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Molecular markers may predict which oral lesions progress to cancer
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Researchers identified a group of molecular markers that they believe can help clinicians determine whether low-grade oral premalignant lesions are at a high risk for progression to oral cancer.
Nearly 300,000 new cases of oral squamous cell carcinoma are identified worldwide each year, and the ability to detect oral cancers in the premalignant stage could have a significant effect on patient outcomes, the researchers wrote.
In 2000, Miriam Rosin, PhD, director of the oral cancer prevention program at the British Columbia Cancer Agency in Vancouver, and colleagues evaluated oral premalignant lesion samples in which cancer progression was known to occur. They used those samples to develop a method for grouping patients into low- or high-risk categories based on differences in their DNA.
In the current population-based, prospective study of low-grade oral premalignant lesions, Rosin and colleagues concluded the approach they developed in their 2000 study was able to correctly categorize which patients had lesions that were more likely to progress to cancer.
“The results of our study should help to build awareness that not everyone with a low-grade oral premalignant lesion will progress to cancer,” Rosin said in a press release. “They should also begin to give clinicians a better idea of which patients need closer follow-up.”
The researchers analyzed 296 patients who developed mild or moderate oral dysplasia between 1997 and 2007. Researchers identified patients through BC Oral Biopsy Service, which receives biopsies from dentists and ENT surgeons across British Columbia.
Median follow-up time was 44.6 months.
Patients with high-risk lesions had a 22.6-fold increased risk for progression compared with those who had low-risk lesions (P=.002), the researchers said.
The researchers then added DNA molecular markers called loss of heterozygosity (LOH) — consistently identified as a potential independent risk factor — to the analysis.
Researchers analyzed LOH markers in chromosome regions 3p14.2; 4q26, 4q31.1; 8p21.3; 8p23.3; 9p21; 11q13.3, 11q22.3; 13q12.3-13, 13q14.3; 17p11.2 and 17p13.1.
They used the disease samples from the prospective study and categorized them into low-, intermediate- and high-risk groups.
The 5-year progression rate was 3.1% (95% CI, 0-7.6) among patients in the low-risk group, 16.3% (HR=11.6; 95% CI, 2.7-49.9) among patients in the intermediate-risk group, and 63.1% (HR=52.1; 95% CI, 11.8-230.6) among patients in the high-risk group (P<.001), according to study results.
“That means that two out of every three high-risk cases are progressing,” Rosin said. “Identifying which early lesions are more likely to progress may give clinicians a chance to intervene in high-risk cases and may help to prevent unnecessary treatment in low-risk cases.”
Perspective
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Brian Burkey, MD, FACS
This study finds that certain premalignant lesions of the oral cavity have a higher risk than others of progressing into cancer, and that the risk can be stratified by using molecular techniques and evaluating cellular chromosomal changes. This has great implications. Oral cancer is diagnosed in more than 10,000 people annually and it usually is preceded by premalignant changes, but the majority of premalignant changes do not progress into invasive cancer. Therefore, the problem is how to define a high-risk population that will benefit from early intervention through aggressive screening, surgery or potentially toxic chemoprevention.
The authors show us how to identify low-, intermediate- and high-risk populations based on specific genetic changes in the lesion, and thus allow us to define appropriate populations that might benefit from additional treatments. The difficulty of implementing the study findings is that these chromosomal studies are expensive and not readily available. Also, some may question whether the ultimate outcome of this group of patients with oral premalignant lesions would be improved by screening with this technology. However, this study points us in a direction where we can answer the latter question, and it lets us narrow the group of patients who have a high risk of developing oral cancer so that we can determine if aggressive intervention is in their best interest.
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Zhang L. Cancer Prev Res. 2012;doi:10.1158/1940-6207. CAPR-12-0173.
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