Molecular and clinical correlates of HER3 expression in melanoma

Abstract

BACKGROUND: The epidermal growth factor receptor family member HER3 has been implicated in several types of cancer, and recently, drugs targeting HER3 have shown impressive clinical activity. In melanoma, HER3 overexpression has been linked to both metastasis formation and resistance to drug therapy in cell culture models. AIMS: Here, we sought to characterize the expression of HER3 in 187 melanoma biopsies (149 cutaneous, 38 mucosal), as well as in a subset of cutaneous melanoma specimens taken prior to treatment with immune checkpoint blockade therapy (n = 79). METHODS: We analysed the association between HER3 expression via immunohistochemistry, and molecular, clinical, and pathological variables. RESULTS & CONCLUSIONS: Positive HER3 expression (>=1+) was observed in 136 of 187 samples (~73%). HER3 expression was found to be markedly lower in the mucosal melanomas, with 17 of the 38 samples (~45%) given a HER3 score of 0. In cutaneous melanomas, there was a negative association between HER3 expression and mutational load, overall survival after anti-PD-1-based immunotherapy as well as a trend of negative association with PD-L1 expression. Overall, our results indicate that HER3 is a promising therapeutic avenue in cutaneous melanoma worthy of further clinical evaluation.