The number and localization of CD68+and CD163+macrophages in different stages of cutaneous melanoma

The role of tumor-associated macrophages (TAMs) in cutaneous melanoma is controversial. TAMs include immunogenic and immunosuppressive subtypes, and have distinct functions according to their microanatomical localization. Our aim was to investigate TAMs in benign, premalignant, and malignant melanocytic lesions to determine possible associations with tumor progression and clinicopathological characteristics. In total, 184 tissue samples, including benign and dysplastic nevi, in-situ melanomas, superficial (Breslow's depth < 1 mm), and deep (Breslow's depth > 4 mm) invasive melanomas and lymph node metastases, were analyzed for macrophage content. Samples were stained immunohistochemically for CD68 and CD163, representing all TAMs and M2-macrophages, respectively. Macrophages were counted by hotspot analysis, and assessed semiquantitatively from the tumor cell nests and stromal component of malignant cases. CD68+ and CD163+ TAMs were more abundant in invasive melanomas compared with benign nevi. The proportion of TAMs in the tumor nests was higher in deep melanomas and lymph node metastases compared with superficially invasive melanomas. High amounts of CD68+ macrophages in tumor cell nests were associated with recurrence, whereas low CD163+ macrophage proportion in tumor stroma was associated with recurrence and in primary melanomas also with poor overall survival. TAMs seem to promote tumor progression in cutaneous melanoma. In particular, CD68+ TAMs and their abundance in tumor nests were associated with poor prognostic factors. However, the correlation of low stromal CD163+ TAM proportion with a poor prognosis indicates that the role of TAMs depends on their subtype and microanatomical localization.