Skip to main content
SpringerLink
Log in

Molecular Pathology of Lung Cancer

  • Chapter
  • First Online:
Lung Cancer

Part of the book series: Current Clinical Oncology ((CCO))

Abstract

In contrast to most other organs, the lungs demonstrate a very wide range of epithelial tumors that vary in their location and histology. These tumors show varying degrees of relationship to smoke exposure, with the central carcinomas showing the greatest relationship. The molecular lesions found in the tumors share certain common elements and have characteristic changes. Their precursor lesions also differ, with some being well defined, whereas others are poorly understood because of the difficulty in identifying them before surgical resection of an existing tumor. Thus, their natural history is also poorly understood. The advent of newer molecular genetic methods to examine lung tumor and preneoplastic lesion tissue specimens will help delineate all the significant molecular abnormalities responsible for lung cancer development and progression. Gene-specific and copy-number alteration approaches have identified mutations that have proven to be unique in lung cancer. Simultaneously, molecular profiling studies at DNA, RNA, and protein levels have provided a molecular classification of lung cancer while also improving the ability to predict prognosis and response to treatment. The integration of these different platforms might overcome the overtraining and instability of the identified signatures. Combining clinical covariates with molecular profiling approaches may be the optimal approach for building new models for lung cancer. The ultimate goal is to be able to identify all molecular changes present in any one patient’s tumor and to use this information for early molecular detection, prediction of biological/clinical behavior and prognosis, and selection or rational development of therapeutics.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Institutional subscriptions

References

  1. Minna JD, Gazdar A (2002) Focus on lung cancer. Cancer Cell 1:49-52

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (2004) Tumours of the lung. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (eds) Pathology and genetics: tumours of the lung, pleura, thymus and heart. International Agency for Research on Cancer (IARC), Lyon, pp 9-124

    Google Scholar 

  4. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70

    Article  PubMed  CAS  Google Scholar 

  5. Fong KM, Sekido Y, Gazdar AF, Minna JD (2003) Lung cancer. 9: molecular biology of lung cancer: clinical implications. Thorax 58:892-900

    Article  PubMed  CAS  Google Scholar 

  6. Herbst RS, Sandler AB (2004) Overview of the current status of human epidermal growth factor receptor inhibitors in lung cancer. Clin Lung Cancer 6(Suppl 1):S7-S19

    Article  PubMed  CAS  Google Scholar 

  7. Herbst RS, Onn A, Sandler A (2005) Angiogenesis and lung cancer: prognostic and therapeutic implications. J Clin Oncol 23:3243-3256

    Article  PubMed  CAS  Google Scholar 

  8. Wistuba II, Mao L, Gazdar AF (2002) Smoking molecular damage in bronchial epithelium. Oncogene 21:7298-7306

    Article  PubMed  CAS  Google Scholar 

  9. Wistuba II (2007) Genetics of preneoplasia: lessons from lung cancer. Curr Mol Med 7:3-14

    Article  PubMed  CAS  Google Scholar 

  10. Westra WH (2000) Early glandular neoplasia of the lung. Respir Med 1:163-169

    CAS  Google Scholar 

  11. Fong KM, Minna JD (2002) Molecular biology of lung cancer: clinical implications. Clin Chest Med 23:83-101

    Article  PubMed  Google Scholar 

  12. Knudson AG (1989) Hereditary cancers: clues to mechanisms of carcinogenesis. Br J Cancer 59:661-666

    Article  PubMed  Google Scholar 

  13. Soda M, Choi YL, Enomoto M et al (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448:561-566

    Article  PubMed  CAS  Google Scholar 

  14. Inamura K, Takeuchi K, Togashi Y et al (2008) EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol 3:13-17

    Article  PubMed  Google Scholar 

  15. Wistuba II, Behrens C, Virmani AK et al (2000) High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res 60:1949-1960

    PubMed  CAS  Google Scholar 

  16. Toyooka S, Toyooka KO, Maruyama R et al (2001) DNA methylation profiles of lung tumors. Mol Cancer Ther 1:61-67

    PubMed  CAS  Google Scholar 

  17. Wistuba II, Gazdar AF, Minna JD (2001) Molecular genetics of small cell lung carcinoma. Semin Oncol 28:3-13

    Article  PubMed  CAS  Google Scholar 

  18. Bhattacharjee A, Richards WG, Staunton J et al (2001) Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 98:13790-13795

