Epithelial-mesenchymal transition-like events in vulvar cancer and its relation with HPV

Br J Cancer. 2013 Jul 9;109(1):184-94. doi: 10.1038/bjc.2013.273. Epub 2013 Jun 18.


Background: Epithelial-to-mesenchymal transition (EMT) still remains an obscure event in vulvar squamous cell carcinoma (VSCC).

Methods: Immunohistochemistry (IHC) expression of E-cadherin, β-catenin, Snail, Slug, Twist and Vimentin was analysed in 87 VSCC, controlled for human papillomavirus (HPV) positivity, considering tumour front and central tumour as different morphological categories from the same tumour.

Results: Lower β-catenin and higher Vimentin expression was associated with invasive front when compared with the central tumour (P=0.013 and P≤0.001, respectively). Higher expression of E-cadherin in central tumour was significantly related to absence of vascular and perineural invasion, lower invasion depth and ≥2 lymph node involvement. Loss of β-catenin and high Slug, Snail and Twist expression was associated with HPV-negative tumours. Moreover, β-catenin lower expression associated with gain in Slug expression predicts a subgroup with worst outcome (P=0.001). Lower expression of β-catenin in both central tumour and invasive front correlated with lower overall survival (P=0.021 and P=0.011, respectively). Also, multivariate analysis showed that lower β-catenin expression was independently associated with poorer outcome (P=0.044).

Conclusion: Human papillomavirus-related tumours show better prognosis and outcome; besides, they do not progress through EMT phenomenon. Immunohistochemical analysis of β-catenin in invasive tumour front is a key issue for establishing prognosis of vulva cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alphapapillomavirus
  • Biomarkers, Tumor / metabolism*
  • Cadherins / biosynthesis
  • Epithelial-Mesenchymal Transition*
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Nuclear Proteins / biosynthesis
  • Papillomavirus Infections / metabolism*
  • Prognosis
  • Snail Family Transcription Factors
  • Transcription Factors / biosynthesis
  • Twist-Related Protein 1 / biosynthesis
  • Vimentin / biosynthesis
  • Vulvar Neoplasms / metabolism
  • Vulvar Neoplasms / pathology
  • Vulvar Neoplasms / virology*
  • beta Catenin / biosynthesis


  • Biomarkers, Tumor
  • Cadherins
  • Nuclear Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1
  • Vimentin
  • beta Catenin