Invasive melanoma in vivo can be distinguished from basal cell carcinoma, benign naevi and healthy skin by canine olfaction: a proof-of-principle study of differential volatile organic compound emission

• Published in: British journal of dermatology (1951) Vol. 175; no. 5; pp. 1020 - 1029
• Main Authors: Willis, C.M., Britton, L.E., Swindells, M.A., Jones, E.M., Kemp, A.E., Muirhead, N.L., Gul, A., Matin, R.N., Knutsson, L., Ali, M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2016
• Subjects: Adult; Aged; Animals; Biomarkers, Tumor - analysis; Carcinoma in Situ - diagnosis; Case-Control Studies; Dogs; Double-Blind Method; Female; Humans; Male; Melanoma - diagnosis; Middle Aged; Neoplasm Invasiveness; Nevus, Pigmented - diagnosis; Skin Neoplasms - diagnosis; Smell; Volatile Organic Compounds - analysis
• ISSN: 0007-0963; 1365-2133; 1365-2133
• DOI: 10.1111/bjd.14887

Summary Background Volatile organic compounds (VOCs) are continuously released by the body during normal metabolic processes, but their profiles change in the presence of cancer. Robust evidence that invasive melanoma in vivo emits a characteristic VOC signature is lacking. Objectives To conduct a canine olfactory, proof‐of‐principle study to investigate whether VOCs from invasive melanoma are distinguishable from those of basal cell carcinoma (BCC), benign naevi and healthy skin in vivo. Methods After a 13‐month training period, the dog's ability to discriminate melanoma was evaluated in 20 double‐blind tests, each requiring selection of one melanoma sample from nine controls (three each of BCC, naevi and healthy skin; all samples new to the dog). Results The dog correctly selected the melanoma sample on nine (45%) occasions (95% confidence interval 0·23–0·68) vs. 10% expected by chance alone. A one‐sided exact binomial test gave a P‐value of < 0·01, supporting the hypothesis that samples were not chosen at random but that some degree of VOC signal from the melanoma samples significantly increased the probability of their detection. Use of a discrete‐choice model confirmed melanoma as the most influential of the recorded medical/personal covariates in determining the dog's choice of sample. Accuracy rates based on familiar samples during training were not a reliable indicator of the dog's ability to distinguish melanoma, when confronted with new, unknown samples. Conclusions Invasive melanoma in vivo releases odorous VOCs distinct from those of BCC, benign naevi and healthy skin, adding to the evidence that the volatile metabolome of melanoma contains diagnostically useful biomarkers. What's already known about this topic? Some tumours have been shown to emit characteristic patterns of volatile organic compounds (VOCs). There is anecdotal evidence of canine olfactory detection of melanoma, and some supporting analytical findings, but robust data for a distinct profile of melanoma‐associated VOCs are lacking. What does this study add? We demonstrated by canine olfaction that invasive melanoma in vivo emits a profile of odorous VOCs that differs from those of basal cell carcinoma, benign naevi and healthy skin. The study provides further evidence of the potential for VOCs to be utilized as biomarkers for the objective, noninvasive diagnosis of melanoma. Plain language summary available online