Diffuse Malignant Mesothelioma: Genetic Pathways and Mechanisms of Oncogenesis of Asbestos and Other Agents That Cause Mesotheliomas

  • Françoise Galateau-Sallé
  • Jean Michel Vignaud
Part of the Molecular Pathology Library book series (MPLB, volume 1)


Malignant mesothelioma (MM) is an aggressive neoplasm caused by exposure to asbestos fibers in 80% of cases.1,2 Although asbestos has been banned in most developed countries, the incidence of mesothelioma is still rising because of the long latency period from the time of exposure to development of the disease (20–40 years). Asbestos fibers interact with the mesothelial cells from which these tumors arise in several different ways and generate reactive oxygen species (see Chapter 44), cytokines, and growth factors secondary to inflammatory responses from the host, resulting in DNA damage. Protooncogenes may be activated, leading to cell proliferation and susceptibility to mutations. Over time, structural alterations and numerical losses and gains to chromosomes occur, producing genomic instability and alteration of the role of tumor suppressor genes. These complex cytogenetic and molecular events in MM development attest to the multistep process from a benign proliferation to a malignant neoplasm.


Mesothelial Cell Malignant Pleural Mesothelioma Malignant Mesothelioma Simian Virus Asbestos Exposure 


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  1. 1.
    Goldberg M, Imbernon E, Rolland P, et al. The French National Mesothelioma Surveillance Program. Occup Environ Med 2006 Feb 9;[Epub ahead of print].Google Scholar
  2. 2.
    Galateau-Salle F, Brambilla E, Cagle PT, et al. Pathology of malignant mesothelioma, an update of the International Mesothelioma Panel. In Galateau-Sallé F, ed. London: Springer Verlag; 2006:1–10.Google Scholar
  3. 3.
    Stanton MF, Layard M, Tegeris A, et al. Relation of particles dimension to carcinogenicity in amphibole asbestoses and fibrous minerals. J Natl Cancer Inst 1981;67:965–975.PubMedGoogle Scholar
  4. 4.
    Dodson RF, Atkinson MA, Levin JL. Asbestos fiber length as related to potential pathogenicity: a critical review. Am J Ind Med 2003;44:291–297.PubMedGoogle Scholar
  5. 5.
    Kamp DW, Graceffa P, Prior WA, Weitzman SA. The role of free radicals in asbestos-induced diseases. Free Radic Biol Med 1992;4:293–315.Google Scholar
  6. 6.
    Jaurand MC. Mechanisms of fiber-induced genotoxicity. Environ Health Perspect 1997;105:1073–1084.PubMedGoogle Scholar
  7. 7.
    Sukla A, Gulumian M, Hei TK, et al. Multiple role of oxidants in the pathogenesis of asbestos-induced diseases. Free Radic Biol Med 2003;34:1117–1129Google Scholar
  8. 8.
    Zanella CL, Posada J, Tritton TR, Mossman BT. Asbestos causes stimulation of the extracellular signal-regulated kinase 1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor. Cancer Res 1996;56:5334–5338.PubMedGoogle Scholar
  9. 9.
    Robledo R, Mossmann D. Cellular and molecular mechanism of asbestos induced fibrosis. J Cell Physiol 1999;180:158–166.PubMedGoogle Scholar
  10. 10.
    Caciotti P, Barbone D, Altomare A, et al. SV40-dependant AKT activity drives mesothelial cell transformation after asbestos exposure. Cancer Res 2005;65:5256–5262.Google Scholar
  11. 11.
    Altomare DA, You H, Xiao GH, et al. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted to inhibit tumor cell growth. Oncogene 2005;24:6080–6089.PubMedGoogle Scholar
  12. 12.
    Yang H, Bochetta M, Kroczynski B, et al. TNF-alpha asbestos-induced cytotoxicity via NF-Kappa B dependant pathway mechanism for asbestos oncogenesis. Proc Natl Acad Sci USA 2006;103:10397–10402.PubMedGoogle Scholar
  13. 13.
    Rosenthal GJ, Simeonova P, Corsini E. Asbestos toxicity: an immunologic perspective. Rev Environ Health 1999;14:11–19.PubMedGoogle Scholar
  14. 14.
