Zhao Mengnan, Zhan Cheng, Li Ming, Yang Xiaodong, Yang Xinyu, Zhang Yong, Lin Miao, Xia Yifeng, Feng Mingxiang, Wang Qun
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Eight-Year Program Clinical Medicine, Grade of 2014, Shanghai Medical College, Fudan University, Shanghai 200032, China.
J Thorac Dis. 2018 Jan;10(1):398-407. doi: 10.21037/jtd.2017.12.68.
The aberrant status of target genes and their associations with clinicopathologic characteristics are still unclear in primary lung adenocarcinoma.
The common mutations and translocations of nine target genes were evaluated in 1,247 specimens of surgically-resected primary lung adenocarcinoma. Immunohistochemistry was used to analyze the expressions of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in 731 specimens. The frequency of the aberrations and their associations with clinicopathologic characteristics were analyzed.
Overall, 952 (76.3%) of 1,247 patients harbored at least one target mutation or translocation: epidermal growth factor receptor () (729, 58.5%), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog () (83, 6.7%), human epidermal growth factor receptor 2 () (82, 6.6%), anaplastic lymphoma kinase ( (23, 1.8%), phosphoinositide-3-kinase catalytic alpha polypeptide () (20, 1.6%), Ret proto-oncogene (15, 1.2%), ROS proto-oncogene 1 receptor tyrosine kinase () (12, 1.0%), B-raf proto-oncogene () (9, 0.7%), neuroblastoma RAS viral (v-ras) oncogene homolog () (3, 0.2%). Fourteen (1.9%) of 731 patients were PD-1 positive and 95 (13.0%) were PD-L1 positive in tumor cells. In men and smokers, there were more frequent mutations (both P<0.001) and PD-L1 positive tumors (P<0.001, P=0.005, respectively), and less frequent mutations (P=0.049, <0.001, respectively). In ground-glass opacity (GGO) or ground-glass nodules (GGN), there were more (P=0.033) but less (P=0.025) and mutations (P=0.012), and translocations (P=0.014). (P<0.001), mutations (P=0.004) and PD-L1 positive tumors (P=0.046) were more frequent in older patients, while (P<0.001), (P=0.005) and aberrations (P=0.044) were less frequent. Invasive mucinous adenocarcinoma was significantly associated with and aberrations (both P<0.001), while solid predominant adenocarcinoma was associated with translocations (P=0.036) and PD-L1 expression (P<0.001). and aberrations were scarce in patients with mutations (all P<0.001), while PD-L1 positive tumors positively correlated with translocations (P=0.031) and negatively correlated with mutations (P=0.019).
Most patients with primary lung adenocarcinoma harbored target gene aberrations. The frequency of each alteration differed in patients depending on clinicopathologic characteristics.
在原发性肺腺癌中，靶基因的异常状态及其与临床病理特征的关联仍不明确。
对1247例手术切除的原发性肺腺癌标本中的9个靶基因的常见突变和易位进行评估。采用免疫组织化学方法分析731例标本中程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）的表达。分析异常的频率及其与临床病理特征的关联。
总体而言，1247例患者中有952例（76.3%）至少存在一种靶基因突变或易位：表皮生长因子受体（EGFR）（729例，58.5%）、v-Ki-ras2 Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）（83例，6.7%）、人表皮生长因子受体2（HER2）（82例，6.6%）、间变性淋巴瘤激酶（ALK）（23例，1.8%）、磷酸肌醇-3-激酶催化α多肽（PIK3CA）（20例，1.6%）、Ret原癌基因（RET）（15例，1.2%）、ROS原癌基因1受体酪氨酸激酶（ROS1）（12例，1.0%）、B-raf原癌基因（BRAF）（9例，0.7%）、神经母细胞瘤RAS病毒（v-ras）癌基因同源物（NRAS）（3例，0.2%）。731例患者中有14例（1.9%）PD-1阳性，95例（13.0%）肿瘤细胞中PD-L1阳性。在男性和吸烟者中，EGFR突变（均P<0.001）和PD-L1阳性肿瘤更常见（分别为P<0.001、P=0.005），而KRAS突变较少见（分别为P=0.049、P<0.001）。在磨玻璃影（GGO）或磨玻璃结节（GGN）中，EGFR突变更多（P=0.033），但KRAS和NRAS突变较少（分别为P=0.025、P=0.012），且ALK易位较少（P=0.014）。在老年患者中，EGFR突变（P<0.001）、PIK3CA突变（P=0.004）和PD-L1阳性肿瘤更常见（P=0.046），而KRAS突变（P<0.001）、NRAS突变（P=0.005）和ALK异常较少见（P=0.044）。浸润性黏液腺癌与EGFR和PIK3CA异常显著相关（均P<0.001），而实性为主型腺癌与ALK易位（P=0.036）和PD-L1表达相关（P<0.001）。在有EGFR突变的患者中，KRAS和NRAS异常少见（均P<0.001），而PD-L1阳性肿瘤与ALK易位呈正相关（P=0.031），与KRAS突变呈负相关（P=0.019）。
大多数原发性肺腺癌患者存在靶基因异常。根据临床病理特征，患者中每种改变的频率有所不同。
