They used a 21-gene pattern and were able to properly predict outcomes in nine out of ten patients, according to a paper in Clinical Cancer Research.

A group of researchers have developed a gene-signature test that projects whether a patient will experience a slow or rapid progression from Stage III melanoma to metastatic Stage IV cancer and death.

They used microarrays to measure the expression of more than 30,000 genes in lymph node sections taken from 29 patients with Stage III melanoma. The team found that 2,140 genes were differentially expressed in the sections from people who had a poor outcome (average time to progression, or TTP, of four months) and patients that had a good outcome (average TTP of 40 plus months). Using statistical analyses, they identified 21 genes that could be used to differentiate between the two subtypes of patients.

The resulting gene signature was then used to prospectively analyze a separate group of 10 patients. The test accurately predicted the outcome of 90% of the patients, the investigators report. The one patient who was incorrectly predicted to have a good prognosis actually had a rapid TTP to Stage IV. This patient did go on, however, to have a prolonged survival of six years.

The team also applied the test to previously published data sets and report getting a prediction accuracy of 85%, even though data was not available for all 21 genes that the team identified in their gene signature. Researchers caution that the findings need to be validated by a larger number of patients before the test can be applied routinely as a prognostic tool.

Greater than 70% of patients with Stage III melanoma that has spread to the lymph nodes will rapidly progress to Stage IV melanoma, and die within five years of their diagnosis. However, the remaining patients will have a slow progression to Stage IV and will enjoy prolonged survival.

The inability to distinguish between these patient subtypes means that some patients might undergo aggressive and sometimes toxic treatments unnecessarily. The unpredictable and significant discrepancies in TTP and survival could also cloud the interpretation of results from clinical trials of new melanoma therapies.

The study was done by scientists from the Melbourne Center of the Ludwig Institute for Cancer Research and Pacific Edge Biotchnology. The report appears in the August issue of Clinical Cancer Research.

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