Tan Q, Ji Y, Wang X L, Wang Z W, Qi X W, Liu Y K
Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China.
Zhonghua Bing Li Xue Za Zhi. 2023 Feb 8;52(2):124-128. doi: 10.3760/cma.j.cn112151-20220717-00614.
To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.
探讨RET融合阳性非小细胞肺癌（NSCLC）患者的临床病理特征、治疗及预后。2018年8月至2020年4月，江南大学附属医院共检索到1089例NSCLC病例。所有病例均采用多基因融合检测试剂盒（荧光PCR法）检测RET、EGFR、ALK、ROS1、KRAS、BRAF和HER2的基因状态；采用免疫组化法检测PD-L1和错配修复相关蛋白的表达。分析RET融合与患者年龄、性别、吸烟史、肿瘤分期、分级、病理类型以及PD-L1、错配修复相关蛋白表达之间的相关性。1089例NSCLC患者中，22例（2.02%）检测到RET融合阳性，其中男性11例，女性11例；中位年龄为63.5岁。腺癌20例，其中腺泡为主型腺癌（APA）11例、实体为主型腺癌（SPA）5例、贴壁为主型腺癌（LPA）4例；非角化型鳞状细胞癌和多形性肉瘤样癌各1例。RET融合阳性患者中，Ⅰ-Ⅱ期和Ⅲ-Ⅳ期分别有6例和16例，有16例发生淋巴结转移，11例发生远处转移。在RET融合阳性病例中，1例检测到HER2共突变。RET融合阳性肺癌患者中PD-L1≥1%的肿瘤比例评分是54.5%（12/22）。RET融合阳性NSCLC患者未发现错配修复蛋白表达缺陷。4例RET融合阳性患者（2例APA和2例SPA）接受普拉替尼靶向治疗，2例从该靶向治疗中获益。RET融合阳性NSCLC的组织学亚型更可能是APA或SPA。RET融合阳性NSCLC患者与临床晚期、淋巴结转移相关，可能从RET特异性抑制剂靶向治疗中获益。
