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

M. G. Tucci, G. Lucarini, D. Brancorsini, A. Zizzi, A. Pugnaloni, A. Giacchetti, G. Ricotti, G. Biagini

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1212-1216
Number of pages5
JournalBritish Journal of Dermatology
Volume157
Issue number6
DOIs
Publication statusPublished - Dec 2007

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Catenins
Cadherins
Melanoma
Cell Movement
Skin
Fatal Outcome
Neoplasm Metastasis
Neoplasms
Chemokine Receptors
Cell Communication
Membranes

Keywords

  • β-catenin
  • Cdc42
  • Cutaneous melanoma
  • CXCR4
  • E-cadherin

ASJC Scopus subject areas

  • Dermatology

Cite this

Involvement of E-cadherin, β-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma. / Tucci, M. G.; Lucarini, G.; Brancorsini, D.; Zizzi, A.; Pugnaloni, A.; Giacchetti, A.; Ricotti, G.; Biagini, G.

In: British Journal of Dermatology, Vol. 157, No. 6, 12.2007, p. 1212-1216.

Research output: Contribution to journalArticle

Tucci, M. G. ; Lucarini, G. ; Brancorsini, D. ; Zizzi, A. ; Pugnaloni, A. ; Giacchetti, A. ; Ricotti, G. ; Biagini, G. / Involvement of E-cadherin, β-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma. In: British Journal of Dermatology. 2007 ; Vol. 157, No. 6. pp. 1212-1216.
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T1 - Involvement of E-cadherin, β-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma

AU - Tucci, M. G.

AU - Lucarini, G.

AU - Brancorsini, D.

AU - Zizzi, A.

AU - Pugnaloni, A.

AU - Giacchetti, A.

AU - Ricotti, G.

AU - Biagini, G.

PY - 2007/12

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N2 - 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.

AB - 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.

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