Gene Linked to Poor Prognosis for Melanoma

A gene has been identified that is present in some patients with melanoma, which appears to make the tumor cells more resistant to treatment.

The gene, Tumor protein p63 (TP63), is unexpectedly expressed in a number of melanoma cases and correlates significantly with a worse prognosis and it is hoped this new understanding of what makes some melanoma cells so difficult to kill will help the development of new therapies.

Scientists at Queen Mary, University of London (UK) analyzed 156 melanoma tissue samples from 129 individuals for expression of the protein p63, which is encoded by the gene TP63. Overall, 19 recurrent melanoma samples and 56 metastatic melanoma tumor samples from 49 individuals, 22 males and 27 females, were analyzed. The median age at diagnosis was 60.6 years and the median follow up for this cohort was 1.52 years. The proportion of p63-positive tumors comprised 10/19 (53%) of recurrent tumors and 37/56 (66%) of metastatic tumors.

Overall mortality for recurrent and metastatic tumors was 45% and melanoma-specific mortality was 37%. Median age of death was 62.4 years with median time to death from first recurrence or metastases was 15 months. The number of cases of melanoma is rising faster than almost any other cancer and one of the main risk factors is ultraviolet light, which comes from the sun or sun beds [tanning bed]. While early-stage melanomas can often be removed by surgery, more advanced melanomas are much harder to treat.

Daniele Bergamaschi, PhD, a senior lecturer in cutaneous research at Queen Mary said, "For most patients where the melanoma has spread beyond the skin, there are few effective treatments and overall survival rates for this disease have not changed much over the past 30 years. To develop better treatments we need to understand the basic biology underpinning why these cells are so resistant to being killed."

Dr. Bergamaschi added, "We did not expect to find the TP63 gene expressed in melanoma. It is not usually found in the melanocytes (skin pigment cells), which are the cells from which melanomas develop. However, it appears in some cases this gene is turned on as the tumor forms, and when it does it is linked to a worse prognosis." The study was published on February 18, 2013, in the Journal of Experimental Medicine.

Related Links:
Queen Mary, University of London