title: Epithelial-mesenchymal transition-like events in vulvar cancer and its relation with HPV.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, Rua Professor Antônio Prudente, 211, 1 andar, prédio Hilda Jacob, Liberdade-São Paulo 01509 010, Brazil.
authors.forename: I S
authors.initials: IS
authors.lastname: Rodrigues
authors.forename: A M
authors.initials: AM
authors.lastname: Lavorato-Rocha
authors.forename: B
authors.initials: B
authors.lastname: de M Maia
authors.forename: M M A
authors.initials: MM
authors.lastname: Stiepcich
authors.forename: F M
authors.initials: FM
authors.lastname: de Carvalho
authors.forename: G
authors.initials: G
authors.lastname: Baiocchi
authors.forename: F A
authors.initials: FA
authors.lastname: Soares
authors.forename: R M
authors.initials: RM
authors.lastname: Rocha
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000096:biosynthesis; D030361:Papillomavirus Infections / Q000378:metabolism*; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D051879:Twist-Related Protein 1 / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis; D014846:Vulvar Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; D051176:beta Catenin