A Johns Hopkins scientist and a team of collaborators have discovered how precancerous moles may progress to melanomas, the most deadly type of skin cancer. The preliminary report, in the Aug. 15 issue of Cancer Research, describes a link between two genes that trigger skin cancers and could serve as early diagnostic markers for the disease.

The researchers say that in melanomas a cell growth regulatory gene known as Id1 deactivates an important tumor suppressor gene, p16/Ink4a, allowing cancer cells to grow uncontrollably. High levels of Id1 proteins are found only in the first stages of melanoma, allowing it to be detected and treated while still in a curable stage.

"Telling the difference between precancerous moles and early-stage melanoma can be very difficult, and the treatments for these two lesions differ significantly," explains Rhoda Alani, assistant professor of oncology, dermatology, molecular biology and genetics and director of the study. "If it's melanoma, you want to catch it very early and treat it aggressively by removing as much tissue as possible to cure the disease." Since Id1 is expressed in early-stage melanoma, it has the potential to serve as a definitive diagnostic marker although more studies are needed to confirm this use.

The scientists studied Id1 protein expression in 21 tissue samples from a variety of skin cancers, including normal noncancerous moles (benign nevus), precancerous moles (dysplastic nevus), early-stage melanoma (in-situ melanoma), invasive melanoma and metastatic melanoma. "We found high levels of Id1 activity in the earliest phases of melanoma, when it's limited to the top layer of the skin (or epidermis). Precancerous moles, invasive and metastatic melanomas do not express high levels of Id1," reports Alani. Larger studies are planned.

The scientists speculate that while the Id1 gene shuts off p16/Ink4a in early melanomas and lifts the brake on uncontrolled cancer cell growth, various mutations or other DNA changes must also occur to the p16/Ink4a gene to damage it beyond repair. So, as the cancer progresses, Id1 becomes less important for shutting off the gene. "This may explain why we see lower expression of Id1 in more advanced melanomas," Alani says.

Melanoma can progress very rapidly and spread to other parts of the body. When treated early, the chance for cure is very high. Only 12 percent of people with metastatic melanoma survive beyond five years.

Melanoma will strike 51,400 people in the United States this year, and 7,800 will die from the disease.

In addition to Alani, participants in this research are David Polsky from NYU Medical Center and Alison Zuyung Young and Klaus J. Busam from Memorial Sloan-Kettering Cancer Center. This research was funded by The National Institute of Arthritis, Musculoskeletal and Skin Diseases.

Related Web Site
Johns Hopkins Melanoma and Cutaneous Oncology Group