BRAF and melanoma: Intriguingly, when compared to BRAF V600E-negative patients, heterogeneous BRAF V600E acral melanoma patients had worse MSS (Figure 4C) with a significant difference and a small p value (p = 0.0065), suggesting that heterogeneous acral melanomas, even though they contain BRAF-negative cells in various proportions, are different from BRAF-negative acral melanomas in the tumor biology and are able to act in an aggressive manner.