Overexpression of TWIST2 correlates with poor prognosis in Head and Neck Squamous Cell Carcinomas

Daniela Gasparotto 1 , Jerry Polesel 2 , Alessandra Marzotto 1 , Roberta Colladel 1 , Sara Piccinin 1 , Piergiorgio Modena 1 , Alessandra Grizzo 1 , Sandro Sulfaro 3 , Diego Serraino 2 , Luigi Barzan 4 , Claudio Doglioni 5 , and Roberta Maestro 1 1 Unit of Experimental Oncology 1, CRO National Cancer Institute, Aviano, Italy 2 Unit of Epidemiology and Biostatistics, CRO National Cancer Institute, Aviano, Italy 3 Unit of Pathology, Pordenone City Hospital, Pordenone, Italy 4 Unit of Otorhinolaryngology, Pordenone City Hospital, Pordenone, Italy 5 Unit of Pathology, San Raffaele Institute, Milano, Italy Received: December 19, 2011; Accepted: December 20, 2011; Published: December 22, 2011; Keywords: TWIST1, TWIST2, SNAI1, SNAI2, EMT, HNSCC Correspondence: Roberta Maestro, email: // // Abstract Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of tumors with variable presentation and clinical behavior. Despite improvements in surgical and radiation therapy techniques, the 5-year survival rate has not improved significantly over the past decades. Thus, there is an urgent need to identify novel markers that may allow for the development of personalized therapeutic approaches. In the present study we evaluated the prognostic role of the expression of genes related to the induction of epithelial mesenchymal transition (EMT). To this aim, a consecutive series of 69 HNSCC were analyzed for the expression of TWIST1, TWIST2, SNAI1, SNAI2, E-Cadherin, N-Cadherin and Vimentin. TWIST1, TWIST2, SNAI1 and SNAI2 were significantly overexpressed in HNSCC, with TWIST2, SNAI1 and SNAI2 being more markedly increased in tumors compared to normal mucosae. The expression of TWIST1 and SNAI2 was associated with upregulation of mesenchymal markers, but failed to correlate with pathological parameters or clinical behaviour. In contrast, we found that upregulation of TWIST2, which was independent of the activation of a mesenchymal differentiation program, correlated with poor differentiation grade (p=0.016) and shorter survival (p=0.025), and identifies a subset of node-positive oral cavity/pharynx cancer patients with very poor prognosis (p<0.001). Overall our study suggests that the assessment of TWIST2 expression might help to stratify HNSCC patients for risk of disease progression, pointing to TWIST2 as a potential prognostic marker.