The myPath® Melanoma test is intended as an adjunctive diagnostic tool for melanocytic lesions that are difficult to classify by histopathology alone.

Using qRT-PCR technology, the test objectively distinguishes melanoma from benign nevi with greater than 90% accuracy.

In the initial discovery phase of test development, 79 candidate genes were selected based upon published data demonstrating their differential expression in melanoma compared with benign nevi or their increased expression in aggressive tumors.9-17

This panel was refined to a set of the 40 genes that most effectively differentiated benign and malignant melanocytic lesions, and these genes were then further assessed in a training cohort of archival formalin-fixed paraffin-embedded melanocytic lesions (n = 464).

Gene Components

myPath Gene Components

Housekeeping genes included: CLTC, MRFAPI, PPP2CA, PSMA1, RPL13A, RPL8, RPS29, SLC25A3, and TXNLI

numerical-score

Statistical modeling identified a subset of 14 genes grouped into three distinct gene components which provided the greatest sensitivity and specificity. These 14 signature genes are involved in cell differentiation and cellular immune signaling.

Expression of the signature genes is normalized to that of 9 housekeeper genes prior to the application of a weighted algorithm that combines the measurements of all signature genes and generates a single numerical score.

Distribution of myPath Scores

Sensitivity

Specificity

The association of this score to the histopathologic diagnosis of the melanocytic lesion was assessed in an independent clinical validation cohort (N = 437) and revealed a sensitivity of 90% and specificity of 91% in differentiating benign from malignant melanocytic lesions.

The accuracy with which myPath Melanoma distinguishes melanoma from nevi has been assessed using a histopathologic standard in which at least two dermatopathologists were required to be in agreement regarding diagnosis.

Initial diagnosis by a dermatopathologist at time of clinical presentation

Finalized pathology report submitted with archived lesional tissue

If discordance between initial and second diagnosis, adjudicative review by a third dermatopathologist

Second diagnosis made by an expert dermatopathologist blinded to initial dianosis

Diagnosis assigned to lesions based on concordance by 2 dermatopathologists

Assess correlation between diagnosis and myPath Melanoma result

myPath Melanoma was developed to be clinically applicable across a broad range of melanocytic lesions, including superficial spreading melanoma, lentigo maligna, lentigo maligna melanoma, dysplastic nevi, and Spitz tumors.

Ongoing studies continue to further assess the performance of myPath Melanoma within these various subtypes of melanocytic lesions.

melanoma-table
nevi-table

myPath Melanoma Gene Component Information

The first component is two measurements of the gene PRAME, which stands for preferentially expressed antigen in melanoma.18

PRAME encodes a cancer-testis protein19 that is aberrantly expressed in melanoma. It appears to contribute to tumorigenesis by functioning as a dominant repressor of retinoic acid receptor signaling20 and / or down-regulation of TRAIL expression.21

The second component contains five genes from the S100A family: S100A7, S100A8, S100A9, S100A12, and PI3. The products of these genes are involved in multiple cellular processes. S100A9 is a calcium binding protein often found in combination with S100A8 as part of an immunogenic protein heterodimer.22 Increased S100A8 and S100A9 levels are detected in many malignant neoplasms,23-25 both within tumor cells and within infiltrating immune cells.

The third component contains 8 genes involved in tumor immune response signaling: CCL5, CD38, CXCL10, CXCL9, IRF1, LCP2, PTPRC, and SELL. Many of these genes produce chemokines or chemokine receptors that regulate leukocyte trafficking. Chemokines can suppress or promote the growth of a neoplasm by acting on cells of the tumor microenvironment, including leukocytes, endothelial cells, and fibroblasts, but they may also affect tumor cells themselves by regulating migration, invasion, proliferation, and resistance to chemotherapy.26

The fourth component is a group of nine housekeeping genes whose measurement allows normalization of the RNA expression for analysis.

Complete results from the clinical validation of myPath Melanoma were published in the
April 2015 issue of the Journal of Cutaneous Pathology.