
H
H
Shirai
T
T
Mega
H
H
Takagi
M
M
D000368:Aged; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*
D004273:DNA, Neoplasm