Noninvasive genomic detection of melanoma

Abstract

BackgroundEarly detection and treatment of melanoma is important for optimal clinical outcome, leading to biopsy of pigmented lesions deemed suspicious for the disease. The vast majority of such lesions are benign. Thus, a more objective and accurate means for detection of melanoma is needed to identify lesions for excision.ObjectivesTo provide proof-of-principle that epidermal genetic information retrieval (EGIR™; DermTech International, La Jolla, CA, U.S.A.), a method that noninvasively samples cells from stratum corneum by means of adhesive tape stripping, can be used to discern melanomas from naevi.MethodsSkin overlying pigmented lesions clinically suspicious for melanoma was harvested using EGIR. RNA isolated from the tapes was amplified and gene expression profiled. All lesions were removed for histopathological evaluation.ResultsSupervised analysis of the microarray data identified 312 genes differentially expressed between melanomas, naevi and normal skin specimens (P<0·001, false discovery rate q<0·05). Surprisingly, many of these genes are known to have a role in melanocyte development and physiology, melanoma, cancer, and cell growth control. Subsequent class prediction modelling of a training dataset, consisting of 37 melanomas and 37 naevi, discovered a 17-gene classifier that discriminates these skin lesions. Upon testing with an independent dataset, this classifier discerned in situ and invasive melanomas from naevi with 100% sensitivity and 88% specificity, with an area under the curve for the receiver operating characteristic of 0·955.ConclusionsThese results demonstrate that EGIR-harvested specimens can be used to detect melanoma accurately by means of a 17-gene genomic biomarker.

Strategien zur nichtinvasiven Diagnostik des Melanoms

“…Die EGIR™-Technologie basiert auf der Tatsache, dass Melanome ein abweichendes Genexpressionsprofil aufweisen, was zu einer veränderten RNA-Transkription führt. Mithilfe eines 17-Gen-Biomarkers konnten in früheren Studien In-situ-und invasive Melanome mit einer Sensitivität von 100 % und einer Spezifität von 88 % erkannt werden [48,49]. Die Probengewinnung bei diesem Verfahren mithilfe eines Klebestreifens ist einfach und zeiteffektiv.…”

Screening and Non-Invasive Evaluative Devices for Melanoma Detection A Comparison of Commercially Available Devices and Dermoscopic Evaluation

“…The commercialized version of this technique has been developed by DermTech (LaJolla, CA) and is called the Epidermal Genetic Information Retrieval (EGIR) system. Using EGIR and a 17-gene classification signature, researchers were able to identify melanomas in a 128 lesion test set with 100% sensitivity and 88% specificity [57]. EGIR analysis of control samples taken from normal skin (n=79), solar lentigenies (n=22) and basal cell carcinoma (n=18) was able to identify all but one BCC lesion as non-melanoma.…”

Molecular testing to differentiate melanoma from benign nevi: The gold standard limitation

“…This methodology is the central paradigm of many studies using fluorescent in situ hybridization (FISH) 2 and genetic expression studies using polymerase chain reaction (PCR) techniques. [3][4][5] There are several limitations with this method of validation. Any test that is both structured and validated using a gold standard test can only be expected to be as accurate as the gold standard test itself in a best case scenario (given that the test is designed to maximize concordance with the gold standard test).…”