Canine melanomas: MiTF and p38 expression and its correlation with the presence of lymphocytic infiltrate, proliferation, and survival

The microphthalmia-associated transcription factor (MiTF) is considered a promoter of carcinogenesis in melanocytes and regulates several cellular processes. Its suppression in cell cultures is a consequence of the action of pro-inflammatory cytokines, and in rats, its downregulation occurs via the p38 pathway. This study aimed to evaluate the expression of MiTF and p38 in canine melanomas using immunohistochemical assays and to verify the correlations between this expression and the presence of an inflammatory infiltrate, tumor size, mitotic index, and animal survival. One hundred seventeen samples of canine melanomas from the oral cavity/digits (n = 74) and skin (n = 43) were analyzed. In oral/digit melanomas, positive relationships were observed between larger tumors (p = 0.007), higher mitotic index, and the absence of MiTF expression. In cutaneous melanomas, MiTF expression was correlated with a greater number of tumors, whereas p38 expression was associated with smaller tumors, the presence of a lymphocytic infiltrate, and prolonged survival. We infer that the expression of MiTF and p38 is higher in canine skin tumors and that this expression may be related to reduced aggressiveness of these neoplasias and less tumor progression. Interestingly, the reduced MiTF expression observed in larger and more mitotically active tumors, such as oral/digit melanomas, appears to contrast with its known role in promoting carcinogenesis. However, this reduction may reflect dedifferentiation and increased aggressiveness of neoplastic melanocytes.