Clinicopathologic significance of dysadherin expression in cutaneous malignant melanoma: immunohistochemical analysis of 115 patients

Cancer. 2005 Apr 15;103(8):1693-700. doi: 10.1002/cncr.20984.

Abstract

Background: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti-cell-cell adhesion function and down-regulates E-cadherin.

Methods: Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors.

Results: Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001).

Conclusions: Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Cadherins / metabolism
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Adhesion
  • Cell Membrane / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Ion Channels
  • Lymphatic Metastasis / pathology
  • Male
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Membrane Glycoproteins / metabolism*
  • Microfilament Proteins
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Prognosis
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Cadherins
  • FXYD5 protein, human
  • Ion Channels
  • Membrane Glycoproteins
  • Microfilament Proteins
  • Neoplasm Proteins