Kim Ji Won, Roh Jong-Lyel, Park Yangsoon, Cho Kyung-Ja, Choi Seung-Ho, Nam Soon Yuhl, Kim Sang Yoon
Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Ann Surg Oncol. 2015 Feb;22(2):662-9. doi: 10.1245/s10434-014-4003-0. Epub 2014 Aug 23.
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.
p53凋亡刺激蛋白抑制剂(iASPP)是肿瘤抑制因子p53的关键抑制剂,在多种人类癌症中过表达;然而,其在口腔鳞状细胞癌(OSCC)中的作用尚不清楚。本研究调查了iASPP在OSCC患者中的预后作用。
本研究纳入了2000年至2011年间在我院接受根治性手术的186例OSCC患者。通过免疫组织化学分别检测细胞质和细胞核中iASPP的表达,并分为低表达和高表达。通过单因素和多因素分析确定与局部区域控制(LRC)、无病生存期(DFS)和总生存期(OS)相关的临床病理变量。
患者的中位随访期为74个月(范围16 - 166个月),5年LRC、DFS和OS分别为73.6%、70.2%和75.3%。分别在132例(71.0%)和93例(50.0%)患者的细胞质和细胞核中检测到高iASPP免疫染色反应性。在单因素分析中,病理淋巴结转移、晚期III - IV期、淋巴管浸润和细胞质iASPP与LRC、DFS和OS不良显著相关(p < 0.05)。高分级和切缘阳性是与DFS和OS不良相关的显著因素(p < 0.02)。在多因素分析中,N分类、淋巴管浸润和细胞质iASPP表达仍然是LRC、DFS和OS的独立变量(p < 0.05)。
肿瘤细胞细胞质中iASPP的高表达与OSCC患者在复发和生存方面的不良预后相关,提示iASPP作为OSCC的一种新型生物标志物和治疗靶点的作用。