JCO：RET融合基因对NSCLC患者具有临床意义

近来发现，RET融合基因存在于部分非小细胞肺癌亚群中(NSCLC)。由于对此类肿瘤认识较为有限，因此上海复旦大学癌症中心的王瑞博士与陈海泉博士等人对此进行了一项研究，他们对存在RET融合基因NSCLC患者的临床病理学特征进行了确定。该文发表于2012年11月13日在线出版的《临床肿瘤学杂志》(Journal ofClinical Oncology)上。

研究人员通过逆转录聚合酶链式反应(PCR)结合实时定量PCR策略，共对936例通过手术切除治疗的NSCLC患者的RET融合基因情况进行了检测，通过免疫组织化学以及原位荧光杂交分析，对结果进行了验证。同时对633例肺腺癌患者的EGFR、KRAS、HER2、 BRAF基因突变情况以及ALK基因重排情况进行了研究。此外研究人员还收集了患者特征，包括年龄、性别、吸烟史、肿瘤分期、级别、国际肺癌研究协会/美国胸科学会/欧洲呼吸学会对肺腺癌亚型的分类、以及无复发存活期等信息。

研究人员发现，在936例NSCLC患者中，有13例患者(633例腺癌患者中有11例，24腺鳞状细胞癌患者中有2例)完全检测到RET融合基因存在。在这13例患者中，有9例患者为KIF5B-RET，3例患者为CCDC6-RET，1例患者为新发现的NCOA4-RET融合基因。存在RET融合基因的肺腺癌患者，其肿瘤分化情况较差(63.6%，对于 RET v ALK，P = .029;对于RET v EGFR， P = .007)，患者年龄偏低(≤ 60岁; 72.7%)，非吸烟者(81.8%)多发，并且患者多见实体亚型(63.6%)、瘤体较小(≤ 3 cm)、以及N2病情(54.4%)。患者平均无复发存活期为20.9个月。

王瑞博士等人认为，RET融合基因存在于1.4%的 NSCLC患者以及1.7%的肺腺癌患者中，并且该基因具有可识别的临床病理特征，因此，可考虑进一步将RET融合基因用于临床应用，并对其进行靶向治疗研究。

RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of Non–Small-Cell Lung Cancer

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.