Skip to main content

Diagnosis and Molecular Classification of Lung Cancer

Part of the Cancer Treatment and Research book series (CTAR,volume 170)

Abstract

Lung cancer is a complex disease composed of diverse histological and molecular types with clinical relevance. The advent of large-scale molecular profiling has been helpful to identify novel molecular targets that can be applied to the treatment of particular lung cancer patients and has helped to reshape the pathological classification of lung cancer. Novel directions include the immunotherapy revolution, which has opened the door for new opportunities for cancer therapy and is also redefining the classification of multiple tumors, including lung cancer. In the present chapter, we will review the main current basis of the pathological diagnosis and classification of lung cancer incorporating the histopathological and molecular dimensions of the disease.

Keywords

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. American Cancer Society (2015) Cancer facts & figures 2015. American Cancer Society, Atlanta

    Google Scholar 

  2. Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359(13):1367–1380

    Article  CAS  PubMed  Google Scholar 

  3. Travis WD et al (2013) Diagnosis of lung adenocarcinoma in resected specimens: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 137(5):685–705

    Article  PubMed  Google Scholar 

  4. Travis WD, Brambilla E, Riely GJ (2013) New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol 31(8):992–1001

    Article  CAS  PubMed  Google Scholar 

  5. Fujimoto J, Wistuba II (2014) Current concepts on the molecular pathology of non-small cell lung carcinoma. Semin Diagn Pathol 31(4):306–313

    Google Scholar 

  6. Travis WD, Bambrilla E, Burke AP, Marx A, Nicholson AG (2015) WHO classification of tumours of the lung, pleura, thymus and heart, 4th edn. IARC WHO Classification of Tumours 2015: World Health Organization

    Google Scholar 

  7. Biesalski HK et al (1998) European consensus statement on lung cancer: risk factors and prevention. Lung Cancer Panel. CA Cancer J Clin 48(3):167–76 (discussion 164–166)

    Google Scholar 

  8. Hecht SS (2012) Lung carcinogenesis by tobacco smoke. Int J Cancer 131(12):2724–2732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Khuder SA (2001) Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis. Lung Cancer 31(2–3):139–148

    Article  CAS  PubMed  Google Scholar 

  10. Rosai J (2007) Why microscopy will remain a cornerstone of surgical pathology. Lab Invest 87(5):403–408

    Article  PubMed  Google Scholar 

  11. Kadota K et al (2015) Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis. Am J Surg Pathol 9:1170–1180

    Google Scholar 

  12. Rekhtman N et al (2011) Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol 24(10):1348–1359

    Article  PubMed  Google Scholar 

  13. Travis WD, Rekhtman N (2011) Pathological diagnosis and classification of lung cancer in small biopsies and cytology: strategic management of tissue for molecular testing. Semin Respir Crit Care Med 32(1):22–31

    Article  PubMed  Google Scholar 

  14. Travis WD et al (2011) International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6(2):244–285

    Article  PubMed  PubMed Central  Google Scholar 

  15. Dela Cruz CS, Tanoue LT, Matthay RA (2011) Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med 32(4):605–644

    Google Scholar 

  16. Shimosato Y et al (1980) Prognostic implications of fibrotic focus (scar) in small peripheral lung cancers. Am J Surg Pathol 4(4):365–373

    Article  CAS  PubMed  Google Scholar 

  17. Russell PA et al (2011) Does lung adenocarcinoma subtype predict patient survival? A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol 6(9):1496–1504

    Article  PubMed  Google Scholar 

  18. Russell PA et al (2013) Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ATS/ERS lung adenocarcinoma classification in stage III (N2) patients. J Thorac Oncol 8(4):461–468

    Article  PubMed  Google Scholar 

  19. Voldborg BR et al (1997) Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Oncol 8(12):1197–1206

    Article  CAS  PubMed  Google Scholar 

  20. Lynch TJ et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139

    Article  CAS  PubMed  Google Scholar 

  21. Paez JG et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500

    Article  CAS  PubMed  Google Scholar 

  22. Pao W et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci US A 101(36):13306–13311

    Article  CAS  Google Scholar 

  23. Soh J et al (2009) Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI) frequently occur together in tumor cells. PLoS ONE 4(10):e7464

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Ladanyi M, Pao W (2008) Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Mod Pathol 21(Suppl 2):S16–S22

