Chromosome instability predicts the progression of premalignant oral lesions.
OBJECTIVE
One of the main problems in reducing the incidence of oral squamous cell carcinoma (OSCC) is the inability to appropriately deal with leukoplakia. Accurately identifying lesions which will progress to malignancy is currently not possible. The present study aims to establish the value of chromosome instability (CI) detection by DNA image cytometry and FISH analysis for prognosis and monitoring of oral leukoplakia.


METHODS
For this purpose, we included from our archives 102 oral leukoplakia cases, which had been diagnosed between 1991 and 2008. Patient follow-up data were collected and the histopathological diagnosis was revised. CI assessment was carried out on paraffin-embedded tissue sections using both DNA image cytometry (ICM) and dual target FISH for chromosomes 1 and 7.


RESULTS
16 of 102 Patients developed carcinoma in situ or OSCC. Both detection methods were found to yield prognostic information independent of the histopathological diagnosis. CI was a strong individual marker of progression, with hazard ratios (HRs) of 7.2 and 6.8 for ICM and FISH respectively. Moreover, this approach seems suitable for monitoring lesions over time (especially ICM). Combining histopathology and CI enables subdivision of patients into three risk groups, with different probabilities of malignant progression.


CONCLUSIONS
CI detection seems a reliable method for risk assessment of oral premalignancies and its application may contribute to a better risk-counselling and appropriate treatment regimen or watchfull-waiting approach of patients.
Department of Oral and Maxillofacial Surgery, Radboud University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Pathology, Radboud University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
T J H
TJ
Siebers
V E
VE
Bergshoeff
I
I
Otte-Höller
B
B
Kremer
E J M
EJ
Speel
J A W M
JA
van der Laak
M A W
MA
Merkx
P J
PJ
Slootweg
D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D043171:Chromosomal Instability; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods
D004273:DNA, Neoplasm
Chromosome instability; FISH; Head and neck cancer; Leukoplakia; Oral cancer; Oral premalignancies; Ploidy analysis