    Article  PubMed  CAS  Google Scholar 

  19. Garber ME, Troyanskaya OG, Schluens K et al (2001) Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 98:13784-13789

    Article  PubMed  CAS  Google Scholar 

  20. Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y (2001) The new World Health Organization classification of lung tumours. Eur Respir J 18:1059-1068

    Article  PubMed  CAS  Google Scholar 

  21. Travis WD, Garg K, Franklin WA et al (2005) Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma. J Clin Oncol 23:3279-3287

    Article  PubMed  Google Scholar 

  22. Hammar SP, Brambilla C, Pugatch B et al (2004) Tumours of the lung. Squamous cell carcinoma. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (eds) Pathology and genetics: tumours of the lung, pleura, thymus and heart. IARC, Lyon, pp 26-34

    Google Scholar 

  23. Colby TV, Koss MN, Travis WD (1995) Tumors of the lower respiratory tract, 3rd. series, Fascicle 13. Armed Forces Institute of Pathology, Washington, DC

    Google Scholar 

  24. Brambilla C, Pugatch B, Geisinger K et al (2004) Tumours of the lung. Large cell carcinoma. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (eds) Pathology and genetics: tumours of the lung, pleura, thymus and heart. IARC, Lyon, pp 45-50

    Google Scholar 

  25. Shigematsu H, Lin L, Takahashi T et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 97:339-346

    Article  PubMed  CAS  Google Scholar 

  26. Shigematsu H, Takahashi T, Nomura M et al (2005) Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 65:1642-1646

    Article  PubMed  CAS  Google Scholar 

  27. Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949-954

    Article  PubMed  CAS  Google Scholar 

  28. Brose MS, Volpe P, Feldman M et al (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62:6997-7000

    PubMed  CAS  Google Scholar 

  29. Riely GJ, Kris MG, Rosenbaum D et al (2008) Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res 14:5731-5734

    Article  PubMed  CAS  Google Scholar 

  30. Slebos RJ, Rodenhuis S (1992) The ras gene family in human non-small-cell lung cancer. Monogr Natl Cancer Inst 13:23-29

    PubMed  Google Scholar 

  31. Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497-1500

    Article  PubMed  CAS  Google Scholar 

  32. Lynch TJ, Bell DW, Sordella R 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 350:2129-2139

    Article  PubMed  CAS  Google Scholar 

  33. Pao W, Miller V, Zakowski M 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 USA 101:13306-13311

    Article  PubMed  CAS  Google Scholar 

  34. Huang SF, Liu HP, Li LH et al (2004) High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res 10:8195-8203

    Article  PubMed  CAS  Google Scholar 

  35. Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T (2004) Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res 64:8919-8923

    Article  PubMed  CAS  Google Scholar 

  36. Tokumo M, Toyooka S, Kiura K et al (2005) The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res 11:1167-1173

    PubMed  CAS  Google Scholar 

  37. Amann J, Kalyankrishna S, Massion PP et al (2005) Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer. Cancer Res 65:226-235

    PubMed  CAS  Google Scholar 

  38. Gazdar AF, Shigematsu H, Herz J, Minna JD (2004) Mutations and addiction to EGFR: the Achilles ‘heal’ of lung cancers? Trends Mol Med 10:481-486

    Article  PubMed  CAS  Google Scholar 

  39. Hirsch FR, Varella-Garcia M, Bunn PA Jr et al (2003) Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 21:3798-3807

    Article  PubMed  CAS  Google Scholar 

  40. Cappuzzo F, Hirsch FR, Rossi E et al (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 97:643-655

    Article  PubMed  CAS  Google Scholar 

  41. Tsao MS, Sakurada A, Cutz JC et al (2005) Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 353:133-144

    Article  PubMed  CAS  Google Scholar 

  42. Hirsch FR, Varella-Garcia M, McCoy J et al (2005) Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. J Clin Oncol 23(28):6838-6845