    Article  CAS  PubMed  Google Scholar 

  25. Sordella R et al (2004) Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305(5687):1163–1167

    Article  CAS  PubMed  Google Scholar 

  26. Morris SW et al (1994) Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 263(5151):1281–1284

    Article  CAS  PubMed  Google Scholar 

  27. Roskoski R Jr (2013) Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition. Pharmacol Res 68(1):68–94

    Article  CAS  PubMed  Google Scholar 

  28. Kwak EL et al (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363(18):1693–1703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shinmura K et al (2008) EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung Cancer 61(2):163–169

    Article  PubMed  Google Scholar 

  30. Wong DW et al (2009) The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 115(8):1723–1733

    Article  CAS  PubMed  Google Scholar 

  31. Choi YL et al (2008) Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res 68(13):4971–4976

    Article  CAS  PubMed  Google Scholar 

  32. Takeuchi K et al (2009) KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 15(9):3143–3149

    Article  CAS  PubMed  Google Scholar 

  33. Horn L, Pao W (2009) EML4-ALK: honing in on a new target in non-small-cell lung cancer. J Clin Oncol 27(26):4232–4235

    Article  CAS  PubMed  Google Scholar 

  34. Koivunen JP et al (2008) EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res 14(13):4275–4283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Soda M et al (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561–566

    Article  CAS  PubMed  Google Scholar 

  36. Shaw AT et al (2009) Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 27(26):4247–4253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mano H (2008) Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer. Cancer Sci 99(12):2349–2355

    Article  CAS  PubMed  Google Scholar 

  38. Rikova K et al (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131(6):1190–1203

    Article  CAS  PubMed  Google Scholar 

  39. Inamura K et al (2009) EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. Mod Pathol 22(4):508–515

    Article  CAS  PubMed  Google Scholar 

  40. Yi ES et al (2011) Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH. J Thorac Oncol 6(3):459–465

    Article  PubMed  Google Scholar 

  41. Bang YJ (2011) The potential for crizotinib in non-small cell lung cancer: a perspective review. Ther Adv Med Oncol 3(6):279–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Choi YL et al (2010) EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med 363(18):1734–1739

    Article  CAS  PubMed  Google Scholar 

  43. Sasaki T et al (2010) The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res 70(24):10038–10043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Popescu NC, King CR, Kraus MH (1989) Localization of the human erbB-2 gene on normal and rearranged chromosomes 17 to bands q12-21.32. Genomics 4(3):362–366

    Article  CAS  PubMed  Google Scholar 

  45. Buttitta F et al (2006) Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer 119(11):2586–2591

    Article  CAS  PubMed  Google Scholar 

  46. Shigematsu H et al (2005) Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 65(5):1642–1646

    Article  CAS  PubMed  Google Scholar 

  47. Stephens P et al (2004) Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431(7008):525–526

    Article  CAS  PubMed  Google Scholar 

  48. Serizawa M et al (2014) Assessment of mutational profile of Japanese lung adenocarcinoma patients by multitarget assays: a prospective, single-institute study. Cancer 120(10):1471–1481

    Article  CAS  PubMed  Google Scholar 

  49. Li C et al (2014) Prognostic value analysis of mutational and clinicopathological factors in non-small cell lung cancer. PLoS ONE 9(9):e107276

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Wang SE et al (2006) HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 10(1):25–38

    Article  PubMed  CAS  Google Scholar 

  51. Bergethon K et al (2012) ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 30(8):863–870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Davies KD et al (2012) Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. Clin Cancer Res 18(17):4570–4579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Takeuchi K et al (2012) RET, ROS1 and ALK fusions in lung cancer. Nat Med 18(3):378–381

    Article  CAS  PubMed  Google Scholar 

  54. Shaw AT et al (2014) Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 371(21):1963–1971

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Knowles PP et al (2006) Structure and chemical inhibition of the RET tyrosine kinase domain. J Biol Chem 281(44):33577–33587

    Article  CAS  PubMed  Google Scholar 

  56. Ju YS et al (2012) A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 22(3):436–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kohno T et al (2012) KIF5B-RET fusions in lung adenocarcinoma. Nat Med 18(3):375–377

    Article  CAS  PubMed  Google Scholar 

  58. Lipson D et al (2012) Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 18(3):382–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wang R et al (2012) RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol 30(35):4352–4359