    Ciccala C, Pompetti F, Carbone M. SV40 induces mesothelioma in hamsters. Am J Pathol 1993;142:1524–1533.Google Scholar
  15. 15.
    Statement on malignant mesothelioma in the United Kingdom: British Thoracic Society Standards of Care Committee. Thorax 2001;56:250–265.Google Scholar
  16. 16.
    Roggli VL, Oury TD, Sporn TA. Mesothelioma. In Roggli VL, Oury TD, Sporn TA, eds. Asbestos Associated Diseases. New York: Springer-Verlag; 2003:109–110.Google Scholar
  17. 17.
    Travis LB, Fossa SD, Schonfeld SJ, et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 2005;97:1354–1365.PubMedGoogle Scholar
  18. 18.
    Allan JM, Travis LB. Mechanisms of therapy-related carcinogenesis. Nat Rev Cancer 2005;5:943–955.PubMedGoogle Scholar
  19. 19.
    Sandberg AA, Bridges J. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Mesothelioma. Cancer Genet Cytogenet 2001;127:93–110.PubMedGoogle Scholar
  20. 20.
    Sandberg AA, Bridge JA. The Cytogenetics of Bone and Soft Tissue Tumors. Austin: RG Landes; 1994.Google Scholar
  21. 21.
    Taguchi T, Jhanwar SC, Siegfried JM, et al. Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res 1993;53:4349–4355.PubMedGoogle Scholar
  22. 22.
    Lee WC, Testa JR. Somatic genetic alterations in human malignant mesothelioma [review]. Int J Oncol 1999;14:181–188.PubMedGoogle Scholar
  23. 23.
    Popescu NC, Chahinian AP, DiPaolo JA. Nonrandom chromosome alterations in human malignant mesothelioma. Cancer Res 1988;48:142–147.PubMedGoogle Scholar
  24. 24.
    Ribotta M, Rosco F, Salvio M, et al. Recurrent chromosome 6 abnormalities in malignant mesothelioma. Monaldi Arch Chest Dis 1998;53:228–235.PubMedGoogle Scholar
  25. 25.
    Segers K, Ramael M, Singh SK, et al. Detection of numerical chromosomal aberrations in paraffin embedded malignant pleural mesothelioma by non-isotopic in situ hybridization. J Pathol 1995;175:219–226.PubMedGoogle Scholar
  26. 26.
    Murthy S, Testa JR. Asbestos, chromosomal deletions and tumor suppressor gene alterations in human malignant mesothelioma. J Cell Physiol 1999;199:150–157.Google Scholar
  27. 27.
    Björkqvist AM, Tammilehto L, Anttila S, et al. Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma. Br J Cancer 1997;75:523–527.PubMedGoogle Scholar
  28. 28.
    Balsara BR, Bell DW, Sonoda G, et al. Comparative genomic hybridization and loss of heterozygosity analyses identify a common region of deletion at 15q11.1-15 in human malignant mesothelioma. Cancer Res 1999;59:450–454.PubMedGoogle Scholar
  29. 29.
    Tiainen M, Tammilehto L, Rautonen JK, et al. Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma. Br J Cancer 1989;60:618–626.PubMedGoogle Scholar
  30. 30.
    Shivapurkar N, Virmani AK, Wistuba II, et al. Deletions of chromosome 4 at multiple sites are frequent in malignant mesothelioma and small cell lung carcinoma. Clin Cancer Res 1999;5:17–23.PubMedGoogle Scholar
  31. 31.
    Bell DW, Jhanwar SC, Testa JR. Multiple regions of allelic loss from chromosome arm 6q in malignant mesothelioma. Cancer Res 1997;57:4057–4062.PubMedGoogle Scholar
  32. 32.
    Negrini M, Sabbioni S, Possati L, et al. Suppression of tumorigenicity of breast cancer cells by microcell-mediated chromosome transfer: studies on chromosomes 6 and 11. Cancer Res 1994;54:1331–1336.PubMedGoogle Scholar
  33. 33.
    Cheng JQ, Lee WC, Klein MA, et al. Frequent mutations of NF2 and allelic loss from chromosome 22q12 in malignant mesothelioma: evidence for a two-hit inactivation. Genes Chromosome Cancer 1999;24:238–242.Google Scholar
  34. 34.
