1.William D. Travis EB, Allen P. Burke, Alexander Marx, Andrew G. Nicholson. WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart. Lyon: International Agency for Research on Cancer (IARC); 2015.
2.Reck M, Heigener DF, Mok T, Soria JC, Rabe KF. Management of non-small-cell lung cancer: recent developments. Lancet. 2013;382:709–719.
3.Yap TA, Gerlinger M, Futreal PA, Pusztai L, Swanton C. Intratumor heterogeneity: seeing the wood for the trees. Science translational medicine. 2012;4:127ps110.
4.Cai YR, Dong YJ, Wu HB, et al. Micropapillary: A component more likely to harbour heterogeneous EGFR mutations in lung adenocarcinomas. Sci Rep. 2016;6:23755.
5.Dong ZY, Zhai HR, Hou QY, et al. Mixed Responses to Systemic Therapy Revealed Potential Genetic Heterogeneity and Poor Survival in Patients with Non-Small Cell Lung Cancer. The oncologist. 2017;22:61–69.
6.Liedtke C, Broglio K, Moulder S, et al. Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 2009;20:1953–1958.
7.Yoshizawa A, Sumiyoshi S, Sonobe M, et al. Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer. 2013;8:52–61.
8.Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Annals of surgical oncology. 2010;17:1471–1474.
9.Gonzalez-Garcia I, Sole RV, Costa J. Metapopulation dynamics and spatial heterogeneity in cancer. Proceedings of the National Academy of Sciences of the United States of America. 2002;99:13085–13089.
10.De Oliveira Duarte Achcar R, Nikiforova MN, Yousem SA. Micropapillary lung adenocarcinoma: EGFR, K-ras, and BRAF mutational profile. American journal of clinical pathology. 2009;131:694–700.
11.Tsutsumida H, Nomoto M, Goto M, et al. A micropapillary pattern is predictive of a poor prognosis in lung adenocarcinoma, and reduced surfactant apoprotein A expression in the micropapillary pattern is an excellent indicator of a poor prognosis. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 2007;20:638–647.
12.Yoshizawa A, Motoi N, Riely GJ, et al. Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 2011;24:653–664.
13.Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature reviews. Cancer. 2012;12:252–264.
14.Yoshimura K, Inoue Y, Karayama M, et al. Heterogeneity analysis of PD-L1 expression and copy number status in EBUS-TBNA biopsy specimens of non-small cell lung cancer: Comparative assessment of primary and metastatic sites. Lung cancer. 2019;134:202–209.
15.D’Incecco A, Andreozzi M, Ludovini V, et al. PD–1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. British journal of cancer. 2015;112:95–102.
16.Azuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 2014;25:1935–1940.
17.Zhang N, Zeng Y, Du W, et al. The EGFR pathway is involved in the regulation of PD-L1 expression via the IL–6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer. Int J Oncol. 2016;49:1360–1368.
18.Lin K, Cheng J, Yang T, Li Y, Zhu B. EGFR-TKI down-regulates PD-L1 in EGFR mutant NSCLC through inhibiting NF-kappaB. Biochem Biophys Res Commun. 2015;463:95–101.
19.Chen N, Fang W, Zhan J, et al. Upregulation of PD-L1 by EGFR Activation Mediates the Immune Escape in EGFR-Driven NSCLC: Implication for Optional Immune Targeted Therapy for NSCLC Patients with EGFR Mutation. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer. 2015;10:910–923.
20.Han JJ, Kim DW, Koh J, et al. Change in PD-L1 Expression After Acquiring Resistance to Gefitinib in EGFR-Mutant Non-Small-Cell Lung Cancer. Clinical lung cancer. 2016;17:263–270 e262.
21.Soo RA, Lim SM, Syn NL, et al. Immune checkpoint inhibitors in epidermal growth factor receptor mutant non-small cell lung cancer: Current controversies and future directions. Lung cancer. 2018;115:12–20.
22.Ribas A. Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer discovery. 2015;5:915–919.
23.Dong ZY, Zhang JT, Liu SY, et al. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD–1 blockade in non-small cell lung cancer. Oncoimmunology. 2017;6:e1356145.
24.Tomonaga N, Nakamura Y, Yamaguchi H, et al. Analysis of intratumor heterogeneity of EGFR mutations in mixed type lung adenocarcinoma. Clinical lung cancer. 2013;14:521–526.
25.Govindan R, Ding L, Griffith M, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell. 2012;150:1121–1134.
26.Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clinical cancer research: an official journal of the American Association for Cancer Research. 2013;19:2240–2247.
27.Langer CJ. Epidermal growth factor receptor inhibition in mutation-positive non-small-cell lung cancer: is afatinib better or simply newer? Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2013;31:3303–3306.
28.Bourzac K. Biology: Three known unknowns. Nature. 2014;509:S69–71.
29.Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481:306–313.
30.Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nature reviews. Cancer. 2012;12:323–334.