Abstract 1481: Expression profiling of β-catenin, E-cadherin and Slug in the development and progression of vulvar carcinoma.

Introduction: Vulvar squamous cell carcinoma (VSCC) is usually diagnosed in a stage still amenable to potentially curative treatments. However, 30-50% of patients present metastatic disease at diagnosis. During metastatic progression, tumor cells lose cell-cell adhesion, detach from the primary site and invade the basement membrane characterizing the epithelial-mesenchymal transition phenomenon. Loss of E-cadherin and β-catenin adhesion proteins represents the main marker of this process and the key downstream effectors in the Wnt-Akt signalling pathway. The reduction of membranous expression and also the nuclear translocation of β-catenin induce up-regulation of Slug and may represent a critical early event in tumor invasion and metastasis. However, the role of these proteins in VSCC has not been elucidated yet. Aim: Evaluate protein expression of E-cadherin, β-catenin, Slug in VSCC at the invasive front compare with central tumor and associate their expression with clinical data collected from patients’ medical records and the presence or not of HPV infection. Material and Methods: 100 cases of VSCC diagnosed between 1979 and 2006 were selected from the Anatomic Pathology Department of AC Camargo Hospital, Brazil. For HPV detection and typing, linear array HPV genotyping in test was used. Immunoreactivity for E-cadherin, β-catenin and Slug was performed using the Benchmark, Ventana®. All statistical analyses were performed with SPSS 17.0. The association between experimental findings and clinicopathological variables was analyzed with the X2-test for categorical data and survival rates were calculated by Kaplan-Meier test. Results: Diminished β-catenin and E-caderin expression was observed in invasive front compared to the central tumor (p = 0.013 and p0.001, respectively). However, no significant difference between nuclear staining of Slug in invasive front compared to the central tumor was observed. Concerning HPV positive, lower expression of β-catenin and higher expression of Slug we observed in HPV positive cases (p=0.002 and p=0.007, respectively). The immunoreactivity of β-catenin and Slug did not correlate significantly with inflammatory infiltration, vascular invasion, perineural invasion, and metastasis. However, E-caderin expression was correlated significantly with vascular invasion (p=0.024). Patients with low levels of β-catenin and high levels of Slug expression in both central and front tumor components had lower overall survival than the other groups (p = 0.004 and p=0.002, respectively). Conclusion: Evaluating the E-cadherin, β-catenin and Slug expression proteins at the front of tumor invasion may represent an important tool in establishing prognosis of patients with vulvar carcinoma. Citation Format: Lara Santana Rodrigues, Andre Lavorato, Beatriz de Melo Maia, Glauco Baiocchi, Monica Stiepcich, Fernanda Bertonha, Rafael Malagoli. Expression profiling of β-catenin, E-cadherin and Slug in the development and progression of vulvar carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1481. doi:10.1158/1538-7445.AM2013-1481