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

Background: Epithelial-to-mesenchymal transition (EMT) still remains an obscure event in vulvar squamous cell carcinoma (VSCC). Methods: Immunohistochemistry (IHC) expression of E-cadherin, beta-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 beta-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 beta-catenin and high Slug, Snail and Twist expression was associated with HPV-negative tumours. Moreover, beta-catenin lower expression associated with gain in Slug expression predicts a subgroup with worst outcome (P=0.001). Lower expression of beta-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 beta-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 beta-catenin in invasive tumour front is a key issue for establishing prognosis of vulva cancer.