Blood Test Reveals Skin Cancer Spread

New strategies for early diagnosis of metastatic melanoma are urgently needed, as this is an aggressive malignancy with a poor prognosis once metastatic. Although new antimelanoma agents have impressively improved clinical outcomes in patients with advanced melanoma, the disease relapses within months and the prognosis for patients with high volume metastatic melanoma remains very poor.

Scientists at the University of Dundee (Scotland, UK) investigated whether cancer-specific methylation markers identified in patients’ tissues and blood may help reveal the mechanisms underlying melanoma progression, and offer promise as biomarkers for early diagnosis of metastasis and prediction of patient outcome. The study utilized 19 melanoma cell lines, 120 patient tissues, including primary and metastatic melanoma and benign melanocytic naevi and 41 serum samples.

To investigate methylation status of candidate genes, the team employed pyrosequencing, bisulfite sequencing and methylation specific polymerase chain reaction (PCR) and quantitative polymerase chain reaction (qPCR) to evaluate the messenger ribonucleic acid (mRNA) expression. They detected the genes encoding for tissue factor pathway inhibitor 2 (TFPI2), 5'-nucleotidase, ecto (NT5E) and several other candidate genes methylated in melanoma cell lines and in patient materials.

TFPI2 hypermethylation in 11/17 (65%) melanoma cell lines was associated with low mRNA levels and correlated significantly with metastatic disease in tumor samples. Analysis of patients’ sera identified methylated TFPI2 as a promising epigenetic biomarker of metastasis with high sensitivity (85%) and specificity (87%). In contrast, NT5E methylation appears to be a good prognostic biomarker for both primary and metastatic melanoma.

Charlotte M. Proby, BA, MBBS, FRCP, a professor of dermatology and lead author, said, “Using blood tests to assess the landscape of our DNA is a simple way to learn more about what’s going on under the skin. The switching on and off of certain genes seems to affect when, where, and why the melanoma spreads. Our goal is to develop a panel of similar biomarkers that will help us to accurately detect those patients needing extra treatment to fight their melanoma.” The study was presented at the National Cancer Research Institute (NCRI) Cancer Conference held November 4-7 2013 in Liverpool (UK).

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University of Dundee