Cytoplasmic iASPP Expression as a Novel Prognostic Indicator in Oral Cavity Squamous Cell Carcinoma

Abstract

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a key inhibitor of tumor suppressor p53 that is overexpressed in several human cancers; however, its role in oral cavity squamous cell carcinomas (OSCC) remains unknown. The present study investigated the prognostic role of iASPP in patients with OSCC. This study included 186 OSCC patients who underwent curative surgery at our institution between 2000 and 2011. Cytoplasmic and nuclear iASPP expression were examined separately by immunohistochemistry, and dichotomized to low and high. Clinicopathological variables associated with locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were identified by univariate and multivariate analyses. Patients were followed-up for a median period of 74 months (range 16-166 months), and 5-year LRC, DFS, and OS was 73.6, 70.2, and 75.3 %, respectively. High iASPP immunostaining reactivity was detected in the cytoplasm and nucleus in 132 (71.0 %) and 93 (50.0 %) patients, respectively. In univariate analysis, pathologic nodal metastasis, advanced overall stage III-IV, lymphovascular invasion, and cytoplasmic iASPP were significantly associated with poor LRC, DFS, and OS (p < 0.05). High-grade and positive resection margins were significant factors associated with poor DFS and OS (p < 0.02). In multivariate analysis, N classification, lymphovascular invasion, and cytoplasmic iASPP expression remained independent variables for LRC, DFS, and OS (p < 0.05). High iASPP expression in the tumor cell cytoplasm is associated with poor outcomes of OSCC patients in terms of recurrence and survival, suggesting a role for iASPP as a novel biomarker and therapeutic target for OSCC.