IL-10 expression by primary tumor cells correlates with melanoma progression from radial to vertical growth phase and development of metastatic competence

• DOI: 10.1038/modpathol.2011.5
• Publication Date: 2011-02-11T15:18:35Z
• Authors: Eijun Itakura; Rong-Rong Huang; Duan-Ren Wen; Eberhard Paul; Peter H Wünsch; Alistair J Cochran
• Keywords: 0301 basic medicine; Nevus, Pigmented; Skin Neoplasms; Article; Interleukin-10; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; 0302 clinical medicine; Biomarkers, Tumor; Disease Progression; Humans; Neoplasm Invasiveness; RNA, Messenger; Melanoma

Downregulation of the immune system facilitates tumor progression at different stages of cutaneous melanoma. Sentinel nodes, the first lymph nodes on lymphatics draining directly from a primary melanoma, are immune downregulated by tumor-generated immunosuppressive cytokines, including interleukin-10 (IL-10). To better understand the kinetics of sentinel node suppression, we investigated IL-10 expression by melanoma cells and tumor-associated macrophages and lymphocytes at different stages of primary melanoma evolution. We used reverse-transcriptase in situ PCR to identify the cellular sources of IL-10 mRNA in 39 melanomas. IL-10 mRNA was identified in tumor cells of 2 of 6 melanomas in situ (33%), of 17 of 21 invasive melanomas (81%) and of 11 of 12 metastatic melanomas (92%). Higher IL-10 expression correlates with tumor progression, with differences between melanoma in situ, invasive melanoma and metastatic melanoma. In primary melanomas, the IL-10 mRNA content of tumor cells correlates with Clark's level. There was significantly more IL-10 mRNA in vertical growth-phase melanoma cells than in radial growth-phase cells. In a logistic regression model, moderate-to-high IL-10 mRNA expression by tumor cells was significantly associated with vertical growth-phase melanoma. IL-10 mRNA was detected in melanoma-associated macrophages and lymphocytes. In invasive melanomas, IL-10 mRNA reactivity of macrophages decreased as Clark's level increased. Alterations of immunity by IL-10 derived from melanoma cells and melanoma-associated macrophages and lymphocytes potentially facilitate evolution of the primary melanoma and render regional lymph nodes susceptible to metastases.