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

ABSTRACT: Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable.We sought to provide clinicians with such a tool.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.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.This technology cannot be used on mucous membranes, palms of hands, and soles of feet.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.

SUBMITTER: Gerami P

PROVIDER: S-EPMC5599145 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Gerami Pedram P Yao Zuxu Z Polsky David D Jansen Burkhard B Busam Klaus K Ho Jonhan J Martini Mary M Ferris Laura K LK

Journal of the American Academy of Dermatology 20161001 1

<h4>Background</h4>Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable.<h4>Objective</h4>We sought to provide clinicians with such a tool.<h4>Methods</h4>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 sa ...[more]

PMID: 27707590

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Project description:ImportanceBreslow thickness is a 1-dimensional surrogate prognostic feature for tumor size, yet tissue sections have 2 dimensions. Therefore, a 2-dimensional feature, calculated tumor area (CTA), was devised.ObjectiveTo determine CTA precision and prognostic value.Design, setting, and participantsThis retrospective cohort of patients with cutaneous melanoma presented to the Leicester and Nottingham National Health Service hospital trusts in the United Kingdom. Eligible patients in the Leicester development sample had available primary tumor tissue; a diagnosis from January 1, 2004, through December 31, 2011; invasive disease; and Leicestershire residency. Patients in the Nottingham validation sample had an anonymized spreadsheet with primary melanoma diagnosed from January 1, 2003, through December 31, 2005, or from January 1, 2008, through December 31, 2010. From a starting population of 1463 patients in both data sets, a total of 224 (15.3%) were excluded to yield a study population of 1239. Data were analyzed from April 30, 2018, through January 10, 2019.InterventionAn observational analysis of the prognostic value of CTA in patients with cutaneous melanoma.Main outcomes and measuresIndependent association of CTA with melanoma-specific survival and confounding effect of CTA on Breslow thickness in survival analysis.ResultsA total of 1239 patients with melanoma were assessed, including 649 (52.4%) women, with a median age of 60 years (interquartile range, 47-71 years). An intraclass correlation coefficient for CTA on 13 cases was 0.99. In 918 patients in the Leicester cohort, CTA was an independent prognostic factor in Cox proportional hazards regression models after adjusting for Breslow thickness, age, sex, ulcer, mitotic rate, and microsatellites (hazard ratio [HR], 1.87; 95% CI, 1.49-2.34; P < .001). Validation in 321 patients in the Nottingham cohort showed an HR of 1.55 (95% CI, 1.15-2.09; P = .005) and in the combined 1239 cases, an HR of 1.70 (95% CI, 1.43-2.03; P < .001). Breslow thickness was significant in multivariable analysis only when CTA was not in the model. The relative importance of CTA was shown by its retention in all 100 bootstrap multivariable models with backward selection, whereas Breslow thickness was retained in only 53. Melanomas stratified by CTA showed wider separation of survival curves than those stratified by Breslow thickness using the American Joint Committee on Cancer Staging Manual, 8th Edition (HRs, 1.00 to 41.46 vs 1.00 to 36.95, respectively), and the model with CTA categories had a Bayesian information criterion difference of 13.9 compared with T category, indicating substantially better fit. This model had a Harrell C index of 83.7%, and bootstrap analysis showed little evidence of model optimism, with a corrected calibration slope of 0.99.Conclusions and relevanceThis study provides a novel microscopic feature, CTA, with evidence of its independent prognostic value. This evidence suggests that CTA should be a priority for further study.

Dataset Information

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

Publications

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

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