    Article  PubMed  CAS  Google Scholar 

  43. Jackman DM, Holmes AJ, Lindeman N et al (2006) Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib. J Clin Oncol 24:4517-4520

    Article  PubMed  Google Scholar 

  44. Massarelli E, Varella-Garcia M, Tang X 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 13:2890-2896

    Article  PubMed  CAS  Google Scholar 

  45. Bunn PA Jr, Dziadziuszko R, Varella-Garcia M et al (2006) Biological markers for non-small cell lung cancer patient selection for epidermal growth factor receptor tyrosine kinase inhibitor therapy. Clin Cancer Res 12:3652-3656

    Article  PubMed  CAS  Google Scholar 

  46. Zhu CQ, da Cunha Santos G, Ding K et al (2008) Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 26:4268-4275

    Article  PubMed  CAS  Google Scholar 

  47. Pao W, Miller VA, Politi KA et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2:1-11

    Article  CAS  Google Scholar 

  48. Kobayashi S, Boggon TJ, Dayaram T et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352:786-792

    Article  PubMed  CAS  Google Scholar 

  49. Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316:1039-1043

    Article  PubMed  CAS  Google Scholar 

  50. Morgillo F, Kim WY, Kim ES, Ciardiello F, Hong WK, Lee HY (2007) Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res 13:2795-2803

    Article  PubMed  CAS  Google Scholar 

  51. Yauch RL, Januario T, Eberhard DA et al (2005) Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin Cancer Res 11:8686-8698

    Article  PubMed  CAS  Google Scholar 

  52. Weir BA, Woo MS, Getz G et al (2007) Characterizing the cancer genome in lung adenocarcinoma. Nature 450:893-898

    Article  PubMed  CAS  Google Scholar 

  53. Ikeda K, Clark JC, Shaw-White JR, Stahlman MT, Boutell CJ, Whitsett JA (1995) Gene structure and expression of human thyroid transcription factor-1 in respiratory epithelial cells. J Biol Chem 270:8108-8114

    Article  PubMed  CAS  Google Scholar 

  54. Yatabe Y, Kosaka T, Takahashi T, Mitsudomi T (2005) EGFR mutation is specific for terminal respiratory unit type adenocarcinoma. Am J Surg Pathol 29:633-639

    Article  PubMed  Google Scholar 

  55. Perner S, Wagner P, Soltermann A et al (2009) TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival. J Pathol 217:65-72

    Article  PubMed  CAS  Google Scholar 

  56. Ding L, Getz G, Wheeler DA et al (2008) Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455:1069-1075

    Article  PubMed  CAS  Google Scholar 

  57. Toyooka S, Tsuda T, Gazdar AF (2003) The TP53 gene, tobacco exposure, and lung cancer. Hum Mutat 21:229-239

    Article  PubMed  CAS  Google Scholar 

  58. Toyooka S, Maruyama R, Toyooka KO et al (2003) Smoke exposure, histologic type and geography-related differences in the methylation profiles of non-small cell lung cancer. Int J Cancer 103:153-160

    Article  PubMed  CAS  Google Scholar 

  59. Toyooka S, Suzuki M, Maruyama R et al (2004) The relationship between aberrant methylation and survival in non-small-cell lung cancers. Br J Cancer 91:771-774

    PubMed  CAS  Google Scholar 

  60. Ji H, Ramsey MR, Hayes DN et al (2007) LKB1 modulates lung cancer differentiation and metastasis. Nature 448:807-810

    Article  PubMed  CAS  Google Scholar 

  61. Sandler AB, Johnson DH, Herbst RS (2004) Anti-vascular endothelial growth factor monoclonals in non-small cell lung cancer. Clin Cancer Res 10:4258s-4262s

    Article  PubMed  CAS  Google Scholar 

  62. Asahara T, Takahashi T, Masuda H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964-3972

    Article  PubMed  CAS  Google Scholar 

  63. Han H, Silverman JF, Santucci TS et al (2001) Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Ann Surg Oncol 8:72-79

    Article  PubMed  CAS  Google Scholar 

  64. Shikada Y, Yonemitsu Y, Koga T et al (2005) Platelet-derived growth factor-AA is an essential and autocrine regulator of vascular endothelial growth factor expression in non-small cell lung carcinomas. Cancer Res 65:7241-7248

