Genetic profile information added to traditional staging data improved survival predictions, according to PNAS paper.

Scientists may be able to predict survival rate among melanoma patients by analyzing the activity of genes involved in immune response and gene proliferation, according to researchers at NYU Langone Medical Center. The researchers used DNA-microarray technology to find 266 genes associated with shorter or longer survival among 38 patients whose melanomas had recurred after being surgically removed.  

The study provides some hints about the underlying mechanism of melanoma. “We found that patients who survived longer had gene activity consistent with an immune response,” says Nina Bhardwaj, M.D., Ph.D., professor of medicine, pathology, and dermatology at NYU Langone Medical Center and the study’s senior author.

“Patients who didn’t survive as long didn’t have an up-regulation of those genes but tended to have higher levels of genes associated with cell proliferation, suggesting that if your cells are growing more actively, the tumor is going to grow faster.” The details will appear online this week in the Proceedings of the National Academy of Sciences.  

To help predict survival, doctors routinely assign melanoma to one of four stages, based on tumor size and location. The staging technique can be ambiguous, though. For example, stage III has been subdivided into three groups according to the extent of the tumor growth within the lymph nodes. The latter two subgroups, IIIb and IIIc, correspond to more advanced disease but have proven nearly indistinguishable as indicators of long-term survival.   

When Dr. Bhardwaj’s team added genetic profile information to the traditional staging technique, survival predictions improved substantially. Given that the researchers had found a bevy of cell-growth genes associated with a poorer prognosis, she says, they tested whether they could obtain similar results by staining a tumor specimen to get its mitotic index. The measure of cell proliferation not only helped distinguish between stages IIIb and IIIc but also proved to be the single strongest predictor of patient survival.
The study also found that two other measures of immune response, including the infiltration of tumors by T-cell specialists or by the immune system’s larger collection of white blood cells, also improved predictions when added to the traditional staging system.

“It’s exciting, because we finally have some parameters that might help distinguish between these two stages in terms of survival and possibly address how these patients should be treated,” Dr. Bhardwaj says. She cautions, however, that the study must still be validated with a much larger, independent group of patients.

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