    De Rienzo A, Jhanwar SC, Testa JR. Loss of heterozygosity analysis of 13q and 14q in human malignant mesothelioma. Genes Chromosome Cancer 2000;28:337–341.Google Scholar
  35. 35.
    Lim D, Hasty P. A mutation in mouse rad51 results in early an embryonic lethal that is suppressed by a mutation in p53. Mol Cell Biol 1996;16:7133–7143.PubMedGoogle Scholar
  36. 36.
    Mohr S, Keith G, Galateau-Salle F, et al. Cell protection, resistance and invasiveness of two malignant mesotheliomas as assessed by 10k-microarray. Biochim Biophys Acta 2004;1688:43–60.PubMedGoogle Scholar
  37. 37.
    Pass HI, Liu Z, Wali A, et al. Gene expression profiles predict survival and progression of pleural mesothelioma. Clin Cancer Res 2004;10:849–859.PubMedGoogle Scholar
  38. 38.
    Hoang C, D’Cunha J, Kratzke M, et al. Gene expression profiling identifies matriptase overexpression in malignant mesothelioma. Chest 2004;125:1843–1852.PubMedGoogle Scholar
  39. 39.
    Singhal S, Wiewrodt R, Malden LD, et al. Gene expression profiling of malignant mesothelioma. Clin Cancer Res 2003;9:3080–3097.PubMedGoogle Scholar
  40. 40.
    Lopez-Rios F, Chuai S, Flores R, et al. Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. Cancer Res 2006;66:2970–2979.PubMedGoogle Scholar
  41. 41.
    Gordon GJ, Jensen RV, Hsial LL, et al. Using gene expression ratios to predict outcome among patients with mesothelioma. J Natl Cancer Inst 2003;95:598–605.PubMedGoogle Scholar
  42. 42.
    Hicks J. Biologic, cytogenetic, and molecular factors in mesothelial proliferations. Ultrastruct Pathol 2006;30:19–30.PubMedGoogle Scholar
  43. 43.
    Gordon GJ, Jensen RV, Hsial LL, et al. Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma. Cancer Res 2002;62:4963–4967.PubMedGoogle Scholar
  44. 44.
    Hirvonen A, Pelin K, Tammilehto L, et al. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos related human malignant mesothelioma. Cancer Res 1995;55:2981–2983.PubMedGoogle Scholar
  45. 45.
    Neri M, Filiberti R, Taioli E, et al. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat Res 2005;592:36–44.PubMedGoogle Scholar
  46. 46.
    Dianzani I, Gibello L, Biava A, et al. Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma. Mutat Res 2006;599:124–134.PubMedGoogle Scholar
  47. 47.
    Kratzke RA, Otterson GA, Lincoln CE, et al. Immunohistochemical analysis of the p16INK4 cyclin-dependent kinase inhibitor in malignant mesothelioma. J Natl Cancer Inst 1995;87:1870–1875.PubMedGoogle Scholar
  48. 48.
    Wong L, Zhou J, Anderson D, Kratzke RA. Inactivation of p16INK4a expression in malignant mesothelioma by methylation. Lung Cancer 2002;38:131–136.PubMedGoogle Scholar
  49. 49.
    Hirao T, Bueno R, Chen CJ, et al. Alterations of the p16 (INK4) locus in human malignant mesothelial tumors. Carcinogenesis 2002;23:1127–1130.PubMedGoogle Scholar
  50. 50.
    Prins JB, Williamson KA, Kamp MM, et al. The gene for the cyclin-dependent-kinase-4 inhibitor, CDKN2A, is preferentially deleted in malignant mesothelioma. Int J Cancer 1998;75:649–653.PubMedGoogle Scholar
  51. 51.
    Papp T, Schipper H, Pemsel H, et al. Mutational analysis of N-ras, p53, p16INK4a, p14ARF and CDK4 genes in primary malignant mesothelioma. Int J Oncol 2001;18:425–433.PubMedGoogle Scholar
  52. 52.
    Xio S, Li D, Vijg J, et al. Codeletion of p15 and p16 in primary malignant mesothelioma. Oncogene 1995;11:511–515.PubMedGoogle Scholar
  53. 53.
