甲状腺转录因子 1 阴性表达定义了肺腺癌的一个不利亚组。

Negative Thyroid Transcription Factor 1 Expression Defines an Unfavorable Subgroup of Lung Adenocarcinomas.

机构信息

*Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; †Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; ‡Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; and §Section of Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.

出版信息

J Thorac Oncol. 2015 Oct;10(10):1444-50. doi: 10.1097/JTO.0000000000000626.

DOI:10.1097/JTO.0000000000000626

PMID:26200450

Abstract

INTRODUCTION

Thyroid transcription factor 1 (TTF1) is a master regulator of pulmonary differentiation that is downregulated in a subset of lung adenocarcinoma, of which the clinicopathologic characteristics were not fully clarified.

METHODS

One thousand forty-two lung adenocarcinoma patients who underwent surgery were investigated for clinic characteristics, histologic subtyping, and spectrum of well-identified driver mutations. TTF1 expression was correlated with these clinicopathologic factors and survival.

RESULTS

Compared with TTF1 positive (TTF1+) patients, the 133 negative individuals (12.8%, TTF1-) were more likely to be male (p = 0.006) and heavy smokers (p = 0.002) who had larger tumor size (p < 0.001) and more advanced disease stage (p < 0.001). TTF1- presented more in solid and invasive mucinous-predominant carcinomas (both p < 0.001), whereas TTF1+ was identified in 100% patients with adenocarcinoma in situ, minimally invasive and lepidic-predominant adenocarcinomas. The TTF1- tumors harbored the known driver mutations in significantly low frequency compared with TTF1+ adenocarcinomas (57.8% versus 78.1%, p < 0.001), especially in epidermal growth factor receptor (EGFR) mutations (37.6% versus 60.7%, p < 0.001). There was no significant difference in recurrence-free survival between the TTF1- and TTF1+ patients, either for the whole cohort or stratified by pathologic stage, or among the driver mutation-defined subsets. However, recurrence of multiple metastases was more likely to occur in patients with TTF1- adenocarcinomas (88.1% versus 32.4%, p < 0.001). Multivariate analysis revealed that TTF1- independently predicted both poor postrecurrence survival (hazard ratio = 1.664; 95% confidence interval , 1.097-2.524; p = 0.017) and unfavorable overall survival (hazard ratio = 1.553; 95% confidence interval , 1.013-2.381; p = 0.043).

CONCLUSIONS

TTF1- correlated with solid and invasive mucinous subtypes of lung adenocarcinoma and lower frequency of EGFR mutations. It defines a subgroup of lung adenocarcinomas with unfavorable outcomes.

摘要

简介

甲状腺转录因子 1（TTF1）是肺分化的主要调节因子，在一部分肺腺癌中下调，其临床病理特征尚未完全阐明。

方法

对 1042 例接受手术的肺腺癌患者进行临床特征、组织学亚型和明确驱动突变谱的研究。TTF1 表达与这些临床病理因素和生存相关。

结果

与 TTF1 阳性（TTF1+）患者相比，133 例 TTF1 阴性（12.8%，TTF1-）患者更可能为男性（p = 0.006）和重度吸烟者（p = 0.002），肿瘤体积更大（p < 0.001），疾病分期更晚（p < 0.001）。TTF1-更常见于实性和侵袭性黏液型为主的癌（均 p < 0.001），而 TTF1+则见于 100%的原位腺癌、微浸润和贴壁型为主的腺癌患者。与 TTF1+腺癌相比，TTF1-肿瘤中已知的驱动突变频率明显较低（57.8%对 78.1%，p < 0.001），尤其是表皮生长因子受体（EGFR）突变（37.6%对 60.7%，p < 0.001）。在无复发生存方面，TTF1-和 TTF1+患者之间没有差异，无论是在整个队列中还是在病理分期分层中，还是在驱动突变定义的亚组中。然而，TTF1-腺癌患者更有可能出现多个转移的复发（88.1%对 32.4%，p < 0.001）。多变量分析显示，TTF1-独立预测复发后生存不良（风险比=1.664；95%置信区间，1.097-2.524；p = 0.017）和总体生存不良（风险比=1.553；95%置信区间，1.013-2.381；p = 0.043）。