RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of Non-Small-Cell Lung Cancer
RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of Non-Small-Cell Lung Cancer
复制标题
RET 融合定义了非小细胞肺癌的独特分子和临床病理亚型。
DOI：
10.1200/jco.2012.44.1477
复制
发表时间：
2012-12-10
影响因子：
45.3
通讯作者：
Chen, Haiquan
中科院分区：
文献类型：
--
作者：
Wang, Rui;Hu, Haichuan;Chen, Haiquan
目的
RET融合基因最近在非小细胞肺癌（NSCLC）的一个子集中被描述。由于我们对这些肿瘤的了解有限，本研究旨在确定携带RET融合基因的NSCLC患者的临床病理特征。
患者和方法
我们使用逆转录聚合酶链反应（PCR）加定量实时PCR策略，并使用免疫组化和荧光原位杂交检测验证936例手术切除的NSCLC患者的RET融合基因。还研究了633例肺腺癌的EGFR、KRAS、HER 2和BRAF突变以及ALK重排。收集患者特征，包括年龄、性别、吸烟史、分期、分级、国际肺癌研究协会/美国胸科学会/欧洲呼吸学会肺腺癌亚型分类和无复发生存率。
结果
在936例NSCLC患者中，仅在13例患者中检测到RET融合基因（633例腺癌患者中的11例和24例腺鳞癌患者中的2例）。在13例患者中，9例患者接受KIF 5 B-RET，3例患者接受CCDC 6-RET，1例患者接受新型NCOA 4-RET融合。携带RET融合基因的肺腺癌患者的低分化肿瘤更多（63.6%; RET v ALK P = .029，RET v EGFR P = .007），有年轻化趋势（≤ 60岁; 72.7%）和从不吸烟者（81.8%），有实体亚型（63.6%）和较小肿瘤（≤ 3 cm）伴N2疾病（54.4%）。中位无复发生存期为20.9个月。
结论
RET融合发生在1.4%的非小细胞肺癌和1.7%的肺腺癌中，具有可识别的临床病理特征，值得进一步的临床考虑和靶向治疗研究。
PURPOSE
The RET fusion gene has been recently described in a subset of non-small-cell lung cancers (NSCLCs). Because we have limited knowledge about these tumors, this study was aimed at determining the clinicopathologic characteristics of patients with NSCLC harboring the RET fusion gene.
PATIENTS AND METHODS
We examined the RET fusion gene in 936 patients with surgically resected NSCLC using a reverse transcriptase polymerase chain reaction (PCR) plus quantitative real-time PCR strategy, with validation using immunohistochemical and fluorescent in situ hybridization assays. A subset of 633 lung adenocarcinomas was also studied for EGFR, KRAS, HER2, and BRAF mutations, as well as ALK rearrangements. Patient characteristics, including age, sex, smoking history, stage, grade, International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of subtypes of lung adenocarcinoma, and relapse-free survival, were collected.
RESULTS
Of 936 patients with NSCLC, the RET fusion gene was exclusively detected in 13 patients (11 of 633 patients with adenocarcinomas and two of 24 patients with adenosquamous cell carcinomas). Of the 13 patients, nine patients had KIF5B-RET, three patients had CCDC6-RET, and one patient had a novel NCOA4-RET fusion. Patients with lung adenocarcinomas with RET fusion gene had more poorly differentiated tumors (63.6%; P = .029 for RET v ALK, P = .007 for RET v EGFR), with a tendency to be younger (≤ 60 years; 72.7%) and never-smokers (81.8%) and to have solid subtype (63.6%) and a smaller tumor (≤ 3 cm) with N2 disease (54.4%). The median relapse-free survival was 20.9 months.
CONCLUSION
RET fusion occurs in 1.4% of NSCLCs and 1.7% of lung adenocarcinomas and has identifiable clinicopathologic characteristics, warranting further clinical consideration and targeted therapy investigation.