    Frizelle SP, Grim J, Zhou J, et al. Re-expression of p16INK4a in mesothelioma cells results in cell cycle arrest, cell death, tumor suppression and tumor regression. Oncogene 1998;16:3087–3095.PubMedGoogle Scholar
  54. 54.
    Yang CT, You L, Yeh CC, et al. Adenovirus-mediated p14ARF gene transfer in human mesothelioma cells. J Natl Cancer Inst 2000;92:636–641.PubMedGoogle Scholar
  55. 55.
    Metcalf RA, Welsh JA, Bennet WP, et al. p53 and K-ras mutations in human mesothelioma cell lines. Cancer Res 1992;52:2610–2615.PubMedGoogle Scholar
  56. 56.
    Ramael M, Lemmens G, Eerdekens C, et al. Immunoreactivity for p53 protein in malignant mesothelioma and nonneoplastic mesothelium. J Pathol 1992;168:371–375.PubMedGoogle Scholar
  57. 57.
    Kafiri G, Thomas DM, Shepherd NA, et al. p53 expression is common in malignant mesothelioma. Histopathology 1992;21:331–334.PubMedGoogle Scholar
  58. 58.
    Segers K, Backhovens H, Singh SK, et al. Immunoreactivity for p53 and mdm2 and the detection of p53 mutations in human malignant mesothelioma. Virchows Arch 1995;427:431–436.PubMedGoogle Scholar
  59. 59.
    Mor O, Yaron P, Huszar M, et al. Absence of p53 mutations in malignant mesothelioma. Am J Respir Cell Mol Biol 1997;16:9–13.PubMedGoogle Scholar
  60. 60.
    Ungar S, Van De Meeren A, Tammilehto L, et al. High levels of MDM2 are not correlated with the presence of wild-type p53 in human malignant mesothelioma cell lines. Br J Cancer 1996;74:1534–1540.PubMedGoogle Scholar
  61. 61.
    Hopkins-Donaldson S, Belyanskaya LL, Simoes-Wurst AP, et al. p53-induced apoptosis occurs in the absence of p14ARF in malignant pleural mesothelioma. Neoplasia 2006;7:551–559.Google Scholar
  62. 62.
    Carbone M, Rizzo P, Grimley PM, et al. Simian virus 40 large T antigen binds p53 in human mesotheliomas. Nature Med 1999;8:908–912.Google Scholar
  63. 63.
    Baldi A, Groeger AM, Esposito V, et al. Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival. Thorax 2002;57:353–356.PubMedGoogle Scholar
  64. 64.
    Sekido Y, Pass HI, Bader S, et al. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res 1995;55:1227–1231.PubMedGoogle Scholar
  65. 65.
    Bianchi AB, Mitsunaga SI, Cheng JQ, et al. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci USA 1995;92:10854–10858.PubMedGoogle Scholar
  66. 66.
    Poulikakos PI, Xiao GH, Gallagher R, et al. Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK. Oncogene 2006;25:5960–8.PubMedGoogle Scholar
  67. 67.
    Lecomte C, Andujar P, Renier A, et al. Similar tumor suppressor gene alteration profiles in asbestos-induced murine and human mesothelioma. Cell Cycle 2005;12:1862–1869.Google Scholar
  68. 68.
    Altomare DA, Vaslet CA, Skele KL, et al. A mouse model recapitulating molecular features of human mesothelioma. Cancer Res 2005;65:8090–8095.PubMedGoogle Scholar
  69. 69.
    Suzuki M, Toyooka S, Shivapurkar N, et al. Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection. Oncogene 2005;24:1302–1308.PubMedGoogle Scholar
  70. 70.
    Fischer JR, Ohnmacht U, Rieger N, et al. Promoter methylation of RASSF1A, RARβ, and DAPK predict poor prognosis of patients with malignant mesothelioma. Lung Cancer 2006;54(1):109–116.PubMedGoogle Scholar
  71. 71.
    Toyooka S, Pass HI, Shivapurkar N, et al. Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma. Cancer Res 2001;61:5727–5730.PubMedGoogle Scholar
  72. 72.
    Jasani B, Cristaudo A, Emri SA, et al. Association of SV40 with human tumors. Seminar Cancer Biol 2001;11:49–61.Google Scholar
  73. 73.
