DNA content as a prognostic marker in patients with oral leukoplakia.
BACKGROUND
Oral leukoplakia may develop into squamous-cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia.


METHODS
We identified 150 patients with oral leukoplakia that was classified as epithelial dysplasia and measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Biopsy specimens obtained at annual follow-up visits were graded histologically and classified with respect to DNA content in a blinded fashion. Disease-free survival was assessed in relation to DNA ploidy and the histologic grade. The mean duration of follow-up was 103 months (range, 4 to 165).


RESULTS
Among 150 patients with verified epithelial dysplasia, a carcinoma developed in 36 (24 percent). Of the 150 patients, 105 (70 percent) had diploid (normal) lesions, 20 (13 percent) had tetraploid (intermediate) lesions, and 25 (17 percent) had aneuploid (abnormal) lesions at the time of the initial diagnosis. A carcinoma developed in 3 of the 105 patients with diploid lesions (3 percent), as compared with 21 of the 25 patients with aneuploid lesions (84 percent), yielding a negative predictive value of 97 percent with respect to the diploid lesions and a positive predictive value of 84 percent with respect to the aneuploid lesions. Carcinoma developed in 12 of 20 patients with tetraploid lesions (60 percent). The mean time from the initial assessment of the DNA content to the development of a carcinoma was 35 months (range, 4 to 57) in the group with aneuploid lesions and 49 months (range, 8 to 78) in the group with tetraploid lesions (P=0.02). The cumulative disease-free survival rate was 97 percent among the group with diploid lesions, 40 percent among the group with tetraploid lesions, and 16 percent among the group with aneuploid lesions (P<0.001).


CONCLUSIONS
The DNA content in cells of oral leukoplakia can be used to predict the risk of oral carcinoma.
Sudbø
J
J
Department of Pathology, Norwegian Radium Hospital and University of Oslo. jon.sudbo@rh.uio.no
Kildal
W
W
Risberg
B
B
Koppang
H S
HS
Danielsen
H E
HE
Reith
A
A
D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D004273:DNA, Neoplasm / Q000032:analysis*; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics; D011003:Ploidies; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers