Oral lesion progression markers validated, discovered

By Sarah Guy, medwireNews Reporter

Loss of heterozygosity (LOH) can reliably differentiate between individuals with premalignant oral lesions who are likely to progress to oral carcinoma, and those who are not, show study results.

Miriam Rosin (BC Cancer Agency, Vancouver, British Columbia, Canada) and colleagues' findings validate a LOH model reported in 2000 involving chromosome regions 3p14.2 and 9p21, and show that LOH in another two loci on 4q26 and 17p11.2 improve risk prediction further.

"These extraordinarily well-done and well-analyzed studies underscore the use of LOH in community-based risk assessment, and, perhaps, in patient therapeutic and prevention stratification schemes," comments Webster Canenee (University of California, San Diego, USA), a co-author of the 2000 study, in an accompanying editorial.

Rosin and team analyzed LOH markers in 296 patients who presented with oral dysplastic lesions between 1997 and 2007, and were followed up for a median of 45 months.

Only 1% of patients who retained 3p and 9p - the low-risk pattern from the 2000 study - developed oral carcinoma, compared with 97.5% of those with the 2000 high-risk pattern of 3p and/or 9p LOH. Indeed, the high-risk pattern was associated with a significant 22.6-fold increase in progression risk compared with the low-risk pattern.

In recursive partitioning analysis, the researchers identified 9p, 17p, and 4q as covariates for an updated classification model where retention of 9p was considered low risk for progression, 9p LOH alone or with either 17p LOH or 4q LOH was considered intermediate risk, and LOH on all three arms was considered high risk.

The team reports 5-year cancer progression rates of 3.1%, 16.3%, and 63.1% for the low-, intermediate-, and high-risk groups, respectively, using this model.

Furthermore, compared with low-risk lesions, intermediate- and high-risk lesions were a respective 11.6 and 52.1 times more likely to progress - both significant findings.

After classifying the 2000 cohort into these updated risk groups, results followed a similar trend, with 3.4-fold and 11.2-fold increased risk for progression in intermediate- and high-risk lesions compared with low-risk ones, report the researchers in Cancer Prevention Research.

This work "has direct implications for standard care in the community setting, identifying low-risk individuals who are not in need of aggressive monitoring or treatment," remark Mark Lingen (University of Chicago Medical Center, Illinois, USA) and Eva Szabo (National Cancer Institute, Bethesda, Maryland, USA) in a second related editorial.

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