    Carbone M, Pass HI, Rizzo P, et al. Simian virus 40-like DNA sequences in human pleural mesothelioma. Oncogene 1994;9:1781–1790.PubMedGoogle Scholar
  74. 74.
    Galateau-Salle F, Bidet P, Iwatsubo Y, et al. SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and non-malignant pulmonary diseases. J Pathol 1998;184:252–257.PubMedGoogle Scholar
  75. 75.
    Vilchez RA, Butel JS. Emergent human pathogen simian virus 40 and its role in cancer. Clinical Microbiol Rev 2004;17:495–508.Google Scholar
  76. 76.
    Testa JR, Carbone M, Hirvonen A, et al. A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas. Cancer Res 1998;58:4505–4509.PubMedGoogle Scholar
  77. 77.
    Lednicky JA, Butel JS. Simian virus 40 regulatory region structural diversity and the association of viral archetypal regulatory regions with human brain tumors. Semin Cancer Biol 2001;11:39–47.PubMedGoogle Scholar
  78. 78.
    Carbone M, Kratzke RA, Testa JR. The pathogenesis of mesothelioma. Semin Oncol 2002;29:2–17.PubMedGoogle Scholar
  79. 79.
    Bocchetta M, Di Resta I, Powers A, et al. Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity. Proc Natl Acad Sci USA 2000;97:10214–10219.PubMedGoogle Scholar
  80. 80.
    Burmeister B, Schwerdtle T, Poser I, et al. Effects of asbestos on initiation of DNA damage, induction of DNA-strand breaks, p53 expression and apoptosis in primary SV40-transformed and malignant human mesothelioma cells. Mutation Res 2004;558:81–92.PubMedGoogle Scholar
  81. 81.
    Gazdar AF, Butel JS, Carbone M. SV 40 and human tumours: myth, association or casualty? Nat Rev Cancer 2002;2:957–964.PubMedGoogle Scholar
  82. 82.
    Shivapurkar N, Wiethege T, Wistuba II, et al. Presence of simian virus 40 sequences in malignant mesotheliomas and mesothelial cell proliferations. J Cell Biochem 1999;76:181–188.PubMedGoogle Scholar
  83. 83.
    Saenz-Robles MT, Sullivan CS, Pipas JM. Transforming functions of simian virus 40. Oncogene 2001;20:7899–7907.PubMedGoogle Scholar
  84. 84.
    Khalili K, Stoner G, editors. Human Polyomaviruses: Molecular and Clinical Perspectives. New York: Wiley-Liss; 2001.Google Scholar
  85. 85.
    Sullivan CS, Pipas JL. T antigens of simian virus 40: molecular chaperones for viral replication and tumorigenesis. Microbiol Mol Biol 2002;66:179–202.Google Scholar
  86. 86.
    Foddis R, De Rienzo A, Broccoli D, et al. SV40 infection induces telomerase activity in human mesothelial cells. Oncogene 2002;21:1434–1442.PubMedGoogle Scholar
  87. 87.
    Cacciotti P, Libener R, Betta F, et al. SV40 replication in human mesothelial cells induces HGF/MET receptor activation: a model for viral-related mesothelioma. Proc Natl Acad Sci USA 2001;98:12032–12037.PubMedGoogle Scholar
  88. 88.
    Stratton K, Almario DA, McCormik MC. Immunization Safety Review: SV40 Contamination of Polio Vaccine and Cancer. Washington, DC: The National Academic Press; 2003.Google Scholar
  89. 89.
    King JE, Thatcher N, Pickering CA, Hasleton PS. Sensitivity and specificity of immunohistochemical markers used in the diagnosis of epithelioid mesothelioma: a detailed systematic analysis using published data. Histopathology 2006;48:223–232.PubMedGoogle Scholar
  90. 90.
    Maheswaran S, Englen C, Bennet P, et al. The WT 1 gene product stabilizes p53 and inhibits p53-mediated apoptosis Genes Dev 1995;9:2143–2156.PubMedGoogle Scholar
  91. 91.
    Scharnhorst V, Dekker P, van der Eb AJ, Jochemsen AG. Physical interaction between WT1 and p73 proteins modulates their functions. J Biol Chem 2000;275:10202–10211.PubMedGoogle Scholar
  92. 92.
