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Cutaneous melanoma is the most aggressive type of skin cancer, with high invasive potential. Lentigo maligna melanoma (LMM) is a relatively rare type, accounting for about 10% of all melanomas, while the most common subtype of melanoma on the face, typically on chronically sun-exposed skin of elderly people. Its in situ stage is lentigo maligna (LM). During the process of transformation from LM to LMM, tumor cells secrete or induce the release from neighboring cells of large amounts of matrix metalloproteinases (MMPs) that degrade the extracellular matrix. Some MMPs, as MMP3 and MMP9 expressed melanoma cells is associated with statistical significance in both in vitro and in vivo studies, with an invasive phenotype. Unfortunately, there is scarce data published about MMPs expression in LM∕LMM, as majority of research on melanoma refer to superficial spreading and nodular melanoma. Our personal, unpublished yet fully data is an attempt to complete a specific panel of immunohistochemical markers that could explain the slow growing rate of LMM.

Mechanisms involved in melanoma invasiveness and metastasis are essential to understanding the behavior of this aggressive melanocytic skin cancer. The epithelial-mesenchymal transition (EMT) is considered fundamental for overcoming the in situ stage of melanoma and its proliferation beyond the basal membrane. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are key molecules involved in EMT about whose expression in lentigo maligna (LM) and lentigo maligna melanoma (LMM) little has been studied so far. In this article, our main aim was to review the role of TIMPs in invasiveness and aggressiveness of LM÷LMM in order to detect EMT modifications in this type of melanoma. We also presented some partial personal unpublished results. It is well established by now that progression of melanoma depends on ECM remodeling, TIMPs family being one of the most important regulators of this process. Considering the multitude of molecules involved in cancer invasiveness and their complex interaction, it is too early to analyze and to conclude upon the significance of different expression of TIMPs in LM÷LMM. We consider some correlations are needed to be done also with other consecrated histological (as Clark level, Breslow indexes, presence of ulceration, mitotic index, intratumor inflammatory infiltrate, etc.) and immunohistochemical markers [cadherins, vascular endothelial growth factor (VEGF), bcl-2, etc.] of prognosis and metastasis. In this light, we consider that our study could further clarify the significance of TIMPs expression in this specific type of melanoma.