Koyama Junji, Horiike Atsushi, Yoshizawa Takahiro, Dotsu Yosuke, Ariyasu Ryo, Saiki Masafumi, Sonoda Tomoaki, Uchibori Ken, Nishikawa Shingo, Kitazono Satoru, Yanagitani Noriko, Ninomiya Hironori, Ishikawa Yuichi, Nishio Makoto
Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Division of Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
J Thorac Dis. 2019 May;11(5):1919-1928. doi: 10.21037/jtd.2019.04.102.
Recent studies have suggested a correlation between immune-related thyroid dysfunction (irTD) and the superior efficacy of anti-programmed cell death protein-1 (anti-PD-1) treatment in non-small cell lung cancer (NSCLC). Embryologically, the lung and thyroid are similar in origin, and thyroid transcription factor-1 (TTF-1) expresses in both organs, including NSCLC. We explored our hypothesis that TTF-1 expression in NSCLC might correlate with irTD incidence and anti-PD-1 treatment efficacy.
We identified 132 patients with NSCLC treated with anti-PD-1 antibody at our hospital between December 2015 and June 2017. We evaluated TTF-1 expression in tumor by immunohistochemistry using a mouse monoclonal antibody (clone 8G7G3/1, 1:100, Dako). IrTD was defined as two or more successive abnormal levels of thyroid-stimulating hormone (TSH) during anti-PD-1 treatment. We retrospectively assessed correlations between TTF-1 expression in tumor, irTD incidence, and anti-PD-1 treatment efficacy.
Of 132 patients, 67 (51%) and 65 (49%) were positive and negative for TTF-1, respectively. We observed irTD in 19 patients (6 positives and 13 negatives for TTF-1). The incidence of irTD was 9% and 20% in TTF-1-positive and TTF-1-negative NSCLCs, respectively (P=0.086). Particularly, in non-squamous (NSQ) cell carcinomas, the irTD incidence was significantly higher in patients negative for TTF-1 (30%) than in those positive for TTF-1 (9%; P=0.010), and TTF-1 expression was identified as a significant risk factor for irTD on multivariate logistic regression analysis [odds ratio (OR), 0.18; 95% confidence interval (CI), 0.05-0.59; P=0.005]. Furthermore, longer median progression-free survival (10.3 months) was observed in patients with TTF-1-negative NSCLC with irTD compared to those with TTF-1-positive NSCLC with irTD, TTF-1-positive NSCLC without irTD, and TTF-1-negative NSCLC without irTD (4.2, 1.4, and 2.4 months, respectively).
TTF-1 expression in NSCLC might correlate with irTD and anti-PD-1 treatment efficacy.
近期研究表明，免疫相关甲状腺功能障碍（irTD）与非小细胞肺癌（NSCLC）中抗程序性细胞死亡蛋白1（anti-PD-1）治疗的卓越疗效之间存在关联。从胚胎学角度来看，肺和甲状腺起源相似，甲状腺转录因子1（TTF-1）在包括NSCLC在内的这两个器官中均有表达。我们探讨了这样一个假设，即NSCLC中TTF-1的表达可能与irTD的发生率及anti-PD-1治疗疗效相关。
我们纳入了2015年12月至2017年6月期间在我院接受anti-PD-1抗体治疗的132例NSCLC患者。我们使用鼠单克隆抗体（克隆号8G7G3/1，1:100，Dako）通过免疫组织化学评估肿瘤中TTF-1的表达。irTD被定义为在anti-PD-1治疗期间促甲状腺激素（TSH）连续两次或更多次出现异常水平。我们回顾性评估了肿瘤中TTF-1表达、irTD发生率与anti-PD-1治疗疗效之间的相关性。
132例患者中，TTF-1阳性者67例（51%），阴性者65例（49%）。我们观察到19例患者发生irTD（TTF-1阳性6例，阴性13例）。TTF-1阳性和阴性的NSCLC患者中irTD的发生率分别为9%和20%（P = 0.086）。特别地，在非鳞状（NSQ）细胞癌中，TTF-1阴性患者的irTD发生率（30%）显著高于TTF-1阳性患者（9%；P = 0.010），并且在多因素逻辑回归分析中，TTF-1表达被确定为irTD的一个显著危险因素[比值比（OR），0.18；95%置信区间（CI）：0.05 - 0.59；P = 0.005]。此外，与TTF-1阳性且发生irTD的NSCLC患者、TTF-1阳性且未发生irTD的NSCLC患者以及TTF-1阴性且未发生irTD的NSCLC患者相比，TTF-1阴性且发生irTD的NSCLC患者的中位无进展生存期更长（分别为10.3个月、4.2个月、1.4个月和2.4个月）。
NSCLC中TTF-1的表达可能与irTD及anti-PD-1治疗疗效相关。
