Pathologic features of aggressive vulvar carcinoma are associated with epithelial-mesenchymal transition.

Factors contributing to aggressive behavior in vulvar squamous cell carcinoma (vSCC) are poorly defined; however, a recent study has shown that vSCCs with an infiltrative pattern of invasion and fibromyxoid stroma are associated with worse outcomes than tumors with a pushing or nested pattern of invasion and lymphoplasmacytic stroma. Epithelial-mesenchymal transition (EMT) has been associated with tumor progression in a number of malignancies, and this study proposes that EMT contributes to tumor aggressiveness in this subset of vSCC. Immunohistochemistry was used to detect nuclear localization of β-catenin, loss of E-cadherin, and presence of vimentin in 58 cases of vSCC. The association of these phenotypic changes with pathologic features and clinical outcomes was tested using Fisher's exact and χ(2) analyses (significance at P≤.05). EMT-associated features were identified in 45 of 58 cases (78%) with 28 cases exhibiting more than one feature. Nuclear β-catenin and presence of vimentin were significantly more likely to occur in tumors with an infiltrative pattern of invasion or a fibromyxoid stromal response. Loss of E-cadherin was significantly associated with an infiltrative pattern, but not a fibromyxoid stroma. Risk for tumor recurrence was significantly increased in tumors with nuclear localization of β-catenin alone or in tumors displaying multiple EMT-associated features. These results suggest that the development of EMT may be a mechanism by which infiltrative vulvar tumors with a fibromyxoid stromal response behave more aggressively and convey worse outcomes than tumors that do not exhibit these pathologic features.