Metastatic pathways in patients with cutaneous melanoma

Abstract

Summary Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies.

Histamine therapeutic efficacy in metastatic melanoma: Role of histamine H4 receptor agonists and opportunity for combination with radiation

“…Lymphogenous and hematogenous metastasis can occur in melanoma [47]. In this sense, H 4 R agonists together with a reduction of tumor volume, produce changes in the morphology and the number of vessels.…”

“…Metastasis is a multistep process, which includes proliferation, neovascularization, immune system evasion, lymphangiogenesis, invasion, circulation, embolism, extravasation and colonization [47]. Therefore, we consider that all these processes are potential mechanisms that could be involved in the reduction of metastatic spread along with results obtained in in vitro experiments, in which histamine and H 4 R agonists reduce cell proliferation, increase tumor cell senescence and differentiation and interestingly decrease the gelatinolytic activity of MMP-2, a regulator of tissue invasion.…”

Sentinel bruising as a presentation of metastatic melanoma

“…First, patients with head and neck primary melanomas have a higher frequency of developing direct distant metastases compared with those on other sites 24. This may reflect that NRAS mutations are more common in areas of chronic sun exposure, with some evidence suggesting that NRAS and BRAF mutant tumours may behave more aggressively than wild-type tumours—but the extent to which this is independent of anatomical location is unclear 425 although results from a different study were discordant 24.…”

“…Cutaneous melanoma can metastasise to any organ 4. The first presentation of metastasis is to the skin in 2%–8% of cases (cutaneous malignant melanoma metastases [CMMM]) 5.…”

MicroRNA-Directed Cancer Therapies: Implications in Melanoma Intervention

“…Metastasis of melanoma tumors to distal organs including the brain is a complex process requiring several stages from local tumor invasion to intra-and extravasation leading to the formation of macrometastases, which is the major cause of skin cancer-related mortality in the United States (Adler et al, 2017;Westphal et al, 2017) (Table 4). Several factors or signaling pathways have been shown to drive melanoma cell migration and invasion leading to metastasis including FSCN1, basigin, b3-integrin, GALANT7, MARCKS, c-MET, STAT3, PTEN, and NFkB1 (Muramatsu and Miyauchi, 2003;Boukerche et al, 2007;Estrada-Bernal et al, 2009;Elson-Schwab et al, 2010;Yang et al, 2011;Chattopadhyay et al, 2012;Liu et al, 2013b;Li et al, 2016).…”