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

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 () (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).

CONCLUSIONS

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