Sniffing out cancer: Research on 'scent' of BCC may lead to diagnostic tool

October 1, 2008

The first research on the "scent" of basal cell carcinoma (BCC) holds potential for the development of a rapid, noninvasive diagnostic test for skin cancers and possibly other skin ailments, researchers say.

Key Points

Washington - The first research on the "scent" of basal cell carcinoma (BCC) holds potential for the development of a rapid, noninvasive diagnostic test for skin cancers and possibly other skin ailments, researchers say.

Investigators at the Monell Chemical Senses Center in Philadelphia were intrigued by several recent studies showing that dogs were capable of detecting cancer in human patients.

"We thought it would be really exciting if we could identify what those compounds are," Michelle Gallagher, Ph.D., tells Dermatology Times. "That became our goal: to identify the basic chemicals coming off the skin, and whether they varied with skin cancer."

They identified nearly 100 VOCs, publishing those findings recently in the British Journal of Dermatology.

Then, Dr. Gallagher and colleagues from the University of Pennsylvania's department of dermatology repeated the procedures with 11 patients diagnosed with basal cell carcinoma and 11 matched controls.

Identifying biomarkers

Two VOCs stood out as significantly different between the two groups: Dimethylsulfone increased, while 6-methyl-5-hepten-2-one decreased. Researchers questioned whether these might be biomarkers of BCC.

"We started seeing these differences appear over and over again, and when we compared the cancer patients with the healthy subjects, it really seemed like a viable approach," Dr. Gallagher says.

However, while these biomarkers appear to be associated with BCC, she says, that does not preclude identifying other markers of the disease.

One thing that surprised Dr. Gallagher in the baseline study is that there were no statistically significant differences on the basis of gender. Participants were predominantly Caucasians, and the small sample size was not adequately powered for analysis by race/ethnicity.

"Of course, the larger the sample size, the more differences you can start to see," Dr. Gallagher says.

Researchers observed age differences in levels of VOCs. Dr. Gallagher says she suspects some of these differences may reflect dietary and consumer product usage.

In these cases, certain lipid-soluble fragrance or dietary compounds accrue in body tissue over time. She refers to one study of an "aging odor" in Japanese men that appears to be linked to a diet that is heavy in seafood.

"It is definitely possible" that coinfection with other diseases might affect the expression of VOCs and, perhaps, their use as biomarkers, Dr. Gallagher says.

"We had a patient who was HIV-positive in the basal cell study; his peak for dimethylsulfone was off the chart," she says.

The patient was such an outlier that they decided to exclude his data from analysis so that it would not skew the outcome.

Early detection

The initial BCC study enrolled patients whose tumors already were diagnosed. Now, researchers hope to push back earlier into the disease process.

Dr. Gallagher says, "We want to know, if the skin looks completely healthy, at what stage does the VOC profile change?"

That will be crucial for screening and early diagnosis.

"The earlier you can detect skin cancer, the less invasive it will be to remove it," she says.

If the cancer is diagnosed early enough, it may be possible to treat the condition with topical immunomodulators rather than surgical procedures.

If the diagnostic tool becomes refined enough, perhaps it could be used to monitor response to therapy, or it could be employed in a manner similar to the use of histology in Mohs surgery, which helps to assure that tumor margins are excised with minimal damage to healthy tissue.

Looking at SCC

The Monell researchers want to look at squamous cell carcinoma and melanoma to see if they can identify unique VOC signatures for those cancers as well.

Dr. Gallagher readily acknowledges the importance of "developing the technology into a diagnostic that is appropriate for the clinic," and she is optimistic on that count.

"With the emerging nanosensor 'electronic nose' technology, it seems reasonable that such a device could be programmed to look for these chemical biomarkers at a certain concentration" to create a diagnostic tool that is usable in a doctor's office as part of a regular visit.

"We've all been fascinated by articles in the popular press about dogs sniffing out melanomas, and we've all kind of laughed at it. But maybe there is something to it," says Suephy C. Chen, M.D., assistant professor of dermatology at the Emory University School of Medicine, Atlanta.

She says the retrospective study of 11 patients is interesting, but adequately powered prospective, blinded studies would be needed to satisfy clinicians.

"If it all pans out, I think it would be a very valuable diagnostic, especially because we now have the ability to prescribe imiquimod for basal cell carcinoma," Dr. Chen says.

Performing a biopsy to confirm the diagnosis can leave a scar and defeat the purpose of a noninvasive treatment. A noninvasive tool to confirm the diagnosis would be a useful complement to the topical treatment, Dr. Chen says.

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