    Article  PubMed  CAS  Google Scholar 

  65. Kim SJ, Rabbani ZN, Dewhirst MW et al (2005) Expression of HIF-1alpha, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer 49:325-335

    Article  PubMed  Google Scholar 

  66. Kuhn H, Kopff C, Konrad J, Riedel A, Gessner C, Wirtz H (2004) Influence of basic fibroblast growth factor on the proliferation of non-small cell lung cancer cell lines. Lung Cancer 44:167-174

    Article  PubMed  Google Scholar 

  67. Dailey L, Ambrosetti D, Mansukhani A, Basilico C (2005) Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev 16:233-247

    Article  PubMed  CAS  Google Scholar 

  68. Ribatti D, Vacca A, Rusnati M, Presta M (2007) The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and its role in haematological malignancies. Cytokine Growth Factor Rev 18(3-4):327-334

    Article  PubMed  CAS  Google Scholar 

  69. Mohammadi M, Olsen SK, Ibrahimi OA (2005) Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev 16:107-137

    Article  PubMed  CAS  Google Scholar 

  70. Takanami I, Tanaka F, Hashizume T et al (1996) The basic fibroblast growth factor and its receptor in pulmonary adenocarcinomas: an investigation of their expression as prognostic markers. Eur J Cancer 32A:1504-1509

    Article  PubMed  CAS  Google Scholar 

  71. Takanami I, Tanaka F, Hashizume T, Kodaira S (1997) Tumor angiogenesis in pulmonary adenocarcinomas: relationship with basic fibroblast growth factor, its receptor, and survival. Neoplasma 44:295-298

    PubMed  CAS  Google Scholar 

  72. Volm M, Koomagi R, Mattern J, Stammler G (1997) Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas. Eur J Cancer 33:691-693

    Article  PubMed  CAS  Google Scholar 

  73. Guddo F, Fontanini G, Reina C, Vignola AM, Angeletti A, Bonsignore G (1999) The expression of basic fibroblast growth factor (bFGF) in tumor-associated stromal cells and vessels is inversely correlated with non-small cell lung cancer progression. Hum Pathol 30:788-794

    Article  PubMed  CAS  Google Scholar 

  74. Shou Y, Hirano T, Gong Y et al (2001) Influence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small-cell lung cancer. Br J Cancer 85:1706-1712

    Article  PubMed  CAS  Google Scholar 

  75. Iwasaki A, Kuwahara M, Yoshinaga Y, Shirakusa T (2004) Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC. Eur J Cardiothorac Surg 25:443-448

    Article  PubMed  Google Scholar 

  76. Bremnes RM, Camps C, Sirera R (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51:143-158

    Article  PubMed  Google Scholar 

  77. Berger W, Setinek U, Mohr T et al (1999) Evidence for a role of FGF-2 and FGF receptors in the proliferation of non-small cell lung cancer cells. Int J Cancer 83:415-423

    Article  PubMed  CAS  Google Scholar 

  78. Behrens C, Lin HY, Lee JJ et al (2008) Immunohistochemical expression of basic fibroblast growth factor and fibroblast growth factor receptors 1 and 2 in the pathogenesis of lung cancer. Clin Cancer Res 14:6014-6022

    Article  PubMed  CAS  Google Scholar 

  79. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442-454

    Article  PubMed  CAS  Google Scholar 

  80. Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7:131-142

    Article  PubMed  CAS  Google Scholar 

  81. Thomson S, Buck E, Petti F et al (2005) Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 65:9455-9462

    Article  PubMed  CAS  Google Scholar 

  82. Elayadi AN, Samli KN, Prudkin L et al (2007) A Peptide Selected by Biopanning Identifies the Integrin {alpha}v{beta}6 as a Prognostic Biomarker for Nonsmall Cell Lung Cancer. Cancer Res 67:5889-5895

    Article  PubMed  CAS  Google Scholar 

  83. Bremnes RM, Veve R, Hirsch FR, Franklin WA (2002) The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis. Lung Cancer 36:115-124

