Involvement of E‐cadherin, β‐catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma

Summary Background  A key event in cancer metastasis is the migration of tumour cells from their original location to a secondary site. The development of melanoma may be viewed as a consequence of the disruption of homeostatic mechanisms in the skin of the original site. Objectives  To investigate whether dysregulation of cell motility (Cdc42 expression), escaping the control of cell–cell and cell–matrix interactions (E-cadherin, β-catenin expression), enhances melanoma progression, and whether chemokine receptors (CXCR4) mediate cell migration and activation during invasion and metastasis development. Methods  The immunohistochemical expression of Cdc42, E-cadherin, β-catenin and CXCR4 was investigated in 30 patients with surgically treated nodular melanoma, 18 alive and disease free and 12 with a fatal outcome due to metastatic disease. Results  E-cadherin expression was significantly reduced (P < 0·05) and cytoplasmic β-catenin was increased in the patients who had died compared with disease-free individuals, while membrane expression of β-catenin was similar in the two groups. Patients with fatal outcome had increased Cdc42 (P < 0·01) and CXCR4 (P < 0·05). In this group a positive correlation was found between melanocytic Cdc42 expression and Breslow thickness (r = 0·598, P < 0·05) and between CXCR4 expression and Breslow thickness (r = 0·583, P < 0·05). Conclusions  Findings suggest that primary cutaneous melanoma with a high Breslow thickness is characterized by tumour cells with high motility and invasion ability, in line with the hypothesis that low E-cadherin levels and overexpression of Cdc42 and CXCR4 could be prognostic markers of poor outcome.