Cancer Management and Research (Jun 2019)

Clinical genetic features and related survival implications in patients with surgically resected large-cell lung cancer

  • Wang F,
  • Lu JB,
  • Wu XY,
  • Feng YF,
  • Shao Q,
  • An X,
  • Wang HY

Journal volume & issue
Vol. Volume 11
pp. 5489 – 5499

Abstract

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Fang Wang,1,2 Jia-Bin Lu,3 Xiao-Yan Wu,2 Yan-Fen Feng,1,3 Qiong Shao,2 Xin An,4 Hai-Yun Wang1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 2Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 3Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of ChinaBackground: Large-cell lung carcinomas (LCLCs) were reclassified by the World Health Organization 2015 criteria. and remain fairly unknown at the molecular level and targeted-therapeutic options.Methods: Data of 184 lung cancer patients were retrieved from clinical records, of which 54 were found to be pathologically diagnosed as LCLC. The genetic alterations EGFR/KRAS/BRAF mutations, MET copy number, and exon 14 mutation, ALK and ROS1 rearrangements, and PDL1 expression were investigated using clinical technologies. The relationship between clinicopathologic and genetic features was analyzed, and the Kaplan–Meier method with log-rank test was used for analyzing patient survival.Results: Major events, including EGFR, KRAS, and BRAF mutations and MET copy-number gain, were found in 5.6%, 16.7%, 1.9%, and 18.5% in LCLC, respectively. No ALK or ROS1 translocation was detected. PDL1 expression in tumor cells and in tumor-infiltrating lymphocytes was observed in 24 (44.4%) and 16 (29.6%) patients. Kaplan–Meier analysis showed that patients with a KRAS mutation had ower 5-year overall survival than those with wild-type KRAS (25.4% vs 47.8%, P=0.028) and that patients with negative PDL1 stained in tumor cells but positive for tumor-infiltrating lymphocytes had significantly favorable overall survival compared to those with solitary and positive PDL1 stained in tumor cells (62.5% vs 20.6%, P=0.044).Conclusion: KRAS mutations and PDL1 expression can predict patient survival and be potential target options in LCLC.Keywords: large-cell lung cancer, driver mutations, PD-L1, KRAS

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