    Article  PubMed  Google Scholar 

  84. Schiller JH, Harrington D, Belani CP et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92-98

    Article  PubMed  CAS  Google Scholar 

  85. Altaha R, Liang X, Yu JJ, Reed E (2004) Excision repair cross complementing-group 1: gene expression and platinum resistance. Int J Mol Med 14:959-970

    PubMed  CAS  Google Scholar 

  86. Simon GR, Sharma S, Cantor A, Smith P, Bepler G (2005) ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. Chest 127:978-983

    Article  PubMed  Google Scholar 

  87. Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G (2007) DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 356:800-808

    Article  PubMed  CAS  Google Scholar 

  88. Lord RV, Brabender J, Gandara D et al (2002) Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res 8:2286-2291

    PubMed  CAS  Google Scholar 

  89. Cobo M, Isla D, Massuti B et al (2007) Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol 25:2747-2754

    Article  PubMed  CAS  Google Scholar 

  90. Olaussen KA, Mountzios G, Soria JC (2007) ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung cancer. Curr Opin Pulm Med 13:284-289

    Article  PubMed  CAS  Google Scholar 

  91. Bepler G, Garcia-Blanco MA (1994) Three tumor-suppressor regions on chromosome 11p identified by high-resolution deletion mapping in human non-small-cell lung cancer. Proc Natl Acad Sci USA 91:5513-5517

    Article  PubMed  CAS  Google Scholar 

  92. Bepler G, Sharma S, Cantor A et al (2004) RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol 22:1878-1885

    Article  PubMed  CAS  Google Scholar 

  93. Bepler G, Kusmartseva I, Sharma S et al (2006) RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol 24:4731-4737

    Article  PubMed  CAS  Google Scholar 

  94. Bepler G (2007) Phase II pharmacogenomics-based adjuvant therapy trial in patients with non-small-cell lung cancer: Southwest Oncology Group Trial 0720. Clin Lung Cancer 8:509-511

    PubMed  Google Scholar 

  95. Travis WD, Nicholson S, Hirsch F et al (2004) Tumours of the lung. Small cell carcinoma. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (eds) Pathology and genetics: tumours of the lung, pleura, thymus and heart. IARC, Lyon, pp 31-34

    Google Scholar 

  96. Wistuba II, Gazdar AF (2000) Molecular pathology of lung cancer. Verh Dtsch Ges Pathol 84:96-105

    PubMed  CAS  Google Scholar 

  97. Girard L, Zochbauer-Muller S, Virmani AK, Gazdar AF, Minna JD (2000) Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res 60:4894-4906

    PubMed  CAS  Google Scholar 

  98. Beer DG, Kardia SL, Huang CC et al (2002) Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med 8:816-824

    PubMed  CAS  Google Scholar 

  99. Larsen JE, Pavey SJ, Passmore LH, Bowman RV, Hayward NK, Fong KM (2007) Gene expression signature predicts recurrence in lung adenocarcinoma. Clin Cancer Res 13:2946-2954

    Article  PubMed  CAS  Google Scholar 

  100. Potti A, Mukherjee S, Petersen R et al (2006) A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 355:570-580

    Article  PubMed  CAS  Google Scholar 

  101. Chen HY, Yu SL, Chen CH et al (2007) A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 356:11-20

    Article  PubMed  CAS  Google Scholar 

  102. Oshita F, Sekiyama A, Saito H, Yamada K, Noda K, Miyagi Y (2006) Genome-wide cDNA microarray screening of genes related to the benefits of paclitaxel and irinotecan chemotherapy in patients with advanced non-small cell lung cancer. J Exp Ther Oncol 6:49-53

    PubMed  CAS  Google Scholar 

  103. Potti A, Dressman HK, Bild A et al (2006) Genomic signatures to guide the use of chemotherapeutics. Nat Med 12:1294-1300

    Article  PubMed  CAS  Google Scholar 

  104. Zohrabian VM, Nandu H, Gulati N et al (2007) Gene expression profiling of metastatic brain cancer. Oncol Rep 18:321-328

    PubMed  CAS  Google Scholar 

  105. Kikuchi T, Daigo Y, Ishikawa N et al (2006) Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray. Int J Oncol 28:799-805

