Noninvasive genomic detection of melanoma

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

Effects of ultraviolet-inactivated herpes simplex virus type I on atopic dermatitis-like lesions in NC/Nga mice: Role of the suppressor of cytokine signaling in the skin

ABSTRACTBackgroundAtopic dermatitis (AD) is characterized by repetitious eczematous skin and is Th2 dominant in nature. Atopic dermatitis lesions have been observed to improve in patients during viral or bacterial infection, such as herpes simplex virus (HSV). A Th 1 pathway established to counter viral infection may possibly be the mechanism for the relief of skin lesions in AD.MethodsIn animal AD models using NC/Nga mice, the effects of local intra- and/or subcutaneous injection of ultraviolet inactivated-HSV were examined for Th1/Th2 regulation through a negative regulation pathway with suppressor of cytokine signaling (SOCS)-3 and 5 using immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction.ResultsLesional skin of HSV-treated mice displayed extensive interleukin (IL)-12p40-positive cellular infiltration compared with non-treated mice and IL-12p40/ signal transducers and activators of transcription (STAT) 4/SOCS5 mRNA expression was noted basically the same in the three groups. Interleukin-4 receptor-positive cellular infiltrates in HSV-treated mice decreased significantly more than in non-treated mice and IL-4 mRNA expression in the three groups was essentially the same, but the expression of STAT6 and SOCS3 mRNA specific for the Th2 regulation pathway was reduced more in HSV-treated compared with non- treated mice. Expression of SOCS3 mRNA in situ in HSV-treated epidermis underwent a far greater reduction compared with expression in non-treated mice.ConclusionsUltraviolet-inactivated HSV treatment would appear to induce a Th1 cellular response and downregulate that of the Th2 pathway in AD-like lesions of NC/Nga mice by bringing about a reduction of SOCS3 expression in the skin. From the present results, certain HSV DNA components may be effective candidates for a new therapeutic approach in refractory AD