Zm. Guo et al., Allelic losses in OraTest-directed biopsies of patients with prior upper aerodigestive tract malignancy, CLIN CANC R, 7(7), 2001, pp. 1963-1968
Genetic alterations at critical chromosome loci have been shown to be predi
ctors of the progression of oral premalignancy-to-invasive cancer. We obtai
ned a unique group of oral biopsies, initially collected during a prospecti
ve study designed to test the ability of OraTest (toluidine blue), to ident
ify recurrent oral neoplastic lesions in patients with definite therapy for
head and neck or upper aerodigestive tract (UADT) cancer. A total of 46 ca
ses, including 13 squamous cell carcinoma (SCC), 11 carcinoma-in situ or dy
splasia, and 22 morphologically normal oral biopsies, were analyzed for los
s of heterozygosity (LOH) at 9p21, 3p21, and 17p13(TP53) by microsatellite
analysis. LOH at one or more tested markers in at least one biopsy was dete
cted in 76% (35 of 46) cases, All of the SCC and carcinoma-ill situ cases s
howed LOH, and, strikingly, more than one-half (69%, 13 of 22) of morpholog
ically normal epithelia also harbored LOH in at least one tested marker. Th
e most frequent LOH was found on chromosome 9p21 (69 %, 31 of 45). LOH was
observed at 3p21, 17p13(TP53), or in multiple chromosomal arms significantl
y more often in SCC than in normal epithelia, In the majority of cases, two
oral biopsies, one from an OraTest-staining positive area and another from
a negative area adjacent to the stain, were collected. Among 25 LOH positi
ve cases with two biopsies, identical allelic losses were confirmed between
stained and nonstained biopsies in 16 cases. In the remaining nine cases w
ith discordant LOH patterns between two biopsies, eight cases showed LOH at
more genetic loci in OraTest-stained areas. Our data confirm that clonal g
enetic alterations, especially 9p21 deletion, are often present in the oral
epithelia of patients with previous UADT malignancy and, combined with pre
vious studies, suggest that genetic analysis will help stratify patients at
risk of developing a secondary oral cancer. In addition to detecting cance
r, our study suggests that OraTest can detect clinically occult lesions in
the progression pathway to oral cancer.