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BRAF Protein Expression Potential New Marker for Mortality Risk in Melanoma

September 2014, Vol 5, No 7

Toronto, Ontario—BRAF protein expression is correlated with melanoma progression and poor patient survival, according to recent studies that were reviewed at the 2014 Canadian Dermatology Association annual conference. The team of researchers was given the best scientific poster presentation award at the meeting.

The first meta-analysis (Safaee Ardekani G, et al. PLoS One. 2012;7:e47054) demonstrated a 1.7 hazard ratio (HR) for mortality from melanoma among patients with a BRAF V600E mutation. A subsequent study indicated that high BRAF protein expression is also a significant prognostic factor in patients with primary melanoma (Safaee Ardekani G, et al. Br J Dermatol. 2013;169:320-328).

“We found that high BRAF protein expression is associated with poor prognosis and lower patient survival over 5 years of follow up,” Gholamreza Safaee Ardekani, MD, a PhD candidate, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, told Value-Based Cancer Care. “This means BRAF protein expression could be a cheap and feasible prognostic factor to predict an elevated risk of death in melanoma patients.”

Based on the 4 melanoma studies that involved 674 patients, the 2012 meta-analysis revealed a 47.8% prevalence rate of BRAF mutation in melanoma samples and a 9.6% prevalence rate in colorectal cancer samples. It also showed a 1.7 HR for mortality in patients with the BRAF V600E mutation compared with those without the BRAF mutation.

The team then explored the correlation between BRAF protein expression and melanoma progression, which had not been examined before. The investigators evaluated BRAF protein expression in tissue samples of patients with melanoma in the Vancouver General Hospital’s tissue bank from 232 patients with primary melanoma and in 138 patients with metastatic melanoma.

In the 2013 study, the researchers found a significant correlation between high BRAF protein expression and other key prognostic markers, including thicker tumors, a greater likelihood of ulceration, and higher stage of disease. Furthermore, high BRAF protein expression in primary melanoma was associated with a 2.08 HR for worse overall survival and a 2.39 HR for worse disease-specific survival.

However, BRAF expression was not correlated with survival in patients with metastatic melanoma. A multivariate Cox regression analysis showed that stage and tumor thickness, but not BRAF expression, were independent prognostic factors for poor overall and disease-specific survival among patients with either form of melanoma. There was also an association between high BRAF protein expression and the presence of the BRAF V600E genetic mutation, but this was not statistically significant.

The researchers concluded that BRAF protein expression can be an inexpensive prognostic marker for disease progression and poor survival in melanoma.

“This is a very exciting area of research, but the exact molecular mechanism behind these observations needs to be further investigated,” Dr Safaee Ardekani told Value-Based Cancer Care.

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