Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Laryngoscope. 2020 Aug;130(8):1954-1960. doi: 10.1002/lary.28641. Epub 2020 Apr 10.
Most early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy. Discovery of new biomarkers are needed to improve prediction of outcome after radiotherapy and to identify potential targets for systemic targeted therapy. The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response induced by ionizing radiation.
The prognostic value of immunohistochemical expression of pATM, pChk2, and p53 were investigated in 141 patients with T1-T2 LSCC curatively treated with external beam radiotherapy. Uni- and multivariable Cox regression analyses were performed to examine the relation between expression levels of markers and local control.
Local control was significantly worse in cases with high levels of pATM (HR 2.14; 95% CI, 1.08-4.24; P = .03). No significant associations with local control were found for pChk2 and p53 expression. The association of high pATM expression with poor local control was only found for supraglottic LSCC (HR 10.9; 95% CI, 1.40-84.4; P = .02).
Our findings suggest a potential role for ATM in response to radiotherapy in early stage supraglottic LSCC and imply ATM inhibition as a possibility to improve response to radiotherapy.
NA Laryngoscope, 130: 1954-1960, 2020.
大多数早期喉鳞状细胞癌（LSCC）采用放射治疗。需要发现新的生物标志物，以提高放疗后预测结果的能力，并确定潜在的系统靶向治疗靶点。共济失调毛细血管扩张突变（ATM）基因在电离辐射诱导的 DNA 损伤反应中起着关键作用。
对 141 例 T1-T2 LSCC 患者进行了外照射放疗的治疗，检测 pATM、pChk2 和 p53 的免疫组化表达的预后价值。采用单变量和多变量 Cox 回归分析来检测标志物表达水平与局部控制之间的关系。
高 pATM 水平的病例局部控制明显较差（HR 2.14；95%CI，1.08-4.24；P = 0.03）。pChk2 和 p53 表达与局部控制无显著相关性。高 pATM 表达与局部控制不良的相关性仅见于声门上 LSCC（HR 10.9；95%CI，1.40-84.4；P = 0.02）。
我们的研究结果表明 ATM 在早期声门上 LSCC 对放射治疗的反应中可能发挥作用，并暗示 ATM 抑制作为提高放射治疗反应的可能性。
无。《喉镜》，130：1954-1960，2020。