    Article  CAS  PubMed  Google Scholar 

  60. Drilon A et al (2013) Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov 3(6):630–635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sossin WS (2006) Tracing the evolution and function of the Trk superfamily of receptor tyrosine kinases. Brain Behav Evol 68(3):145–156

    Article  PubMed  Google Scholar 

  62. Nakagawara A (2001) Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett 169(2):107–114

    Article  CAS  PubMed  Google Scholar 

  63. Alberti L et al (2003) RET and NTRK1 proto-oncogenes in human diseases. J Cell Physiol 195(2):168–186

    Article  CAS  PubMed  Google Scholar 

  64. Martin-Zanca D, Hughes SH, Barbacid M (1986) A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 319(6056):743–748

    Article  CAS  PubMed  Google Scholar 

  65. Greco A, Miranda C, Pierotti MA (2010) Rearrangements of NTRK1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol 321(1):44–49

    Article  CAS  PubMed  Google Scholar 

  66. Kim J et al (2014) NTRK1 fusion in glioblastoma multiforme. PLoS ONE 9(3):e91940

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Vaishnavi A et al (2013) Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med 19(11):1469–1472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Doebele RC et al (2015) An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101. Cancer Discov 5(10):1049–1057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Trusolino L, Bertotti A, Comoglio PM (2010) MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 11(12):834–848

    Article  CAS  PubMed  Google Scholar 

  70. Zhen Z et al (1994) Structural and functional domains critical for constitutive activation of the HGF-receptor (Met). Oncogene 9(6):1691–1697

    CAS  PubMed  Google Scholar 

  71. Yi S, Tsao MS (2000) Activation of hepatocyte growth factor-met autocrine loop enhances tumorigenicity in a human lung adenocarcinoma cell line. Neoplasia 2(3):226–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cooper CS et al (1984) Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311(5981):29–33

    Article  CAS  PubMed  Google Scholar 

  73. Kong-Beltran M et al (2006) Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res 66(1):283–289

    Article  CAS  PubMed  Google Scholar 

  74. Ma PC et al (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63(19):6272–6281

    CAS  PubMed  Google Scholar 

  75. Kong-Beltran M, Stamos J, Wickramasinghe D (2004) The sema domain of met is necessary for receptor dimerization and activation. Cancer Cell 6(1):75–84

    Article  CAS  PubMed  Google Scholar 

  76. Ichimura E et al (1996) Expression of c-met/HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn J Cancer Res 87(10):1063–1069

    Article  CAS  PubMed  Google Scholar 

  77. Olivero M et al (1996) Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas. Br J Cancer 74(12):1862–1868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Benedettini E et al (2010) Met activation in non-small cell lung cancer is associated with de novo resistance to EGFR inhibitors and the development of brain metastasis. Am J Pathol 177(1):415–423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nakamura Y et al (2007) c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis. Cancer Sci 98(7):1006–1013

    Article  CAS  PubMed  Google Scholar 

  80. Onozato R et al (2009) Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers. J Thorac Oncol 4(1):5–11

    Article  PubMed  Google Scholar 

  81. Onitsuka T et al (2010) Comprehensive molecular analyses of lung adenocarcinoma with regard to the epidermal growth factor receptor, K-ras, MET, and hepatocyte growth factor status. J Thorac Oncol 5(5):591–596

    Article  PubMed  Google Scholar 

  82. Beau-Faller M et al (2008) MET gene copy number in non-small cell lung cancer: molecular analysis in a targeted tyrosine kinase inhibitor naive cohort. J Thorac Oncol 3(4):331–339

    Article  PubMed  Google Scholar 

  83. Frampton GM et al (2015) Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 5(8):850–859

    Article  CAS  PubMed  Google Scholar 

  84. McBride OW et al (1983) Regional chromosomal localization of N-ras, K-ras-1, K-ras-2 and myb oncogenes in human cells. Nucleic Acids Res 11(23):8221–8236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jancik S et al (2010) Clinical relevance of KRAS in human cancers. J Biomed Biotechnol 2010:150960

    PubMed  PubMed Central  Google Scholar 

  86. Tam IY et al (2006) Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res 12(5):1647–1653

    Article  CAS  PubMed  Google Scholar 

  87. Guerra C et al (2003) Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell 4(2):111–120

    Article  CAS  PubMed  Google Scholar 

  88. Popescu NC et al (1985) Chromosomal localization of three human ras genes by in situ molecular hybridization. Somat Cell Mol Genet 11(2):149–155