    PubMed  CAS  Google Scholar 

  106. Shedden K, Taylor JM, Enkemann SA et al (2008) Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med 14:822-827

    Article  PubMed  CAS  Google Scholar 

  107. Jay C, Nemunaitis J, Chen P, Fulgham P, Tong AW (2007) miRNA profiling for diagnosis and prognosis of human cancer. DNA Cell Biol 26:293-300

    Article  PubMed  CAS  Google Scholar 

  108. Fabbri M, Croce CM, Calin GA (2008) MicroRNAs. Cancer J 14:1-6

    Article  PubMed  CAS  Google Scholar 

  109. Yanaihara N, Caplen N, Bowman E et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189-198

    Article  PubMed  CAS  Google Scholar 

  110. Volinia S, Calin GA, Liu CG et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103:2257-2261

    Article  PubMed  CAS  Google Scholar 

  111. Yu SL, Chen HY, Chang GC et al (2008) MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 13:48-57

    Article  PubMed  CAS  Google Scholar 

  112. Weiss GJ, Bemis LT, Nakajima E et al (2008) EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann Oncol 19:1053-1059

    Article  PubMed  CAS  Google Scholar 

  113. Wistuba II, Behrens C, Virmani AK et al (1999) Allelic losses at chromosome 8p21-23 are early and frequent events in the pathogenesis of lung cancer. Cancer Res 59:1973-1979

    PubMed  CAS  Google Scholar 

  114. Jiang F, Yin Z, Caraway NP, Li R, Katz RL (2004) Genomic profiles in stage I primary non small cell lung cancer using comparative genomic hybridization analysis of cDNA microarrays. Neoplasia 6:623-635

    Article  PubMed  CAS  Google Scholar 

  115. Garnis C, Lockwood WW, Vucic E et al (2006) High resolution analysis of non-small cell lung cancer cell lines by whole genome tiling path array CGH. Int J Cancer 118:1556-1564

    Article  PubMed  CAS  Google Scholar 

  116. Callinan PA, Feinberg AP (2006) The emerging science of epigenomics. Hum Mol Genet 15 Spec No 1:R95-R101

    Article  PubMed  CAS  Google Scholar 

  117. Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042-2054

    Article  PubMed  CAS  Google Scholar 

  118. Iacobuzio-Donahue CA (2009) Epigenetic changes in cancer. Annu Rev Pathol 4:229-249

    Article  PubMed  CAS  Google Scholar 

  119. Shames DS, Girard L, Gao B et al (2006) A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med 3:e486

    Article  PubMed  CAS  Google Scholar 

  120. Tsou JA, Galler JS, Siegmund KD et al (2007) Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol Cancer 6:70

    Article  PubMed  CAS  Google Scholar 

  121. Yanagawa N, Tamura G, Oizumi H et al (2007) Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers. Lung Cancer 58:131-138

    Article  PubMed  Google Scholar 

  122. Brock MV, Hooker CM, Ota-Machida E et al (2008) DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 358:1118-1128

    Article  PubMed  CAS  Google Scholar 

  123. Wilkins-Haug L (1993) The emerging genetic theories of unstable DNA, uniparental disomy, and imprinting. Curr Opin Obstet Gynecol 5:179-185

    Article  PubMed  CAS  Google Scholar 

  124. Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69:4751-4760

    Article  PubMed  CAS  Google Scholar 

  125. Yanagisawa K, Shyr Y, Xu BJ et al (2003) Proteomic patterns of tumour subsets in non-small-cell lung cancer. Lancet 362:433-439

    Article  PubMed  CAS  Google Scholar 

  126. Taguchi F, Solomon B, Gregorc V et al (2007) Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohort cross-institutional study. J Natl Cancer Inst 99:838-846

    Article  PubMed  CAS  Google Scholar 

  127. Bianchi F, Nicassio F, Di Fiore PP (2008) Unbiased vs. biased approaches to the identification of cancer signatures: the case of lung cancer. Cell Cycle 7:729-734

