Table 3 A 17-gene melanoma classiﬁer accurately discriminates melanoma from naevi Histopathological diagnosis Melanoma Naevus 37 2 Training set Test set Melanoma Naevus Melanoma Naevus 0 35 39 11 0 78 This level of accuracy made us question the original pathol- ogy readings on the naevi deemed to be melanomas, or falsely positive, by the 17-gene classiﬁer. Therefore, each of the 13 false-positive specimens was serially sectioned and re-reviewed by both primary and central dermatopathologists. In so doing, it was determined by both pathologists that one of 13 false- positive naevi actually harboured an invasive superﬁcial spreading melanoma (the specimen denoted by an arrow in Fig. 3) (photomicrographs are provided in Fig. S1; see Sup- porting Information). Biological functions of the 17-gene classiﬁer Among the 17-gene classiﬁer (Table 4), nine genes (ACTN4, CMIP, CNN2, TTC3, VDAC1, NAMPT, RPL21, RPS15 and RPL18) are located in the cytoplasm, ﬁve genes (EDNRB, GPM6B, TMEM80, KIT and TRIB2) are in the plasma mem- brane, PRAME is in the nucleus and two genes (BC020163 and MGC40222) are unknown. KIT, a receptor tyrosine kinase, and EDNRB, a G-protein coupled receptor, are critical regulators in melanocyte development and pigmentation sig- nalling, hair and skin development, and melanoma progres- sion (Fig. 2). The gene encoding preferentially expressed antigen in melanoma (PRAME) is not only involved in mela- Table 4 List of the 17-gene melanoma classiﬁer 2011 The Authors BJD 2011 British Association of Dermatologists 2011 164, pp797–806 Genomic detection of melanoma, W. Wachsman et al. 803 noma progression but is also implicated in ovarian cancer, neoplasia and breast cancer.29,30 The biological functions of genes in the 17-gene classiﬁer analysed by IPA were primarily involved in cell death (ACTN4, CNN2, EDNRB, KIT, NAMPT, PRAME, TRIB2 and VDAC1), cellular development (EDNRB, KIT, PRAME, TRIB2, TTC3, CNN2, ACTN4, VDAC1 and NAMPT), hair and skin development (EDNRB and KIT), cancer (EDNRB, KIT, TTC3, NAMPT, PRAME and RPS15) and neurological disease (EDNRB, KIT, NAMPT, RPL21 and TTC3). In addition, EDNRB and KIT were used as clinical drug targets for treatment of metastatic melanoma and so was NAMPT in gastric cancer.31–33 These results demonstrate that most of the genes in this classi- ﬁer, which distinguishes melanoma from naevi, are involved in melanoma and cancer. Discussion In this study we have demonstrated that EGIR, noninvasive tape stripping of stratum corneum, can be used to detect mel- anoma. We have identiﬁed 312 genes that are differentially expressed between melanoma, naevi and normal skin. This is the ﬁrst demonstration that EGIR, a method that samples material from stratum corneum, is capable of detecting signals from cells that typically exist in the basal layer of the epidermis. In addition, EGIR technology was also able to discriminate melanomas from naevi, including dysplastic naevi, with high sensitivity and speciﬁcity using 422 differentially expressed genes. Reducing the number of genes to 17, a more practical number that could be tested clinically, still resulted in a classi- ﬁer with 100% sensitivity and 88% speciﬁcity for the detection of in situ and invasive superﬁcial spreading melanoma, lentigo maligna and lentigo maligna melanoma with an ROC AUC of better than 0Æ95. This 17-gene classiﬁer also discriminates Gene name ACTN4 BC020163 CMIP CNN2 EDNRB GPM6B KIT MGC40222 NAMPT PRAME RPL18 RPL21 RPS15 TMEM80 TRIB2 TTC3 VDAC1 GenBank U48734 AW342078 AI819630 NM_004368 M74921 AW148844 NM_000222 N44676 NM_005746 NM_006115 AV738806 AL356414 NM_001018 AI739035 NM_021643 NM_003316 AL515918 Description Actinin, alpha 4 Homo sapiens, clone IMAGE:4346533, mRNA c-Maf-inducing protein Calponin 2 Endothelin receptor type B Glycoprotein M6B v-kit Hardy–Zuckerman 4 feline sarcoma viral oncogene homolog Hypothetical protein MGC40222 Nicotimamide phosphoribosyltransferase Preferentially expressed antigen in melanoma Ribosomal protein L18 Ribosomal protein L21 Ribosomal protein S15 Transmembrane protein 80 Tribbles homolog 2 (Drosophila) Tetratricopeptide repeat domain 3 Voltage-dependent anion channel 1