    Amin KM, Litzky LA, Smythe WR, et al. Wilms’ tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma. Am J Pathol 1995;186:300–305.Google Scholar
  93. 93.
    Uematsu K, Kanazawa S, You L, et al. Wnt pathway activation in mesothelioma: evidence of disheveled overexpression and transcriptional activity of beta-catenin. Cancer Res 2003;63:4547–4551.PubMedGoogle Scholar
  94. 94.
    You L, He B, Uematsu K, et al. Inhibition of wnt-1 signaling induces apoptosis in beta-catenin deficient mesothelioma cells. Cancer Res 2004;64:3474–3478.PubMedGoogle Scholar
  95. 95.
    Chen S, Guttridge DC, You Z, et al. Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T-cell factor-mediated transcription. J Cell Biol 2001;152:87–96.PubMedGoogle Scholar
  96. 96.
    Liu Z, Klominek J. Chemotaxis and chemokinesis of malignant mesothelioma cells to multiple growths factors. Anticancer Res 2004;24(3a):1625–1630.PubMedGoogle Scholar
  97. 97.
    Syrokou A, Tzanakakis GN, Hjerpe A, Karamanos NK. Proteoglycans in human malignant mesothelioma. Stimulation of their synthesis induced by epidermal, insulin and platelet-derived growth factors involves receptor with tyrosine kinase activity. Biochimie 1999;81:733–744.PubMedGoogle Scholar
  98. 98.
    Hoang CD, Zhang X, Scott PD, et al. Selective activation of insulin receptor substrate-1 and-2 in pleural mesothelioma cells: association with distinct malignant phenotypes. Cancer 2004;64:7479–7485.Google Scholar
  99. 99.
    Porcu P, Ferber A, Pietrzkowski Z, et al. The growthstimulatory effect of simian virus 40 T antigen requires the interaction of insulin like growth factor 1 with its receptor. Mol Cell Biol 1992;11:5069–5077.Google Scholar
  100. 100.
    Gerwin BI, Lechner JF, Reddel RR, et al. Comparison of production of transforming growth factor-beta and platelet-derived growth factor by normal human mesothelial cells and mesothelioma cells lines. Cancer Res 1987;47:6180–6184.PubMedGoogle Scholar
  101. 101.
    Versnel MA, Hagemeijer A, Bouts MJ, et al. Expression of c-sis (PDGF B-chain) and PDGF A-chain genes in ten human malignant mesothelioma cell lines derived from primary and metastatic tumors. Oncogene 1988;2:601–605.PubMedGoogle Scholar
  102. 102.
    Jänne PA, Taffaro M, Salgia R, Johson B. Inhibition of epidermal growth factor signaling in malignant pleural mesothelioma. Cancer Res 2002;62:5242–5247.PubMedGoogle Scholar
  103. 103.
    Dazzi H, Hasleton P, Thatcher N, et al. Malignant pleural mesothelioma and epidermal growth factor 5EGF-R). Relashionship of EGF-R with histology and survival using paraffin embedded tissue and the F4 monoclonal antibody. Br J Cancer 1990;61:924–926.PubMedGoogle Scholar
  104. 104.
    Cai Y, Roggli V, Mark E, et al. Transforming growth factor alpha and epidermal growth factor receptor in reactive and malignant mesothelial proliferations. Arch Pathol Lab Med 2004;128:68–70.PubMedGoogle Scholar
  105. 105.
    Govindan R, Kratzke RA, Herndon JE 2nd, et al. Cancer and leukemia group B. Clin Cancer Res 2005;11:2300–2304.PubMedGoogle Scholar
  106. 106.
    Cortese JF, Gowda AL, Wali A, et al. Common EGFR mutations conferring sensitivity to gefitinib in lung adenocarcinoma are not prevalent in human malignant mesothelioma. Int J Cancer 2006;118:521–552.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Françoise Galateau-Sallé
    • 1
  • Jean Michel Vignaud
    • 2
  1. 1.Department of Pathology, INSERM ERI 3CHU CaenCaen, CalvadosFrance
  2. 2.Department of Pathology (Mesopath Group) and INSERM ER3CHU CaenFrance

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