E- to N-cadherin switch in melanoma is associated with decreased expression of phosphatase and tensin homolog and cancer progression.
Br J Dermatol
; 169(3): 618-28, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23662813
ABSTRACT
BACKGROUND:
Cadherin switch in melanoma, with loss of E-cadherin and upregulation of N-cadherin, is believed to underlie melanoma cell detachment from the epidermis and promotion of dermal and vascular melanoma invasion. The tumour suppressor phosphatase and tensin homolog (PTEN) has been suggested as a potential regulator of this cadherin switch.OBJECTIVES:
To study the biological and clinical implications of cadherin switch and PTEN expression in melanoma progression.METHODS:
We constructed tissue microarrays from primary tumour samples from 394 formalin-fixed paraffin-embedded melanomas diagnosed between 2001 and 2006. Median follow-up was 10 years. Tissue microarray sections were stained by immunohistochemistry for E-cadherin, N-cadherin and PTEN, and expression was analysed semiquantitatively.RESULTS:
Breslow thickness correlated strongly with reduced/absent PTEN expression (P < 0·0001), low E-cadherin expression (P < 0·0001), high N-cadherin expression (P < 0·0001) and the combination of low E-cadherin and high N-cadherin expression (cadherin switch profile; P = 0·001). There was a significant association between reduced/absent PTEN and the presence of the cadherin switch profile (P = 0·03). In univariate analyses, low E-cadherin expression significantly predicted an adverse overall relapse-free (P = 0·04), melanoma-specific (P = 0·03) and distant-metastasis-free (P = 0·01) survival; reduced/absent PTEN predicted an adverse overall relapse-free survival (P = 0·006), and the cadherin switch profile predicted adverse melanoma-specific (P = 0·005) and distant-metastasis-free (P = 0·01) survival. In multivariate analysis, the cadherin switch profile was an independent prognostic marker of melanoma-specific (P = 0·04) and distant-metastasis-free survival (P = 0·02).CONCLUSIONS:
Cadherin switch and reduced/absent PTEN expression are associated in melanoma, and both factors may play important roles in the progression of melanoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Biomarcadores Tumorais
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Caderinas
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PTEN Fosfo-Hidrolase
/
Melanoma
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Br J Dermatol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Dinamarca