title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Amersham Hospital, Buckinghamshire Healthcare NHS Trust, Amersham, HP7 0JD, U.K. carolyn.willis@buckshealthcare.nhs.uk.
authors.forename: C M
authors.initials: CM
authors.lastname: Willis
authors.affiliation: Department of Dermatology, Amersham Hospital, Buckinghamshire Healthcare NHS Trust, Amersham, HP7 0JD, U.K.
authors.forename: L E
authors.initials: LE
authors.lastname: Britton
authors.affiliation: Search Dogs UK, 9 Church Road, Thornton-Cleveleys, Lancashire, FY5 2TX, U.K.
authors.forename: M A
authors.initials: MA
authors.lastname: Swindells
authors.affiliation: Department of Statistical Science, University College London, Gower Street, London, WC1E 6BT, U.K.
authors.forename: E M
authors.initials: EM
authors.lastname: Jones
authors.affiliation: Department of Dermatology, Amersham Hospital, Buckinghamshire Healthcare NHS Trust, Amersham, HP7 0JD, U.K.
authors.forename: A E
authors.initials: AE
authors.lastname: Kemp
authors.affiliation: Department of Dermatology, Amersham Hospital, Buckinghamshire Healthcare NHS Trust, Amersham, HP7 0JD, U.K.
authors.forename: N L
authors.initials: NL
authors.lastname: Muirhead
authors.affiliation: Department of Dermatology, Amersham Hospital, Buckinghamshire Healthcare NHS Trust, Amersham, HP7 0JD, U.K.
authors.forename: A
authors.initials: A
authors.lastname: Gul
authors.affiliation: Department of Dermatology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, U.K.
authors.forename: R N
authors.initials: RN
authors.lastname: Matin
authors.affiliation: Faculty of Medicine and Health Sciences, Linköping University, 581 83, Linköping, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Knutsson
authors.affiliation: Department of Dermatology, Amersham Hospital, Buckinghamshire Healthcare NHS Trust, Amersham, HP7 0JD, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Ali
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002278:Carcinoma in Situ / Q000175:diagnosis*; D016022:Case-Control Studies; D004285:Dogs; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009508:Nevus, Pigmented / Q000175:diagnosis*; D012878:Skin Neoplasms / Q000175:diagnosis*; D012903:Smell; D055549:Volatile Organic Compounds / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D055549:Volatile Organic Compounds