Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma

Mengnan Zhao; Cheng Zhan; Ming Li; Xiaodong Yang; Xinyu Yang; Yong Zhang; Miao Lin; Yifeng Xia; Mingxiang Feng; Qun Wang

doi:10.21037/jtd.2017.12.68

Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma

J Thorac Dis. 2018 Jan;10(1):398-407. doi: 10.21037/jtd.2017.12.68.

Authors

Mengnan Zhao¹, Cheng Zhan¹, Ming Li^{1

2}, Xiaodong Yang¹, Xinyu Yang^{1

2}, Yong Zhang³, Miao Lin¹, Yifeng Xia^{1

4}, Mingxiang Feng¹, Qun Wang¹

Affiliations

¹ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Eight-Year Program Clinical Medicine, Grade of 2014, Shanghai Medical College, Fudan University, Shanghai 200032, China.
³ Department of Respiration, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁴ Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, USA.

Abstract

Background: The aberrant status of target genes and their associations with clinicopathologic characteristics are still unclear in primary lung adenocarcinoma.

Methods: 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.

Results: Overall, 952 (76.3%) of 1,247 patients harbored at least one target mutation or translocation: epidermal growth factor receptor (EGFR) (729, 58.5%), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (83, 6.7%), human epidermal growth factor receptor 2 (HER2) (82, 6.6%), anaplastic lymphoma kinase (ALK) (23, 1.8%), phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) (20, 1.6%), Ret proto-oncogene RET (15, 1.2%), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) (12, 1.0%), B-raf proto-oncogene (BRAF) (9, 0.7%), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) (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 KRAS mutations (both P<0.001) and PD-L1 positive tumors (P<0.001, P=0.005, respectively), and less frequent EGFR mutations (P=0.049, <0.001, respectively). In ground-glass opacity (GGO) or ground-glass nodules (GGN), there were more HER2 (P=0.033) but less EGFR (P=0.025) and PIK3CA mutations (P=0.012), and ALK translocations (P=0.014). EGFR (P<0.001), KRAS mutations (P=0.004) and PD-L1 positive tumors (P=0.046) were more frequent in older patients, while HER2 (P<0.001), ALK (P=0.005) and ROS1 aberrations (P=0.044) were less frequent. Invasive mucinous adenocarcinoma was significantly associated with KRAS and ALK aberrations (both P<0.001), while solid predominant adenocarcinoma was associated with ROS1 translocations (P=0.036) and PD-L1 expression (P<0.001). KRAS, HER2, and ALK aberrations were scarce in patients with EGFR mutations (all P<0.001), while PD-L1 positive tumors positively correlated with ALK translocations (P=0.031) and negatively correlated with HER2 mutations (P=0.019).

Conclusions: Most patients with primary lung adenocarcinoma harbored target gene aberrations. The frequency of each alteration differed in patients depending on clinicopathologic characteristics.

Keywords: Lung adenocarcinoma; epidermal growth factor receptor (EGFR); human epidermal growth factor receptor 2 (HER2); programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1); v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS).