PHILADELPHIA--A team of Canadian scientists may have discovered a wayto use a simple dye as a litmus test to identify abnormal areas of themouth that may become cancers.
According to a study published in the September 1 issue of "CancerResearch", the scientists found that lesions that took up the dye knownas toluidine blue were six times more likely to become oral cancers.
The team also discovered that the dye-staining lesionscontained molecular alterations that are linked to high risk of oralcancers -- even at early stages.
"In oral cavity lesions, tissue that stained positive withtoluidine blue were more likely to advance to cancer than lesions thatdid not stain with the dye," said Miriam Rosin, Ph.D., Director of theBC Cancer Agency's British Columbia Oral Cancer Prevention Program andProfessor, Simon Fraser University. Rosin is the senior author on thestudy, funded by the National Institute of Dental and CraniofacialResearch, of the National Institutes of Health.
Toluidine blue is an accepted indicator of oral cancers, Rosinsaid. The current studies, however, demonstrate that the dye accuratelypredicts which pre-malignant lesions are likely to advance towarddisease. Those lesions appear as white or, less frequently, redpatches.
"The vast majority of those white patches are often from minorinflammation and irritation," Rosin said. Some, however, are inclinedto become cancer--and are the ones targeted by this simple imagingtechnology.
In the study of 100 patients, Rosin and her colleagues learnedthat toluidine blue-stained lesions became squamous cell carcinomasmore quickly than lesions that did not stain. The scientists alsodetermined that dye-stained oral lesions were more likely to beaberrant not only at the gross tissue level but at the moleculargenetic level as well. Toluidine blue was applied to lesions in themouths of patients during dental visits to determine the value of thestain for imaging precancerous lesions.
"Oral premalignant lesions that stained with toluidine blueconsistently contained loss of chromosomal genetic information," Rosinsaid. In patients with dye-stained lesions, Rosin and colleagues founda strong association with loss of genetic information, termed loss ofheterozygosity (LOH), on one or more chromosomes.
"Patients with positively stained tissue had a higherincidence of LOH at multiple sites, including regions on chromosomearms 3p or 9p or both as well as on parts of other chromosomes" Rosinsaid. Rosin's Cancer Research article reports results from the initialphase of a long term study that followed 100 patients for 44 months. Bythe completion of the longitudinal study, Rosin and colleagues willmonitor 400 patients.
The current report links the staining of cells with toluidineblue in mouth tissue to the higher risk of patients likely to developsquamous cell carcinomas. When biopsied, lesions that stained blue mostoften showed microscopic abnormal tissue development � dysplasia � thatis associated with cancer risk.
The Rosin team then established that the dye-stained lesionshad characteristic molecular alterations that are linked to higher riskfor oral cancers -- even when the dye stained tissue is at an earlystage, when dysplasia is minimal. Cells with molecular changes took upthe blue dye before the lesion acquired extensive dysplasia. Thefindings are among the first steps in designing and implementing animaging screening program that dentists and oral hygiene professionalscan use to make first-line decisions about early stage biopsies andreferrals for anti-cancer related care.
More than 300,000 people worldwide will be diagnosed with oralcancer this year. In the United States, 30,000 people will develop oralcancers. The five-year survival rate for oral cancer remains between 40and 50 percent--a statistic that hasn't changed over the past severaldecades.
"The disease is usually identified fairly late inprogression," Rosin said. "At that stage, it is frequently not amenableto the successful intervention that we'd like. The whole deal ofchanging survival outcome is that you have to get at the diseaseearlier."
British Columbia is a likely setting for developing a triagemodel to screen and identify high risk lesions among dental patients.Ninety percent of the Province's residents see a dentist at least onceevery two years. Approximately 2,500 dentists in British Columbia forma potential Province-wide screening network that will forward high riskpatients to special care facilities.
"With enough training of those who are doing the screening,the dye should help the clinicians find those patients with lesionsthat should really be moved forward for assessment," Rosin said.Training and technology should enable the people at the point ofscreening to determine whether the lesion should be monitored, or ifthe patient should be referred for further assessment. In some cases,the dentist can decide immediately whether a biopsy should be taken atthat point.
The multidisciplinary research team that collaborates withRosin includes pathologists, oral medicine specialists, dentists, oralsurgeons, radiation oncologists, molecular biologists, statisticiansand epidemiologists.
Her colleagues include, the lead author on the publication,Lewei Zhang, Catherine Poh, Robert Priddy, University of BritishColumbia; Michele Williams, Joel Epstein, Scott Durham, Nhu Le, GregHislop, John Hay, Wan Lam, British Columbia Cancer Agency/CancerResearch Center; Hisae Nakamura, Denise Laronde, Simon FraserUniversity; and Ken Berean, Vancouver Hospital and Health SciencesCenter, Vancouver, B.C., Canada.
Founded in 1907, the American Association for Cancer Research is aprofessional society of more than 24,000 laboratory, translational, andclinical scientists engaged in all areas of cancer research in theUnited States and in more than 60 other countries. AACR's mission is toaccelerate the prevention and cure of cancer through research,education, communication, and advocacy. Its principal activitiesinclude the publication of five major peer-reviewed scientificjournals: "Cancer Research"; "Clinical Cancer Research"; "MolecularCancer Therapeutics"; "Molecular Cancer Research"; and "CancerEpidemiology, Biomarkers & Prevention". AACR's Annual Meetingsattract nearly 16,000 participants who share new and significantdiscoveries in the cancer field. Specialty meetings, held throughoutthe year, focus on the latest developments in all areas of cancerresearch.
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