Melanoma is increasing in incidence. However, survival outcomes can vary widely even within the same stage and the same histotype. Current American Joint Committee on Cancer¿s (AJCC) staging for cutaneous melanoma is based on primary tumor thickness and presence of ulceration, mitoses, nodal spread, and distant metastases as determinants of prognosis. Given the clinical and biological heterogeneity of primary melanoma, new prognostic tools are needed to more precisely identify the patients most likely to develop advanced disease.
Inflammation plays a central role in melanoma microenvironment changes. In addition, miRNAs are central players in cancer biology and they play a pivotal role in mediating the network communication between tumor cells and their microenvironment. miRNAs also strongly act on some components of the immune system, regulating the activity of key elements such as antigen presenting cells, and can facilitate an immune evasive/suppressive phenotype. Understanding the reciprocal coevolution of melanoma and immune cell phenotypes during disease progression and in response to therapy is a prerequisite to improve current treatment strategies. Such tools would affect clinical surveillance strategies and aid in patient selection for adjuvant therapy.
Here, we propose to study the inflammatory microenvironment and expression of specific microRNAs in primary melanoma and sentinel limph node as prognostic factors to differentiate lesions with high and low malignant potential. To accomplish this task, we sought to analize a group of about 100 primary melanomas and 50 sentinel lymph nodes to correlate specific alterations in inflammatory cytokine/chemokines and miRNAs expression with tumor progression. We will use a combined approach of real time PCR assays to detect both mRNAs and miRNAs as well as in situ immunohistochemistry techniques on paraffin-embedded sections to detect inflammatory cyto-/chemokines.
