Involvement of E-cadherin, beta-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma.
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.


OBJECTIVE
To investigate whether dysregulation of cell motility (Cdc42 expression), escaping the control of cell-cell and cell-matrix interactions (E-cadherin, beta-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, beta-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 beta-catenin was increased in the patients who had died compared with disease-free individuals, while membrane expression of beta-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.
Tucci
M G
MG
U.O. Dermatologia, INRCA-IRCCS, Via della Montagnola 164, Ancona, Italy.
Lucarini
G
G
Brancorsini
D
D
Zizzi
A
A
Pugnaloni
A
A
Giacchetti
A
A
Ricotti
G
G
Biagini
G
G
D000328:Adult; D000368:Aged; D015820:Cadherins / Q000502:physiology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008545:Melanoma / Q000209:etiology*; D008875:Middle Aged; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000502:physiology*; D012878:Skin Neoplasms / Q000209:etiology*; D051176:beta Catenin / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*
D015820:Cadherins; D019718:Receptors, CXCR4; D051176:beta Catenin; D020764:cdc42 GTP-Binding Protein