Morita Shinya, Kano Satoshi, Hatanaka Kanako C, Hatanaka Yutaka, Suzuki Takayoshi, Fukuda Atsushi, Hoshino Kimiko, Fujiwara Keishi, Nakamaru Yuji, Homma Akihiro
Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Japan.
Int J Clin Oncol. 2022 Sep;27(9):1394-1403. doi: 10.1007/s10147-022-02191-z. Epub 2022 Jun 14.
External auditory canal squamous cell carcinoma (EACSCC) is a rare form of malignant tumor. Due to the extremely limited understanding of the genomic landscape in EACSCC, the association between gene mutations and clinicopathologic features remains unclear. This study aimed to explore somatic gene mutations associated with the clinicopathological features in patients with EACSCC, and to identify the candidate gene mutations for predicting survival outcome in EACSCC.
Twenty-two tissue samples obtained from patients with EACSCC were analyzed for genetic mutations based on targeted next-generation sequencing and genetic expression based on IHC staining to investigate the driver of tumorigenesis and/or the candidates of genes for predicting clinical outcome in EACSCC.
Gene alterations were most frequently observed in TP53 (59.1%), followed by CREBBP (9.1%). TP53 mutations showed significant correlation with T classification (P = 0.027) and p53 expression phenotype (P < 0.001). The 5-year overall survival (OS) rates for EACSCC patients with TP53 mutations and wild-type TP53 were 45.0% and 75.0%, respectively. Multivariable analysis using the Cox proportional hazards model demonstrated that TP53 mutations were independent predictors of OS rates for EACSCC patients (P = 0.007).
This study has suggested that TP53 mutations have potential for use as a biomarker for identifying individuals at high risk of developing tumors and for predicting survival outcome in EACSCC. IHC staining for p53 might play a useful role as screening tool for detecting TP53 mutations in patients with EACSCC.
外耳道鳞状细胞癌（EACSCC）是一种罕见的恶性肿瘤形式。由于对EACSCC基因组格局的了解极为有限，基因突变与临床病理特征之间的关联仍不清楚。本研究旨在探讨与EACSCC患者临床病理特征相关的体细胞基因突变，并确定预测EACSCC生存结局的候选基因突变。
对22例EACSCC患者的组织样本进行靶向二代测序分析基因突变，并通过免疫组化染色分析基因表达，以研究EACSCC的肿瘤发生驱动因素和/或预测临床结局的候选基因。
基因改变最常见于TP53（59.1%），其次是CREBBP（9.1%）。TP53突变与T分期（P = 0.027）和p53表达表型（P < 0.001）显著相关。TP53突变的EACSCC患者和野生型TP53患者的5年总生存率分别为45.0%和75.0%。使用Cox比例风险模型进行的多变量分析表明，TP53突变是EACSCC患者总生存率的独立预测因素（P = 0.007）。
本研究表明，TP53突变有可能作为一种生物标志物，用于识别EACSCC中发生肿瘤的高风险个体并预测生存结局。p53免疫组化染色可能作为检测EACSCC患者TP53突变筛查工具发挥有用作用。