    Article  PubMed  CAS  Google Scholar 

  128. Colby TV, Wistuba II, Gazdar A (1998) Precursors to pulmonary neoplasia. Adv Anat Pathol 5:205-215

    Article  PubMed  CAS  Google Scholar 

  129. Kerr KM (2001) Pulmonary preinvasive neoplasia. J Clin Pathol 54:257-271

    Article  PubMed  CAS  Google Scholar 

  130. Wistuba II, Behrens C, Milchgrub S et al (1999) Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene 18:643-650

    Article  PubMed  CAS  Google Scholar 

  131. Belinsky SA, Nikula KJ, Palmisano WA et al (1998) Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA 95:11891-11896

    Article  PubMed  CAS  Google Scholar 

  132. Wistuba II, Lam S, Behrens C et al (1997) Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 89:1366-1373

    Article  PubMed  CAS  Google Scholar 

  133. Mao L, Lee JS, Kurie JM et al (1997) Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst 89:857-862

    Article  PubMed  CAS  Google Scholar 

  134. Park IW, Wistuba II, Maitra A et al (1999) Multiple clonal abnormalities in the bronchial epithelium of patients with lung cancer. J Natl Cancer Inst 91:1863-1868

    Article  PubMed  CAS  Google Scholar 

  135. Wistuba II (2005) Histologic evaluation of bronchial squamous lesions: any role in lung cancer risk assessment? Clin Cancer Res 11:1358-1360

    Article  PubMed  CAS  Google Scholar 

  136. Kitamura H, Kameda Y, Ito T, Hayashi H (1999) Atypical adenomatous hyperplasia of the lung. Implications for the pathogenesis of peripheral lung adenocarcinoma [see comments]. Am J Clin Pathol 111:610-622

    PubMed  CAS  Google Scholar 

  137. Osanai M, Igarashi T, Yoshida Y (2001) Unique cellular features in atypical adenomatous hyperplasia of the lung: ultrastructural evidence of its cytodifferentiation. Ultrastruct Pathol 25:367-373

    Article  PubMed  CAS  Google Scholar 

  138. Westra WH, Baas IO, Hruban RH et al (1996) K-ras oncogene activation in atypical alveolar hyperplasias of the human lung. Cancer Res 56:2224-2228

    PubMed  CAS  Google Scholar 

  139. Tominaga M, Sueoka N, Irie K et al (2003) Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hmRNP B1, combined with the cell cycle-related markers p16, cyclin D1, and Ki-67. Lung Cancer 40:45-53

    Article  PubMed  Google Scholar 

  140. Nakanishi K, Kawai T, Kumaki F, Hiroi S, Mukai M, Ikeda E (2003) Survivin expression in atypical adenomatous hyperplasia of the lung. Am J Clin Pathol 120:712-719

    Article  PubMed  Google Scholar 

  141. Tang X, Shigematsu H, Bekele BN et al (2005) EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res 65:7568-7572

    PubMed  CAS  Google Scholar 

  142. Yoshida Y, Shibata T, Kokubu A et al (2005) Mutations of the epidermal growth factor receptor gene in atypical adenomatous hyperplasia and bronchioloalveolar carcinoma of the lung. Lung Cancer 50(1):1-8

    Article  PubMed  Google Scholar 

  143. Tang X, Varella-Garcia M, Xavier AC et al (2008) EGFR abnormalities in the pathogenesis and progression of lung adenocarcinomas. Cancer Prev Res 1:404-408

    Article  Google Scholar 

  144. Wistuba I, Gazdar A (2006) Lung cancer prenoplasia. Annu Rev Pathol Mech Dis 1:331-348

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Unit 85, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA

    Alejandro Corvalan

Authors
  1. Alejandro Corvalan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ignacio I. Wistuba
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alejandro Corvalan .

Editor information

Editors and Affiliations

  1. M. D. Anderson Cancer Center, University of Texas, Holcombe Blvd. 1515, Houston, 77030, U.S.A.

    David J. Stewart

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Corvalan, A., Wistuba, I.I. (2010). Molecular Pathology of Lung Cancer. In: Stewart, D. (eds) Lung Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-524-8_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-524-8_1

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-523-1

  • Online ISBN: 978-1-60761-524-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation