Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma

Pedram Gerami, Zuxu Yao, David Polsky, Burkhard Jansen, Klaus Busam, Jonhan Ho, Mary Martini, Laura K Ferris, Pedram Gerami, Zuxu Yao, David Polsky, Burkhard Jansen, Klaus Busam, Jonhan Ho, Mary Martini, Laura K Ferris

Abstract

Background: Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable.

Objective: We sought to provide clinicians with such a tool.

Methods: A 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy. Results were compared with standard histopathologic assessment in lesions with a consensus diagnosis among 3 experienced dermatopathologists.

Results: In 398 validation samples (87 melanomas and 311 nonmelanomas), LINC00518 and/or PRAME detection appropriately differentiated melanoma from nonmelanoma samples with a sensitivity of 91% and a specificity of 69%. We established LINC00518 and PRAME in both adhesive patch melanoma samples and underlying formalin fixed paraffin embedded (FFPE) samples of surgically excised primary melanomas and in melanoma lymph node metastases.

Limitations: This technology cannot be used on mucous membranes, palms of hands, and soles of feet.

Conclusions: This noninvasive 2-gene pigmented lesion assay classifies pigmented lesions into melanoma and nonmelanoma groups and may serve as a tool to help with diagnostic challenges that may be inherently linked to the visual image and pattern recognition approach.

Keywords: LINC00518; biopsy; gene expression; histopathology; melanoma; noninvasive; preferentially expressed antigen in melanoma.

Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Fig 1
Fig 1
Noninvasive adhesive patch skin biopsy.
Fig 2
Fig 2
Receiver operating characteristic curves demonstrating the PLA’s potential to differentiate primary cutaneous melanoma samples from nonmelanoma samples (primarily atypical nevi) based on LINC00518 and/or preferentially expressed antigen in melanoma detection. AUC, Area under the curve.
Fig 3
Fig 3
Comparison of LINC00518 (LINC), actin B (ACTB) and preferentially expressed antigen in melanoma (PRAME) gene expression in patient-derived melanoma xenografts (PDX) compared with nonmelanoma xenografts (A), and in adhesive patch samples of primary cutaneous melanomas processed with the PDX samples as controls (B). Ct, Cycle threshold.

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