Lapke Nina, Lu Yen-Jung, Liao Chun-Ta, Lee Li-Yu, Lin Chien-Yu, Wang Hung-Ming, Ng Shu-Hang, Chen Shu-Jen, Yen Tzu-Chen
ACT Genomics, Taipei, Taiwan, ROC.
Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
Oncotarget. 2016 Jul 12;7(28):44194-44210. doi: 10.18632/oncotarget.9925.
TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients.
TP53突变与口腔鳞状细胞癌（OSCC）患者生存率降低有关。然而，不同类型TP53突变的影响仍不明确。在此，我们证明，在345例OSCC患者队列中，与野生型TP53相比，TP53 DNA结合域错义突变（DBD错义突变）与疾病特异性生存率（DSS）降低相关（P = 0.002）。相比之下，携带所有其余TP53突变的患者的DSS与野生型TP53患者观察到的情况无差异（P = 0.955）。我们的TP53突变分类方法在区分低风险和高风险患者方面优于先前报道的方法（破坏性、截短性、进化作用评分、L2/L3/LSH中的突变）。当与传统临床病理因素联合分析时，TP53 DBD错义突变与晚期AJCC T和N分类以及存在包膜外扩散一起，是DSS缩短的独立预后因素（P = 0.014）。一个包含这四个独立预后因素的评分系统能够将患者可靠地分层为不同的风险组（高风险患者，16.2%）。我们的结果证明了TP53 DBD错义突变与临床病理因素相结合对改善OSCC患者预后分层的有用性。
