Comparative evaluation of genetic assays to identify oral pre-cancerous fields.
BACKGROUND
Oral squamous cell carcinomas often develop in a pre-cancerous field, defined as mucosal epithelium with cancer-related genetic alterations, and which may appear as a clinically visible lesion. The test characteristics of three genetic assays that were developed to detect pre-cancerous fields were investigated and compared to histology.


METHODS
In total, 10 pre-cancerous fields that were not visible at clinical inspection and gave rise to malignant transformation based on an identical TP53 mutation in tumor and mucosal epithelium in the surgical margin, as well as 10 normal oral mucosa specimens were analyzed for numerical chromosomal changes with multiplex ligation-dependent probe amplification (MLPA), for loss of heterozygosity (LOH), with microsatellite PCR and for DNA index alterations with DNA image analysis.


RESULTS
No alterations were detected in normal tissue by either of the assays. Both MLPA and LOH assays detected all pre-cancerous fields. DNA cytometry identified aneuploidy in four of 10 pre-cancerous fields, while the corresponding tumors that developed in these fields were shown to be aneuploid.


CONCLUSIONS
Both the MLPA and LOH assay seem suitable for screening pre-cancerous fields in subjects at high risk for oral cancer even in the absence of clinically abnormal appearing oral mucosa. Measurements of DNA index might be valuable to determine the time to progression.
Bremmer
Jantine F
JF
Department of Oromaxillofacial Surgery and Oral Pathology, VU University Medical Center, Amsterdam, the Netherlands.
Braakhuis
Boudewijn J M
BJ
Brink
Arjen
A
Broeckaert
Mark A M
MA
Beliën
Jeroen A M
JA
Meijer
Gerrit A
GA
Kuik
Dirk J
DJ
Leemans
C René
CR
Bloemena
Elisabeth
E
van der Waal
Isaäc
I
Brakenhoff
Ruud H
RH
D000782:Aneuploidy; D004252:DNA Mutational Analysis; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics*; D019656:Loss of Heterozygosity; D025202:Molecular Diagnostic Techniques; D009062:Mouth Neoplasms / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D011230:Precancerous Conditions / Q000235:genetics*; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53