American researchers led by Iman Osman, M.D., and David Polsky, M.D., Ph.D. measured the amount of a molecule called HDM2 in tissue samples of melanoma from patients who were treated and followed at a university medical center from November 1972 through November 1982. The study found that higher levels of the molecule were associated with a better prognosis; patients with high levels lived significantly longer after surgical treatment than patients with low levels. In addition, the correlation was maintained independently of other prognostic indicators such as tumor thickness.

The difference in outcome between the two patient groups (low and high level of biomarker) was maintained at ten years after treatment. About 53 percent of patients with low levels had suffered a recurrence compared with 28 percent of those with high levels. Overall, 55 percent of those with low levels had died compared with 38 percent with high levels of the molecule.

"We think this is a promising biomarker for melanoma," said Dr. Osman, the lead author. "Previously, we had determined that HDM2 was abundant in melanoma, but we didn't understand what this meant for the patient. With this retrospective study, we were able to assess whether HDM2 levels at the time of diagnosis could help predict the course of the disease," she added. "The strength of our study is the large number of patients and the long-term follow-up that extends up to 18 years in some patients."

"In cancer research there is a great deal of focus on finding these kinds of molecular markers because we need more reliable means of assessing the risk of cancer recurrence," added Dr. Polsky. "Our findings need to be verified independently by other groups before this marker could be used in the clinic."

The researchers tracked levels of HDM2 using an antibody technique that tags the molecule with a colored stain. The molecule is involved in the pathway for the tumor suppressor gene p53. It is not clear at this time why HDM2 levels would be high in people with melanoma, said Dr. Polsky.

Currently, the thickness of a melanoma at the time of diagnosis, sometimes combined with sentinel node biopsy, is used to assess whether a patient's tumor will recur and if additional treatment with immunotherapy is warranted after the cancer is removed. Patients with stage I disease have the thinnest lesions and are therefore the least likely to have a recurrence.

The prognosis usually worsens as the tumor extends deeper into the skin. However, levels of HDM2 in the study did not correlate with tumor thickness. "Tumor thickness is not enough," said Dr. Osman. "Two people with the same tumor thickness under the microscope may require different treatment. This is the reason why better markers can help us refine therapy."

The current study involved 134 patients with stage I, II, or III melanomas. The patients were enrolled in a Melanoma Cooperative Group, which documented important characteristics of each patient's original tumor such as location and thickness. After treatment, the patients were followed for many years.

A new, prospective Melanoma Cooperative Group has been enrolling patients for a study that will track HDM2 and other molecules in tumor material. One of the long-term goals of this program is to integrate the results of molecular analyses of an individual patient's tumor into his or her treatment plan.