798 Genomic detection of melanoma, W. Wachsman et al. The occurrence of malignant melanoma has been rising for decades, leading to a doubling of the incidence rate over the last 10–20 years.1,2 The invasive form of the disease is already the seventh most common serious cancer in the U.S.A. with a lifetime risk of one in 41 in men and one in 61 in women. Once melanoma has disseminated, the patient’s prognosis is dismal.3–5 Most deaths from melanoma could be prevented, however, if the disease were detected and excised at an early stage, while still conﬁned to the skin.4 For example, in situ melanoma, the earliest skin stage, has a nearly 100% cure rate when adequately excised. Once melanoma has progressed locally, especially if it has invaded to a depth of 4 mm or more, the 10-year survival rate is < 50% because it has already metastasized before the skin lesion was excised. This makes the early detection of melanoma critical to patient survival. Current clinical detection of melanoma relies upon visual cues, including the ‘ABCDE’ criteria for pigmented naevi, and results of optical imaging techniques like dermoscopy and confocal microscopy. Due to the diverse morphologies of pig- mented lesions, early diagnosis of this tumour can be quite challenging.4,6 The occurrence of atypical naevi, precancerous lesions that can mimic the visual presentation of melanoma but do not have the histopathological features of this cancer, is a major confounder to the accurate clinical diagnosis of melanoma. Studies have shown that clinicians are only able to determine whether a suspicious pigmented lesion is melanoma or not with 54–90% sensitivity.6–8 Clinical expertise was found to be a key determinant of melanoma diagnostic accur- acy.8 Using the benign-to-malignant ratio as an endpoint, researchers in Australia found that general practitioners bi- opsied approximately 30 benign pigmented lesions for every melanoma, while dermatologists biopsied more than 12 pigmented lesions for every melanoma they diagnosed.9 Taken together, health care professionals biopsy many pigmented lesions to detect a melanoma, and may also leave some melanomas undetected at their early stages. Techniques to improve the clinical diagnosis of suspicious pigmented skin lesions are based on enhanced imaging meth- ods such as dermoscopy and confocal microscopy. Dermo- scopy has been shown to improve the sensitivity of melanoma detection by 10–27%;10,11 however, some early melanomas are missed by this technique.12 Other detection strategies include sequential digital epiluminescence microscopy, reﬂec- tance confocal microscopy, automated instrumentation for image analysis, MelaFind (Mela Sciences, Irvington, NY, U.S.A.), and the comparison of serial body photographs, e.g. of atypical naevi, taken at frequent intervals.13–17 Reﬂectance confocal microscopy, arguably the more accurate of the confo- cal techniques, does not reach a sensitivity of 100%.18 Although digital epiluminescence microscopy has been shown to improve the sensitivity of melanoma detection signiﬁcantly, in particular for thin lesions, it has a speciﬁcity of < 20%.14 The current gold standard for diagnosing melanoma is histopathological examination of the excised tissue. This necessitates biopsy of the lesion, an invasive, time- and resources-consuming procedure that can be impractical, especially in those patients who have many dysplastic naevi. Moreover, even histopathology has its limitations. Due to its subjective nature, discordant readings between expert dermato- pathologists are reported to occur in 10–35% of potential cases of melanoma.19,20 Epidermal genetic information retrieval (EGIR ; DermTech International, La Jolla, CA, U.S.A.) uses a custom adhesive ﬁlm to sample RNA from stratum corneum noninvasively. RNA recovered from the surface of the skin by EGIR has been quantiﬁed using ribonuclease protection assay, quantitative real-time reverse transcription–polymerase chain reaction (qRT-PCR) and DNA microarray analysis to differentiate irritant from allergic skin reactions and by qRT-PCR to assess changes in gene expression in psoriatic skin lesions in response to biotherapy.21–23 These studies showed the feasibil- ity of using EGIR-harvested RNA to assess differences in dermatopathology. In the current study, we sought to exploit this technology to determine whether the expression proﬁle of RNA in stratum corneum of normal skin differs from that overlying a naevus or a malignant melanoma. We report here that analysis of such EGIR specimens has identiﬁed some 312 genes that differentiate normal skin and naevi from melano- mas, many of which are relevant to the underlying pathology. Furthermore, we have used this EGIR-based strategy to develop a 17-gene classiﬁer that detects both in situ and inva- sive melanoma with high accuracy. Materials and methods Patients and clinical protocols The study protocols were reviewed and approved by the vari- ous Institutional Review Boards. Study subjects gave written informed consent prior to participation and the study was conducted according to the Declaration of Helsinki principles. All study subjects were 18 years or older and had a pigmented lesion 4 mm or greater in diameter that required biopsy due to suspicion for melanoma (Table 1). Study exclusion criteria included application of topical medications to the lesion or use of systemic steroids within 30 days of tape stripping; pres- ence of a generalized skin disorder such as psoriasis, a photo- sensitivity disorder, or eczema; known allergy to tape or latex; use of sunscreen or topical moisturizer within 24 h of tape stripping; and lesions with clinically overt bleeding, ulceration or serous exudation. After informed consent, the suspicious pigmented lesion was taped stripped, as previously described,23 and then biopsied as per standard of care. If a lesion was smaller in size than the 17-mm diameter adhesive tape disc, the outer edge of the lesion was demarcated on the tape with indelible ink. A tape-stripped specimen was used in the study only after the histopathological diagnosis of the biopsied tissue was reviewed at the primary site and conﬁrmed by the central dermatopathology reviewer. As a control, each subject’s normal appearing skin was also sam- pled by tape stripping. Eighty-two per cent of these control specimens were garnered from the mastoid process, with the BJD 2011 The Authors 2011 British Association of Dermatologists 2011 164, pp797–806