    Article  CAS  PubMed  Google Scholar 

  89. Soung YH et al (2005) Mutational analysis of EGFR and K-RAS genes in lung adenocarcinomas. Virchows Arch 446(5):483–488

    Article  CAS  PubMed  Google Scholar 

  90. Riely GJ et al (2008) Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res 14(18):5731–5734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Sun Y et al (2010) Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases. J Clin Oncol 28(30):4616–4620

    Article  PubMed  PubMed Central  Google Scholar 

  92. Pao W et al (2005) KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2(1):e17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Eberhard DA et al (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23(25):5900–5909

    Article  CAS  PubMed  Google Scholar 

  94. Massarelli E et al (2007) KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 13(10):2890–2896

    Article  CAS  PubMed  Google Scholar 

  95. Riely GJ, Ladanyi M (2008) KRAS mutations: an old oncogene becomes a new predictive biomarker. J Mol Diagn 10(6):493–495

    Article  PubMed  PubMed Central  Google Scholar 

  96. Wan PT et al (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116(6):855–867

    Article  CAS  PubMed  Google Scholar 

  97. Brose MS et al (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62(23):6997–7000

    CAS  PubMed  Google Scholar 

  98. Cardarella S et al (2013) Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res 19(16):4532–4540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Davies H et al (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954

    Article  CAS  PubMed  Google Scholar 

  100. Naoki K et al (2002) Missense mutations of the BRAF gene in human lung adenocarcinoma. Cancer Res 62(23):7001–7003

    CAS  PubMed  Google Scholar 

  101. Paik PK et al (2011) Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 29(15):2046–2051

    Article  PubMed  PubMed Central  Google Scholar 

  102. Pratilas CA et al (2008) Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res 68(22):9375–9383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Fang M et al (2014) A comparison of consistency of detecting BRAF gene mutations in peripheral blood and tumor tissue of nonsmall-cell lung cancer patients. J Cancer Res Ther 10(Suppl):C150–C154

    PubMed  Google Scholar 

  104. Gautschi O et al (2012) A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib. J Thorac Oncol 7(10):e23–e24

    Article  PubMed  Google Scholar 

  105. Falchook GS et al (2012) Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 379(9829):1893–1901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gautschi O et al (2015) Targeted therapy for patients with BRAF-mutant lung cancer: results from the European EURAF cohort. J Thorac Oncol 10(10):1451–1457

    Article  CAS  PubMed  Google Scholar 

  107. Hyman DM et al (2015) Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 373(8):726–736

    Article  CAS  PubMed  Google Scholar 

  108. McCormick F (1995) Ras-related proteins in signal transduction and growth control. Mol Reprod Dev 42(4):500–506

    Article  CAS  PubMed  Google Scholar 

  109. Ding L et al (2008) Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455(7216):1069–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Ohashi K et al (2013) Characteristics of lung cancers harboring NRAS mutations. Clin Cancer Res 19(9):2584–2591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Sasaki H et al (2007) Nras and Kras mutation in Japanese lung cancer patients: genotyping analysis using lightcycler. Oncol Rep 18(3):623–628

    CAS  PubMed  Google Scholar 

  112. Reynolds SH et al (1991) Activated protooncogenes in human lung tumors from smokers. Proc Natl Acad Sci USA 88(4):1085–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Huang MH et al (2013) MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib. Mol Oncol 7(1):112–120

    Article  CAS  PubMed  Google Scholar 

  114. Franke TF (2008) PI3K/Akt: getting it right matters. Oncogene 27(50):6473–6488

    Article  CAS  PubMed  Google Scholar 

  115. Bleeker FE et al (2008) AKT1 (E17K) in human solid tumours. Oncogene 27(42):5648–5650

    Article  CAS  PubMed  Google Scholar 

  116. Malanga D et al (2008) Activating E17K mutation in the gene encoding the protein kinase AKT1 in a subset of squamous cell carcinoma of the lung. Cell Cycle 7(5):665–669

    Article  CAS  PubMed  Google Scholar 

  117. Carpten JD et al (2007) A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448(7152):439–444

    Article  CAS  PubMed  Google Scholar 

  118. Derijard B et al (1995) Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267(5198):682–685

    Article  CAS  PubMed  Google Scholar 

  119. Arcila ME et al (2015) MAP2K1 (MEK1) mutations define a distinct subset of lung adenocarcinoma associated with smoking. Clin Cancer Res 21(8):1935–1943

