
The present study aimed to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)‐β signaling to the loss of AMBRA1 in the epidermis overlying the primary tumor and disruption of epidermal integrity. Immunohistochemistry was used to analyze AMBRA1 and TGF‐β2 in a cohort of 109 AJCC all‐stage melanomas, and TGF‐β2 and claudin‐1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. This study showed loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin‐1 expression (P < 0·05), parakeratosis (P < 0·01), and cleft formation in the dermoepidermal junction (P < 0·05). Collectively, these data suggest a paracrine mechanism whereby TGF‐β2 causes loss of AMBRA1 overlying high‐risk AJCC early‐stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumor ulceration.
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