    Article  CAS  PubMed  Google Scholar 

  120. Marks JL et al (2008) Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma. Cancer Res 68(14):5524–5528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Karakas B, Bachman KE, Park BH (2006) Mutation of the PIK3CA oncogene in human cancers. Br J Cancer 94(4):455–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Hiles ID et al (1992) Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit. Cell 70(3):419–429

    Article  CAS  PubMed  Google Scholar 

  123. Samuels Y, Ericson K (2006) Oncogenic PI3K and its role in cancer. Curr Opin Oncol 18(1):77–82

    Article  CAS  PubMed  Google Scholar 

  124. Kawano O et al (2006) PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer 54(2):209–215

    Article  PubMed  Google Scholar 

  125. Lee JW et al (2005) PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 24(8):1477–1480

    Article  CAS  PubMed  Google Scholar 

  126. Oxnard GR, Binder A, Janne PA (2013) New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol 31(8):1097–1104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Sequist LV et al (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3(75):75ra26

    Google Scholar 

  128. Chaft JE et al (2012) Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther 11(2):485–491

    Article  CAS  PubMed  Google Scholar 

  129. Xu J et al (2011) Somatic mutation analysis of EGFR, KRAS, BRAF and PIK3CA in 861 patients with non-small cell lung cancer. Cancer Biomark 10(2):63–69

    CAS  PubMed  Google Scholar 

  130. Anagnostou VK et al (2009) Thyroid transcription factor 1 is an independent prognostic factor for patients with stage I lung adenocarcinoma. J Clin Oncol 27(2):271–278

    Article  PubMed  Google Scholar 

  131. Berghmans T et al (2006) Thyroid transcription factor 1–a new prognostic factor in lung cancer: a meta-analysis. Ann Oncol 17(11):1673–1676

    Article  CAS  PubMed  Google Scholar 

  132. Crum CP, McKeon FD (2010) p63 in epithelial survival, germ cell surveillance, and neoplasia. Annu Rev Pathol 5:349–371

    Article  CAS  PubMed  Google Scholar 

  133. Travis WD et al (2013) Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 137(5):668–684

    Article  PubMed  Google Scholar 

  134. Collins FS, Varmus H (2015) A new initiative on precision medicine. N Engl J Med 372(9):793–795

    Article  CAS  PubMed  Google Scholar 

  135. Topalian SL et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Brahmer JR et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Massarelli E et al (2014) Immunotherapy in lung cancer. Transl Lung Cancer Res 3(1):53–63

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Anagnostou VK, Brahmer JR (2015) Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer. Clin Cancer Res 21(5):976–984

    Article  CAS  PubMed  Google Scholar 

  139. Brahmer JR (2014) Immune checkpoint blockade: the hope for immunotherapy as a treatment of lung cancer? Semin Oncol 41(1):126–132

    Article  CAS  PubMed  Google Scholar 

  140. Velcheti V et al (2014) Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 94(1):107–116

    Article  CAS  PubMed  Google Scholar 

  141. Schalper KA et al (2015) Objective measurement and clinical significance of TILs in non-small cell lung cancer. J Natl Cancer Inst 107(3):dju435

    Google Scholar 

  142. Teng MW et al (2015) Classifying cancers based on T-cell Infiltration and PD-L1. Cancer Res 75(11):2139–2145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Kerr KM et al (2015) Programmed death-ligand 1 immunohistochemistry in lung cancer: in what state is this art? J Thorac Oncol 10(7):985–989

    Article  CAS  PubMed  Google Scholar 

  144. Garon EB et al (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372(21):2018–2028

    Article  PubMed  Google Scholar 

  145. Brahmer J et al (2015) Nivolumab versus Docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Borghaei H et al (2015) Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17):1627–1639

    Article  CAS  PubMed  Google Scholar 

  147. Herbst RS et al (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528):563–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Rizvi NA et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348(6230):124–128

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ignacio I. Wistuba .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Rodriguez-Canales, J., Parra-Cuentas, E., Wistuba, I.I. (2016). Diagnosis and Molecular Classification of Lung Cancer. In: Reckamp, K. (eds) Lung Cancer. Cancer Treatment and Research, vol 170. Springer, Cham. https://doi.org/10.1007/978-3-319-40389-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-40389-2_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-40387-8

  • Online ISBN: 978-3-319-40389-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics