Molekulare Pathologie bösartiger pulmonaler und pleuraler Tumoren

  • Klaus-Michael Müller
  • Thorsten Wiethege
  • Michael Krismann
  • Klaus Junker
  • Georg Johnen
Part of the Molekulare Medizin book series (MOLMED)


Die Therapie und die Prognase bösartiger Tumoren der hängen entscheidend von
  • der Tumorgröße,

  • dem Tumorstadium und

  • der histopatholosgischen Charakterisierung zum Zeitpunkt der Diagnosestellung ab.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abeloff MD, Eggleston JC, Mendelsohn G, Ettinger DS, Baylin SB (1979) Changes in morphologie and biochemical characteristics of small cell carcinoma of the lung. Am J Med 66:757–764PubMedGoogle Scholar
  2. Ahrendt SA, Chow JT, Yang SC et al. (2000) Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non-small cell lung cancer. Cancer Res 60:3155–3159PubMedGoogle Scholar
  3. Albelda SM, Wiewrodt R, Zuckerman JB (2000) Gene therapy for lung disease: hype or hope? Ann Intern Med 132:649–660PubMedGoogle Scholar
  4. Albrechtsen N, Dornreiter I, Grosse F, Kim E, Wiesmüller L, Deppert W (1999) Maintenance of genomic integrity by p53: complementary roles for activated and non-activated p53. Oncogene 18:7706–7717PubMedGoogle Scholar
  5. Antonia SJ, Sotomayor E (2000) Gene therapy for lung cancer. Curr Opin Oncol 12:138–142PubMedGoogle Scholar
  6. Baker SJ, Fearon ER, Nigro JM et al. (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221PubMedGoogle Scholar
  7. Bartsch H, Hollstein M, Mustonen R et al. (1995) Screening for putative radon-specific p53 mutation hotspot in German uranium miners. Lancet 346:121PubMedGoogle Scholar
  8. Baselga J (1999) New horizons: gene therapy for cancer. Anticancer Drugs [Suppl 1] 10:S39–S42PubMedGoogle Scholar
  9. Bates S, Vousden K (1999) Mechanisms of p53-mediated apoptosis. Cell Mol Life Sci 55:28–37PubMedGoogle Scholar
  10. Benezra JM, Kornstein MJ, Grimes MM, Krystal G (1994) Small cell carcinomas of the lung express the Bcl-2 protein. Am J Pathol 145:1036–1040Google Scholar
  11. Bennett WP, Colby TV, Travis WD et al. (1993) p53 protein accumulates frequently in early bronchial neoplasia. Cancer Res 53:4817–4822PubMedGoogle Scholar
  12. Betz E, Papadopoulos T, Buchwald J, Dämmrich JR, MüllerHermelink HK (1995) Surfactant protein gene expression in metastatic and micrometastatic pulmonary adenocarein omas and other non small cell lung carcinomas: detection by reverse transcriptase-polymerase chain reaction. Cancer Res 55:4283–4286PubMedGoogle Scholar
  13. Biome O (1993) Geschichte, Ursachen und Verlaufs schilderung der “Schneeberger Lungenkrankheit” bzw. der Berufskrankheit Nr. 92 der ehemaligen Deutschen Demokratischen Republik/Nr. 2402 der Bundesrepublik Deutschland. BG 104:38–46Google Scholar
  14. Brennan J, O’Connor T, Makuch RW et al. (1991) Myc family amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimes. Cancer Res 51: 1708–1712PubMedGoogle Scholar
  15. Bülzebruck H, Drings P (1991) Classification of lung cancer: first experiences with the new TNM-dassification (4th edn). Eur Respir J 4:1197–2206PubMedGoogle Scholar
  16. Bülzebruck H, Bopp R, Drings P et al. (1992) New aspects in the staging of lung cancer: prospective validation of the International Union Against Cancer TNM dassification. Cancer 70:1102–1110PubMedGoogle Scholar
  17. Bunn PA, Soriano A, Helfrich BA et al. (2000) Her2/neu expression and effects of herceptin alone and in combination with cytotoxic agents in lung cancer. Proc Am Assoc Cancer Res 41:719Google Scholar
  18. Butz M (1999) Beruflich verursachte Krebserkrankungen-Eine Darstellung der im Zeitraum 1978 bis 1997 anerkannten Fälle. Hauptverband der gewerblichen Berufsgenossenschaften, Sankt AugustinGoogle Scholar
  19. Carbone DP (1997) The biology of the lung cancer. Semin Oncol 24:388–401PubMedGoogle Scholar
  20. Carbone DP (1999) Molecular modalities in the treatment of lung cancer. Oncology [Suppl 5] 13:142–147PubMedGoogle Scholar
  21. Chan DC, Soriano A, Kane MA, Helfrich B, Bunn PA (2000) Biology of lung cancer. In: Hansen H (ed) The IASLC textbook of lung cancer. Dunitz, London, pp 27–73Google Scholar
  22. Chiba I, Takahashi T, Nau MM et al. (1990) Mutations in the p53 gene are frequent in primary, resected non small lung cancer. Oncogene 5:1603–1606.PubMedGoogle Scholar
  23. Chin K, Ueda K, Pastan I, Gottesman M (1992) Modulation of activity of the promotor of the human MDRI gene by ras and p53. Science 255:459–462PubMedGoogle Scholar
  24. Chiu R, Boyle WJ, Meek J, Hunter T, Karin M (1988) The c-fos protein interacts with c-jun/AP-1 to stimulate transcription from AP-l responsive genes. Cell 54:541–542PubMedGoogle Scholar
  25. Chung GTY, Sundaresan V, Hasleton P, Rudd R, Taylor R, Rabbitts PH (1996) Clonal evolution of lung tumors. Cancer Res 56:1609–1614PubMedGoogle Scholar
  26. Dalquen P, Sauter G, Torhorst J et al. (1996) Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma. J Pathol 178:53–58PubMedGoogle Scholar
  27. Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY (1999) DNA damage-induced cell cyde checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene 18:7883–7899PubMedGoogle Scholar
  28. De Jong D, Prins FA, Mason DY, Reed JC, Van Ommen GB, Kluin PM (1994) Subcellular localization of the bd-2 protein in malignant and normal lymphoid cells. Cancer Res 54:256–260PubMedGoogle Scholar
  29. Denissenko MF, Pao A, Tang M, Pfeifer GP (1996) Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53. Science 274:430–432PubMedGoogle Scholar
  30. DePinhoo RA, Schreiber-Agus N, Alt FW (1991) Myc family oncogenes in the development of normal and neoplastic cells. Adv Cancer Res 57:1–46Google Scholar
  31. De Vos S, Miller CW, Takeuchi S, Gombart AF, Cho SK, Koeffler HP (1995) Alterations of CDKN2 (p16) in non-small celling cancer. Genes Chromosomes Cancer 14:164–170PubMedGoogle Scholar
  32. Disis ML, Cheever MA (1997) HER-2/neu protein: a target for antigen-specific immuntherapy of human cancer. Adv Cancer Res 71:343–371PubMedGoogle Scholar
  33. Dockhorn-Dworniczak B, Simon R, Brinkschmidt C, Poremba C, Böcker W (1998) Molekularbiologic maligner Tumorerkrankungen. Onkologe 4:671–681Google Scholar
  34. Dosaka-Akita H, Hu SX, Fujino M et al. (1997) Altered retinoblastoma protein expression in nonsmall cell lung cancer: its synergistic effects with altered ras and p53 protein status on prognosis. Cancer 79:1329–1337PubMedGoogle Scholar
  35. Drings P (1993) Diagnostics and staging as a basis for planning therapy in lung cancer. Gen Thorac Surg 14–24Google Scholar
  36. Ebina M, Steinberg SM, Mulshine JL, Linnoila RI (1994) Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer. Cancer Res 54:2496–2503PubMedGoogle Scholar
  37. El-Deiry WS, Tokino T, Velculescu VE et al. (1993) WAFI a potential mediator of p53 tumor suppression. Cell 75:817–825PubMedGoogle Scholar
  38. Fidler IJ (1997) Molecular biology of cancer: invasion and metastasis. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology. Lippincott-Raven, Philadelphia, pp 135–152Google Scholar
  39. Fields S, Jang S (1990) Presence of a potent transcription activating sequence in the p53 protein. Science 249:1046–1049PubMedGoogle Scholar
  40. Fisseler-Eckhoff A, Müller K-M (1992) Early cancer and preneoplastic lesions of the lung-extracellular matrix components. In: Bernal SD, Hesketh PJ (eds) Lung cancer differentiation. Implications for diagnosis and treatment. Dekker, New York, pp 78–89Google Scholar
  41. Fisseler-Eckhoff A, Müller K-M (1994) Pathologic der Pulmonalarterien bei Lungentumoren. Dtsch Med Wochenschr119:1415–1420PubMedGoogle Scholar
  42. Fong KM, Sekido Y, Minna JD (1999) Molecular pathogenesis of lung cancer. J Thorac Cardiovasc Surg 118:1136–1152PubMedGoogle Scholar
  43. Fontanini G, Bigini D, Vignati S et al. (1995a) Microvessel count predicts metastatic disease and survival in nonsmall cell lung cancer. J Pathol 177:57–63PubMedGoogle Scholar
  44. Fontanini G, Vignati S, Bigini D et al. (1995b) Bd-2 protein: a prognostic factor inversely correlated to p53 in nonsmall-cell lung cancer. Br J Cancer 71:1003–1007PubMedCentralPubMedGoogle Scholar
  45. Frederiksen KS, Petri A, Abrahamsen N, Poulsen HS (1999) Gene therapy for lung cancer. Lung Cancer 23:191–207PubMedGoogle Scholar
  46. Freedman DA, Levine AJ (1999) Regulation of the p53 protein by the MDM2 oncoprotein-Thirtyeight G. H. A. Clowes Memorial Award Lecture. Cancer Res 59:1–7PubMedGoogle Scholar
  47. Friend SH, Bernards R, Rogelj S et al. (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323:643–645PubMedGoogle Scholar
  48. Garziano SL, Cowan BY, Carney DN et al. (1987) Small cell lung cancer line derived from a primary tumor with a characteristic deletion of 3p. Cancer Res 48:2141–2155Google Scholar
  49. Gazdar AF (1994) The molecular and cellular basis of human lung cancer. Anticancer Res 14:261–267PubMedGoogle Scholar
  50. Gazdar AF, Carney DN, Nau MM, Minna JD (1985) Characterization of variant subdasses of cell line derived from small cell lung cancer having distinct biochemical, morphological and growth properties. Cancer Res 45:2924–2930PubMedGoogle Scholar
  51. Geddes DM (1979) The natural history of lung cancer: a review based on rates of tumor growth. Br J Dis Chest 73:1–17PubMedGoogle Scholar
  52. Giaccone G (1996) Oncogenes and antioncogenes in lung tumorigenesis. Chest 109:130S–134SPubMedGoogle Scholar
  53. Gonzales S, Basewitz DB von, Grundmann E, Nakhosteen JA, Müller K-M (1986) The ultrastructural heterogeneity of potentially preneoplastic lesions in the human bronchial mucosa. Pathol Res Pract 181:408–417Google Scholar
  54. Greenblatt MS, Bennett WP, Hollstein M, Harris CC (1994) Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:4855–4878PubMedGoogle Scholar
  55. Griffin CA, Baylin SB (1985) Expression of the c-myb oncogene in human small cell lung carcinoma. Cancer Res 45:272–275PubMedGoogle Scholar
  56. Hajj C, Akoum R, Bradley E, Paquin F, Ayoub J (1990) DNA alterations at proto oncogene loci and their clinical significance in operable non small cell lung cancer. Cancer 66:733–739PubMedGoogle Scholar
  57. Harbour JW, Lai SI, Whang-Peng J, Gazdar AF, Minna JD, Kaye FJ (1988) Abnormalities in structure and expression of the retinoblastoma gene in SCLC. Science 241:353–357PubMedGoogle Scholar
  58. Hasimoto T, Tokuchi Y, Hayashi M et al. (1999) p53 null mutations undetected by immunohistochemical staining predict a poor outcome with early-stage non-small cell lung carcinomas. Cancer Res 59:5572–5577Google Scholar
  59. Haugen A (2000) Etiology of lung cancer. In: Hansen H (ed) The IASLC textbook of lung cancer. Dunitz, London, pp 1–12Google Scholar
  60. Hermanek P, Hutter RVP, Sobin LH, Wittekind C (1999) Classification of isolated tumor cells and micrometastasis. Cancer 86:2668–2673PubMedGoogle Scholar
  61. Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R (1994) Retinoblastoma protein expression in lung cancer: an immunohistochemical analysis. Oncology 51:544–551PubMedGoogle Scholar
  62. Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R (1995) High prevalence of bcl-2 oncoprotein expression in small cell lung cancer. Anticancer Res 15:503–505PubMedGoogle Scholar
  63. Higashiyama M, Doi O, Kodama K et al. (1997) MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. Br J Cancer 75:1302–1308PubMedCentralPubMedGoogle Scholar
  64. Hirsch FR, Matthews MI, Aisner S et al. (1988) Histopathologic classification of small cell lung cancer.Changing concepts and terminology. Cancer 62:973–977PubMedGoogle Scholar
  65. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane proteine that blocks programmed cell death. Nature 348:334–336PubMedGoogle Scholar
  66. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancer. Science 253:362–366Google Scholar
  67. Hollstein M, Shomer B, Greenblatt M et al. (1996) Somatic point mutations in the p53 gene of human tumors and cell lines. Updated compilation. Nucleic Acids Res 24:141–146Google Scholar
  68. Hollstein M, Bartsch H, Wesch H et al. (1997a) p53 gene mutation analysis in tumors of patients exposed to a-particles. Carcinogenesis 18:511–516PubMedGoogle Scholar
  69. Hollstein M, Soussi T, Thomas G, Brevern M-C von, Bartsch H (1997b) P53 gene alterations in human tumors: perspectives for cancer control. Rec Results Cancer Res 143:370–389Google Scholar
  70. Horio Y, Takahashi,Kuroishi T et al. (1993) Prognostic significance of p53 mutations and 3p deletions in primary resected non-small cell lung cancer. Cancer Res 53:1–4PubMedGoogle Scholar
  71. Horowitz JM, Park SH, Bogenmann E et al. (1990) Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells. Proc Natl Acad Sci USA 87:2775–2779PubMedCentralPubMedGoogle Scholar
  72. Höfler H (1997) Spektrum neuro endokriner Tumoren der Lunge. Pathologe 18:322–323Google Scholar
  73. Husgafvel-Pursiainen K, Hackman P, Ridanpaa M et al. (1993) K-ras mutations in human adenocarcinoma of the lung-association with smoking and occupational exposure to asbestos. Int J Cancer 53:250–256PubMedGoogle Scholar
  74. Hussain SP, Harris CC (1998) Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes. Cancer Res 58:4023–4037PubMedGoogle Scholar
  75. Iggo R, Gatter K, Bartek J, Lane DP, Harris AL (1990) Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 355:675–679Google Scholar
  76. Janus F, Albrechtsen N, Dornreiter I, Wies müller L, Grosse F, Deppert W (1999) The dual role model for p53 in maintaining genomie integrity. Cell Mol Life Sci 55:12–27PubMedGoogle Scholar
  77. Johnson B, Ihde D, Makuch RW et al. (1987) Myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. J Clin Invest 79:1629–1634PubMedCentralPubMedGoogle Scholar
  78. Junker K, Müller K-M (1989) Metastasierungsmuster beim Bronchialkarzinom. Z Herz Thorax Gefäßchir 3:189–194Google Scholar
  79. Junker K, Krapp D, Müller K-M (1995) Kleinzelliges Bronchialkarzinom nach ChemoTherapic. Pathologe 16:217–222PubMedGoogle Scholar
  80. Junker K, Thomas M, Schulmann K, Klinke F, Bosse U, Müller K-M (1997a) Tumor regression in non-small cell lung cancer following neoadjuvant therapy-histological assessment. J Cancer Res Clin Oncol 123:469–477PubMedGoogle Scholar
  81. Junker K, Thomas M, Schulmann K, Klinke V, Bosse U, Müller K-M (1997b) Regressionsgrading neoadjuvant behandelter niehtkleinzelliger Lungentumoren. Pathologe 18: 131–140PubMedGoogle Scholar
  82. Kamp A, Gruis NA, Weaver-Feldhaus J et al. (1994) A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–440Google Scholar
  83. Kaufmann O, Dietel M (2000) Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B. Histopathology 36:8–16PubMedGoogle Scholar
  84. Kern JA, Torney L, Nordberg JE, Weiner DB, Greene MI, Robinson RA (1990) p185neu expression in lung adenocarcinomas predicts shortened survival. Cancer Res 50:5184–5191PubMedGoogle Scholar
  85. Kern JA, Robinson RA, Gazdar A, Torney L, Weiner DB (1992) Mechanisms of p185HER2 expression in human non-small cell lung cancer cell lines. Am J Respir Cell Mol Biol 6:359–363PubMedGoogle Scholar
  86. Kiefer PE, Bepler G, Kubasch M, Havemann K (1987) Amplification and expression of protooncogenes in human small cell lung cancer cell lines. Cancer Res 47:6236–6242PubMedGoogle Scholar
  87. Kikuchi M (1999) Retropharyngeal rhabdomyosarcoma mimicking pseudotumor cerebri. Pediatr Neurol 21:496–499PubMedGoogle Scholar
  88. Knudson AG JR (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823PubMedCentralPubMedGoogle Scholar
  89. Koechli OR, Schaer GN, Scifert B et al. (1994) Mutant p53 protein associated with chemosensitivity in breast cancer specimens. Lancet 344: 1647–1648PubMedGoogle Scholar
  90. Kok K, Osinga J, Carritt B et al. (1987) Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature 330:578–581PubMedGoogle Scholar
  91. Krajewski S, Tanaka S, Takayama S, Schibier M, Fenton W, Reed JC (1993) Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmatic reticulum, and outer mitochondrial membrane. Cancer Res 53:4701–47l4PubMedGoogle Scholar
  92. Kreuzer M, Kreienbrock L, Gerken M et al. (1998) Risk factors for lung cancer in young adults. Am J Epidemiol 147:1028–1037PubMedGoogle Scholar
  93. Kreuzer M, Müller K-M, Gerken M, Wiehmann H-E (1999) Lung cancer histologie types and age of onset. Cancer 85: 1958–1965PubMedGoogle Scholar
  94. Kwiatkowski DJ, Harpole DH, Godleski J et al. (1998) Molecular pathologic substaging in 244 stage I non-small cell lung cancer patients. J Clin Oncol 16:2468–2477PubMedGoogle Scholar
  95. Lakin ND, Jackson SP (1999) Regulation of p53 in response to DNA damage. Oncogene 18:7644–7655PubMedGoogle Scholar
  96. Leach FS, Tokino T, Meltzer P et al. (1993) p53 Mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res 53:2231–2234PubMedGoogle Scholar
  97. Lee W, Mitchell P, Tjian R (1987) Purified transcription factor AP-l interacts with TPA-indueible elements. Cell 49:741–752PubMedGoogle Scholar
  98. Levine AJ, Chang AW, Dittmer D et al. (1994a) The p53 tumor suppressor gene. J Lab Clin Med 123:817–823PubMedGoogle Scholar
  99. Levine AJ, Perry ME, Chang A, Silver A, Dittmer D, Wu M (1994b) The 1993 Walter Hubert Lecture-the role of the p53 tumour suppressor gene in tumorigenesis. Br J Cancer 69:409–416PubMedCentralPubMedGoogle Scholar
  100. Lichtenstein P, Holm NV, Verkasalo PK et al. (2000) Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85PubMedGoogle Scholar
  101. Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD (1983) Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature 306:194–196PubMedGoogle Scholar
  102. Lotem J, Sachs L (1993) Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation competent and differentiation-defective myeloid leukemic cells. Cell Growth Differ 4:41–47PubMedGoogle Scholar
  103. Lubin R, Zalcman G, Bouchet L et al. (1995) Serum p53 antibodies as early markers of lung cancer. Nat Med1:701–702PubMedGoogle Scholar
  104. Mannino DM, Ford E, Giovanni GA, Thun M (1998) Lung cancer deaths in the United States from 1979 to 1992: an analysis using multiple-cause mortality data. Int J Epidemiol 27:159–166PubMedGoogle Scholar
  105. Marchetti A, Doglioni C, Barbareschi M et al. (1996) p21 RNA and protein expression in non-small cell lung carcinomas: evidence of p53-independent expression and associatiOn with tumoral differentiation. Oncogene 12:1319–1324PubMedGoogle Scholar
  106. May P, May E (1999) Twenty years of p53 research: structural and functional aspects of the p53 protein [published erratum appears in Oncogene 2000 23:1734]. Oncogene 18:7621–7636PubMedGoogle Scholar
  107. McDowell EM (1987) Bronchogenie carcinomas. In: McDoweil EM (ed) Current problems in tumor pathology, lung carcinomas. Churchill Livingstone, Harlow, pp 255–285Google Scholar
  108. McLaren R, Kuzu I, Dunnill M, Harris CC, Lane DP, Gatter KC (1992) The relationship of p53 immunostaining to survival in carcinoma of the lung. Br J Cancer 66:735–738PubMedCentralPubMedGoogle Scholar
  109. Mitsudomi T, Viallet J, Mulshine J, Linnoila R, Minna JD, Gazdar AF (1991) Mutations of ras genes distinguish a subset of non-small-cell lung cancer cell lines from small-cell lung cancer cell lines. Oncogene 6: 1353–1362PubMedGoogle Scholar
  110. Miwa W, Yasuda J, Yashima K, Makino R, Sekiya T (1994) Absence of activating mutations of the rRAF1 protooncogene in human lung cancer. Biol Chem 375:705–709Google Scholar
  111. Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293–299PubMedGoogle Scholar
  112. Miyashita T, Krajewski S, Krajewska M, Reed J (1994) Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799–1805PubMedGoogle Scholar
  113. Momand J, Zambetti G, Olson D, Levine A (1992) The mdm2 oncogene product forms a complex with the p53 protein and inhibits p53 mediated transactivation. Cell 69:1237–1245PubMedGoogle Scholar
  114. Mountain CF (1986) A new international staging-system for lung cancer. Chest [Suppl] 98:225–232Google Scholar
  115. Mountain CF (1996) Lung cancer staging: 1997 revisions. In: Antypas G (ed) 2nd International Congress on Lung Cancer. Monduzzi, Bologna, pp 11–13Google Scholar
  116. Mountain CF (1997) Revisions in the international system for staging lung cancer. Chest 111: 1710–1717PubMedGoogle Scholar
  117. Müller K-M (1988) Early cancer of the lung. Recent Results Cancer Res 106:119–130PubMedGoogle Scholar
  118. Müller K-M (1999) Neues zur Pathologie der Lungentumoren. Verh Dtsch Ges Pathol 83:168–183PubMedGoogle Scholar
  119. Müller K-M, Fisseler-Eckhoff A (1998) Pathologie der Lungentumoren. In: Drings P, Vogt-Moykopf I (Hrsg) Thoraxtumoren: Diagnostik-Staging-gegenwärtiges Therapickonzept, 2. Aufl. Springer, Berlin Heidelberg New York, S 3–34Google Scholar
  120. Müller K-M, Menne R (1985) Small cell carcinoma of the lung: pathological anatomy. Recent Results Cancer Res 97:11–24PubMedGoogle Scholar
  121. Müller K-M, Brämer UG, Hiddemann W (1986) Probleme der morphologischen Klassifikation bösartiger Lungentumoren. Atemw Lungenkrkh 12:459–465Google Scholar
  122. Müller K-M, Fisseler-Eckhoff A, Reitemeyer E (1988) Stromareaktionen in Lungentumoren-Tumorvernarbung und sogenanntes Narbenkarzinom. Fortsehr Med 106:19–24Google Scholar
  123. Müller K-M, Junker K, Stief A (1993) Wert und Bedeutung pathologisch-anatomischer Befunde für die Thoraxchirurgie. In: Vogt-Moykopf I, Drings P (Hrsg) Thoraxchirurgie-Stand und Ausbliek. Steinkopff, Darmstadt, S 23–35Google Scholar
  124. Müller K-M, Junker K, Wiethege Th (1995) Niehtkleinzellige Lungentumoren-Morphologie, Tumorregression, Molekularpathologie. Onkologe 1:429–440Google Scholar
  125. Müller K-M, Wiethege Th, Junker K (1998) Pathologie kleinzelliger Lungentumoren. Onkologe 4:996–1004Google Scholar
  126. Noble J, Willetts K, Mercer W, Reddel R (1992) Effects of exogenous wild-type p53 on a human lung carcinoma cell line with endogenous wild-type p53. Exp Cell Res 203:297–304PubMedGoogle Scholar
  127. Nobori T, Miura K, Wu D, Carson D (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368:753–756PubMedGoogle Scholar
  128. Nuorva K, Soini Y, Kamel D et al. (1993) Concurrent p53 expression in bronchial dysplasias and squamous cell lung carcinomas. Am J Pathol 142:725–732PubMedCentralPubMedGoogle Scholar
  129. Ohsaki Y, Toyoshima E, Fujiuchi S et al. (1996) Bcl-2 and p53 protein expression in non-small cell lung cancers: correlation with survival time. Clin Cancer Res 2:915–920PubMedGoogle Scholar
  130. Okamoto A, Hussain SP, Hagiwara K et al. (1995) Mutations in the p16(INK4)/MTS1/CDKN2, pI5(INK4B)/MTS2, and p18 genes in primary and metastatic lung cancer. Cancer Res 55:1448–1451PubMedGoogle Scholar
  131. Oren M, Rotter V (1999) p53-the first twenty years. Cell Mol Life Sci 55:9–11PubMedGoogle Scholar
  132. Pantel K, Knebel-Boeberitz MV, Izbicki JR, Riethmüller G (1997) Disseminierte Tumorzellen: Diagnostik, prognostische Relevanz, Phänotypisierung und therapeutische Strategien. Chirurg 67:1241–1250Google Scholar
  133. Pappai G, Pöhl CD (1999) Uranerzbergbau und Berufsgenossenschaften: Das Berufskrankheitengeschehen der ehemaligen Wismut-Beschäftigten. BG 110:596–602Google Scholar
  134. Petersen I, Langreck H, Wolf G et al. (1996) Small cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 1Oq, 13q, and 17p. Br J Cancer 75:79–86Google Scholar
  135. Petersen I, Bujard M, Petersen S et al. (1997) Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung. Cancer Res 57:2331–2335PubMedGoogle Scholar
  136. Petit AM, Rak J, Hung MC et al. (1997) Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 151:1523–1530PubMedCentralPubMedGoogle Scholar
  137. Pezzella F, Turley H, Kuzu I et al. (1993) Bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med 329:690–694PubMedGoogle Scholar
  138. Pohlabeln H, Jöckel K, Müller K-M (1997) The relation between various histological types of lung cancer and the number of years since cessation of smoking. Lung Cancer 18:223–229PubMedGoogle Scholar
  139. Quinlan DC, Davidson A, Summers C, Warden H, Doshi H (1992) Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res 52:4828–4831PubMedGoogle Scholar
  140. Quintinilla M, Bron K, Ramsden N, Balmain A (1986) Carcinogen-specific mutation and amplification of H-ras during mouse skin carcinogenesis. Nature 322:78–80Google Scholar
  141. Rachwal WJ, Bongiorno PF, Orringer MB, Whyte RI, Ethier SP, Beer DG (1995) Expression and activation of erbB-2 and epidermal growth factor receptor in lung adenocarcinomas. Br J Cancer 72:56–64PubMedCentralPubMedGoogle Scholar
  142. Rak J, Mitsuhashi Y, Bayko L et al. (1995) Mutant ras oncogenes upregulate VEGFJVPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res 55:4575–4580PubMedGoogle Scholar
  143. Ransonne LJ, Verma IM (1990) Nuclear oncogenes fos and jun. Annu Rev Cell Biol 6:539–557Google Scholar
  144. Raycroft L, Wu HY, Lozano G (1990) Transcriptional activation by wild type but not transforming mutants of the p53 anti oncogene. Science 249:1049–1051PubMedCentralPubMedGoogle Scholar
  145. Reissmann PT, Koga H, Takahashi R et al. (1993) Inactivation of the retinoblastoma susceptibility gene in nonsmall-cell lung cancer. The Lung Cancer Study Group. Oncogene 8:1913–1919PubMedGoogle Scholar
  146. Rodenhuis S, Van de Wetering ML, Mooi WJ, Evers S, Zandwijk N van, Bos JL (1987) Mutational activation of the kras oncogene: a possible pathogenic factor in adenocarcinoma of the lung. N Engl J Med 317:929–935PubMedGoogle Scholar
  147. Rodenhuis S, Siebos RJC, Boot AJ et al. (1988) Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 48:5738–5741PubMedGoogle Scholar
  148. Rosell R, Gomez-Codina J, Camps C et al. (1994) A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 330:153–158PubMedGoogle Scholar
  149. Roth JA (1995) Molecular events in lung cancer. Lung Cancer 12:S3–S15PubMedGoogle Scholar
  150. Roth JA, Fossella F, Komaki R et al. (1994) A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Nat Cancer Inst 86:673–680PubMedGoogle Scholar
  151. Rusch V, Klimstra D, Venkatraman E et al. (1995) Aberrant p53 expression predicts clinical resistance to cisplatinbased chemotherapy in locally advanced non-small cell lung cancer. Cancer Res 55:5038–5042PubMedGoogle Scholar
  152. Rygaard K, Nakamura T, Sang-Thomsen M (1993) Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stern cell factor, in SCLC cell lines and xenografts. Br J Cancer 67:37–46PubMedCentralPubMedGoogle Scholar
  153. Schirren CI (1996) Die systematische mediastinale Lymphknotendissektion beim Bronchialkarzinom-Indikation, Technik und Ergebnisse. Habilitationsschrift, RuprechtKarl-Universität HeidelbergGoogle Scholar
  154. Schmitz I, Fisseler-Eckhoff A, Erfkamp S, Twent U, Müller K-M, Becker H (1994) Characterization of cytokeratin expression in squamous cell carcinoma of the lung-immunohistochemical and electronmicroscopical investigations. In: Antypas G (ed) International Congress for Lung Cancer. Monduzzi, Bologna, S 123–127Google Scholar
  155. Schraufnagel DE (1990) Electron microscopy of the lung. Dekker, New YorkGoogle Scholar
  156. Schuette J, Nau M, Birrer M, Thomas F, Gazdar AF, Minna JD (1988) Constitutive expression of multiple mRNA forms of the c-jun oncogene in human lung cancer cell lines. Proc Am Assoc Cancer Res 29:455Google Scholar
  157. Sekido Y, Obata Y, Ueda R et al. (1991) Preferential expression of c-kit protooncogene transscripts in small cell lung cancer. Cancer Res 51:2416–2419PubMedGoogle Scholar
  158. Selter H, Montenarh M (1994) The emerging picture of p53. Int Arch Occup Environ Health 26:145–154Google Scholar
  159. Selter H, Amela-Neuschwander S, Villena-Heinsen C, Montenarh M (1995) Antibodies against murine double minute-2 (mdm2) in sera of patients with various gynaecological diseases. Cancer Lett 96: 111–115PubMedGoogle Scholar
  160. Shapiro GI, Edward CD, Kobzik L et al. (1995) Reciprocal Rb inactivation and p16(INK4) expression in primary lung cancers and cell lines. Cancer Res 55:505–509PubMedGoogle Scholar
  161. Shew JY, Chen PL, Bookstein R, Lee EY (1990) Deletion of a splice donor site ablates expression of the following exons and produces an unphosphorylated RB protein unable to bind SV40 T antigen. Cell Growth Differ 1:17–25PubMedGoogle Scholar
  162. Shimizu E, Coxon A, Otterson GA et al. (1994) RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma. Oncogene 9:2441–2448PubMedGoogle Scholar
  163. Shows TB, McAlpine PJ, Boucher C et al. (1987) Guidelines for human gene nomenclature. An international system for human gene nomenclature (ISGN, 1987). Cytogenet Cell Genet 46:11–28PubMedGoogle Scholar
  164. Siegfried JM, Davis AJ, Gubish CT et al. (1998) Growth factors and recepetors in non-small cell lung cancer. In: Kane MA, Bunn PA (eds) Biology of lung cancer. Dekker, New York, S 317–336Google Scholar
  165. Slamon DJ, Godolphin W, Jones LA et al. (1989) Studies of the HER-2/neu protooncogene in human breast and ovarian cancer. Science 244:707–712PubMedGoogle Scholar
  166. Slamon DJ, Leyland-Jones B, Shak S et al. (1998) Addition of herceptin (humanized anti Her2 antibody) to first line chemotherapy for Her2 overexpressing metastatic breast cancer markedly increases antieancer activity: a randomized multinational controlled phase III trials. Proc Am Soc Clin Onco117:98aGoogle Scholar
  167. Siebos RJ, Kibbelaar RE, Dalesio O et al. (1990) K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 323:561–565Google Scholar
  168. Soini Y, Kamel D, Nuorva K, Lane DP, Vähäkangas K, Pääkko P (1992) Low p53 protein expression in salivary gland tumours compared with lung carcinomas. Virchows Arch 421:415–420Google Scholar
  169. Soussi T (2000) p53 antibodies in the sera of patients with various types of cancer: a review. Cancer Res 60:1777–1788PubMedGoogle Scholar
  170. Sozzi G, Veronese ML, Negrini M et al. (1996) The FHIT gene 3p14.2 is abnormal in lung cancer. Cell 85:17–26PubMedGoogle Scholar
  171. Sugio K, Kishimoto Y, Virmani AK, Hung JY, Gazdar AF (1994) K-ras mutations are a relatively late event in the pathogenesis of lung carcinomas. Cancer Res 54:5811–5815PubMedGoogle Scholar
  172. Szabo E, Riffe ME, Steinberg SM, Birrer MJ, Linnoila RI (1996) Altered cJUN expression: an early event in human lung careinogenesis. Cancer Res 56:305–315PubMedGoogle Scholar
  173. Taylor JA, Watson MA, Devereux TR, Michels RY, Saccomanno G, Anderson M (1994) P53 mutation hotspot in radon-associated lung cancer. Lancet 343:86–87PubMedGoogle Scholar
  174. Thomas M, Rübe C, Semik M et al. (1999) Impact of preoperative bimodality induction including twice-daily-radiation on tumor regression and survival in stage III non-small-cell lung cancer. J Clin Oncol 17:1185–1193PubMedGoogle Scholar
  175. Thottassery JV, Zambetti GP, Arimori K, Schuetz EG, Schuetz JD (1997) p53-dependent regulation of MDRI gene expression causes selective resistance to chemotherapeutic agents. Proc Natl Acad Sci USA 94:11037–11042PubMedCentralPubMedGoogle Scholar
  176. Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E, collaborators from 14 countries (1999) histological typing of lung and pleural tumors, 3rd edn. Springer, Berlin Heidelberg New YorkGoogle Scholar
  177. True LD (1990) Atlas of diagnostic immunohistopathology. Lippincott, PhiladelphiaGoogle Scholar
  178. Tseng JE, Rodriguez M, Ro J, Liu D, Hong WK, Mao L (1999) Gender differences in pS3 mutational status in small cell lung cancer. Cancer Res 59:5666–5670PubMedGoogle Scholar
  179. Tsujimoto Y, Cossman J, Jaffe E, Croce CM (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440–1443PubMedGoogle Scholar
  180. Vähäkangas KH, Samet JM, Lane DP, Harris CC et al. (1992) Mutations of p53 and ras gene in radon associated lung cancer from uranium miners. Lancet 339:576–580PubMedGoogle Scholar
  181. Volm M, Efferth T, Mattem J (1992) Oncoprotein (c-myc, cerbB1, c-erbB2, c-fos) and suppressor gene products (p53) gene expression in squamous cell carcinomas of the lung. Clinical and biological correlations. Anticancer Res 12:11–20PubMedGoogle Scholar
  182. Volm M, Drings P, Mattem J, Wodrieh W (1993a) Prognostic value of oncoproteins for the survival of patients with non-small cell lung carcinomas. Int J Cancer 2:767–772Google Scholar
  183. Volm M, Drings P, Wodrieh W (1993b) prognostic significance of the expression of c-fos, c-jun and erbB-1 oncogene products in human squamous cell lung carcinomas. J Cancer Res Clin Oncol 119:507–510PubMedGoogle Scholar
  184. Volm M, Vogt-Moykopf I, Wodrieh W (1993c) C-K-ras and c-N-ras are important and stage-independent prognostic indicators in adenocarcinomas of the lung. Cancer J Sci Am 6:37–42Google Scholar
  185. Walker C, Robertson L, Myskow M, Dixon G (1995) Expression of the BCL-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas. Br J Cancer72:164–169PubMedCentralPubMedGoogle Scholar
  186. Wallace-Brodeur RR, Lowe SW (1999) Clinical implications of p53 mutations. Cell Mol Life Sci 55:64–75PubMedGoogle Scholar
  187. Weidner N (1995) Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 147:9–19PubMedCentralPubMedGoogle Scholar
  188. Wen D, Peles E, Cuppies R et al. (1992) Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin ho molo gy unit. Cell 69:559–572PubMedGoogle Scholar
  189. Whang-Peng J, Kao-Shan CS, Lee EC et al. (1982) Specific chromosome defects associated with human small-cell lung cancer; deletion 3p(14-23). Science 215:181–182PubMedGoogle Scholar
  190. Wiethege Th, Voss B, Müller K-M (1994) Immunhistochemische Untersuchungen zur Akkumulation des TumorSuppressor-Gens p53 in Bronchialkarzinomen. Atemw Lungenkrkh 20:326–328Google Scholar
  191. World Health Organization (1981) International histological classification of tumours No. 1, 2nd edn. World Health Organization, GenevaGoogle Scholar
  192. World Health Organization (1982) The World Health Organization histologic al typing of lung tumours-2nd edn.Am J Clin Pathol 77:123–136Google Scholar
  193. Wu GS, Eldeiry WS (1996) P53 and chemosensitivity. Nat Med 2:255–256PubMedGoogle Scholar
  194. Xiao S, Li D, Corson J, Vijg J, Fleteher JA (1995) Codeletion of pl5 and pl6 genes in primary non-small cell lung cancer. Cancer Res 55:2968–2971PubMedGoogle Scholar
  195. Xu H, Cagle P, Hu S et al. (1995) Altered retinoblastoma (RB) and p53 protein status as a synergistie prognostic factor in non-small cell lung carcinoma. Proc Am Assoc Cancer Res 36:246Google Scholar
  196. Yang Q, Wesch H, Müller K-M, Bartsch H, Wegener K, Hollstein M (1999) Analysis of radon-associated squamous cell carcinomas of the lung for a p53 gene hot spot mutation. Br J Cancer 82:763–766Google Scholar
  197. Yap DB, Hsieh JK, Chan FS, Lu X (1999) mdm2: a bridge over the two tumour suppressors, p53 and Rb. Oncogene 18:7681–7689PubMedGoogle Scholar
  198. Yokota J, Wada M, Shimosato Y, Terada M, Sugimura T (1987) Loss of heterozygosity on chromosomes 3, 13, and 17 in small ceH carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci USA 84:9252–9256PubMedCentralPubMedGoogle Scholar
  199. Yokota J, Shimosato Y, Sugimura T, Terada M (1988) Altered expression of the retinoblastoma (RB) gene in small cell carcinoma of the lung. Oncogene 3:471–475PubMedGoogle Scholar
  200. You H, Candrian U, Maronpot RR, Stoner GD, Anderson MW (2000) Activation of Ki-ras protooncogene in spontaneously occurring and chemically induced lung tumors of strain A mouse. Proc Natl Acad Sci USA 86:3070–3074Google Scholar
  201. Zangemeister-Wittke U, Stahel RA (1999) Novel approaches to the treatment of small-cell lung cancer. Cell Mol Life Sci 55:1585–1598PubMedGoogle Scholar
  202. Babcock TL, Powell DH, Bothwell RS (1976) Radiation-induced peritoneal mesothelioma. J Surg Oncol 8:369–372PubMedGoogle Scholar
  203. Balsara BR, Bell DW, Sonoda G et al. (1999) Comparative genomic hybridization and loss of heterozygosity analyses identify a common region of deletion at 15q 11.1-15 in human malignant mesothelioma. Cancer Res 59:450–454PubMedGoogle Scholar
  204. Baris I, Artvinli M, Sahin AA (1979) Environmental mesothelioma in Turkey. Ann N Y Acad Sci 330:432Google Scholar
  205. Baris I, Simonato L, Artvinli M et al. (1987) Epidemiological and environmental evidence of the health effects of exposure to erionite fibres: a four-year study of the Cappadoeian region of Turkey. Int J Cancer 39:10–17PubMedGoogle Scholar
  206. Battifora H, McCaughey WTE (1995) Tumors of the serosal membran es, 3rd edn. Armed Forces Institute of Pathology, Washington, DCGoogle Scholar
  207. Beer TW, Buchanan R, Matthews AW, Stradling R, Pullinger N, Pethybridge RJ (1998) Prognosis in malignant mesothelioma related to MIB 1 proliferation index and histological subtype. Hum Pathol 29:246–251PubMedGoogle Scholar
  208. Bell DW, Jhanwar SC, Testa JR (1997) Multiple regions of allelic loss from chromosome arm 6q in malignant mesothelioma. Cancer Res 57:4057–4062PubMedGoogle Scholar
  209. Berman JJ, Rice JM (1979) Mesotheliomas and proliferative lesions of the testicular mesothelium in Fischer, SpragueDawley and Buffalo rats by methyl(acetoxymethyl)-nitrosamine (DMN-OAc). Vet Pathol 16:574–582PubMedGoogle Scholar
  210. Bermudez E, Everitt J, Walker C (1990) Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture. Exp Cell Res 190:91–98PubMedGoogle Scholar
  211. Bianchi C, Brollo A, Zuch C (1993) Asbestos-related familial mesothelioma. Eur J Cancer Prev 2:247–250PubMedGoogle Scholar
  212. Bianchi AB, Mitsunaga SI, Cheng JQ et al. (1995) High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci USA 92:10854–10858PubMedCentralPubMedGoogle Scholar
  213. Bjorkqvist AM, Tammilehto L, Anttila S, Mattson K, Knuutila S (1997) 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 75:523–527PubMedCentralPubMedGoogle Scholar
  214. Bjorkqvist AM, Tammilehto L, Nordling S et al. (1998) Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung. Br J Cancer 77:260–269PubMedGoogle Scholar
  215. Bjorkqvist AM, Wolf M, Nordling S et al. (1999) Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis. Br J Cancer 81:1111–1115PubMedCentralPubMedGoogle Scholar
  216. Bonn D (1999) Mesothelioma deaths may double within 20 years. Lancet 353:383Google Scholar
  217. Boutin C, Rey F, Viallat JR (1995) Prevention of malignant see ding after invasive diagnostic procedures in patients with pleural mesothelioma: a randomized trial of local radiotherapy. Chest 108:754–758PubMedGoogle Scholar
  218. Brenner J, Sordillo PP, Magill GB, Golbey RB (1982) Malignant mesothelioma of the pleura: review of 123 patients. Cancer 49:2431–2435PubMedGoogle Scholar
  219. Brinkmann OA, Müller KM (1989) What’s new in intraperitoneal test on Kevlar (asbestos substitute)? Pathol Res Pract 185:412–417PubMedGoogle Scholar
  220. Brown JW, Kristensen KAB, Monroe LS (1968) Peritoneal mesothelioma following pneumoperitoneum maintained for twelve years: report of a case. Am J Dig Dis 13:830–835PubMedGoogle Scholar
  221. Bültzingslöwen F von, Siernon G (1999) Die Therapic des malignen Pleuramesothelioms-ein fortdauerndes Dilemma. Pneumologie 53:266–275Google Scholar
  222. Caminschi I, Venetsanakos E, Leong CC, Garlepp MJ, Robinson BW, Scott B (1999) Cytokine gene therapy of mesothelioma. Immune and antitumor effects of transfected interleukin-12. Am J Respir Cell Mol Biol 21:347–356PubMedGoogle Scholar
  223. Carbone M, Pass HI, Rizzo P et al. (1994) Simian virus 40-like DNA sequences in human pleural mesothelioma. Oncogene 9: 1781–1790PubMedGoogle Scholar
  224. Carbone M, Rizzo P, Grimley PM et al. (1997a) Simian virus-40 large-T antigen binds p53 in human mesotheliomas. Nat Med 3:908–912PubMedGoogle Scholar
  225. Carbone M, Rizzo P, Pass HI (1997b) Simian virus 40, poliovaccines and human tumors: a review of recent developments. Oncogene 15:1877–1888PubMedGoogle Scholar
  226. Center R, Lukeis R, Dietzsch E, Gillespie M, Garson OM (1993) Molecular deletion of 9p sequences in non-small cell lung cancer and malignant mesothelioma. Genes Chromosomes Cancer 7:47–53PubMedGoogle Scholar
  227. Cheng JQ, Jhanwar SC, Lu YY, Testa JR (1993) Homozygous deletions within 9p21-p22 identify a small critical region of chromosomal loss in human malignant mesotheliomas. Cancer Res 53:4761–4763PubMedGoogle Scholar
  228. Cheng JQ, Jhanwar SC, Klein WM et al. (1994) p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res 54:5547–5551PubMedGoogle Scholar
  229. Cicala C, Pompetti F, Nguyen P, Dixon K, Levine AS, Carbone M (1992) SV40 small t deletion mutants preferentially transform mononueIear phagocytes and B lymphocytes in vivo. Virology 190:475–479PubMedGoogle Scholar
  230. Cicala C, Pompetti F, Carbone M (1993) SV40 induces mesotheliomas in hamsters. Am J Pathol 142:1524–1533PubMedCentralPubMedGoogle Scholar
  231. Cristaudo A, Vivaldi A, Sensales G et al. (1995) Molecular biology studies on mesothelioma tumor samples: preliminary data on H-ras, p21, and SV40. J Environ Pathol Toxicol Oncol 14:29–34PubMedGoogle Scholar
  232. Dawson A, Gibbs A, Browne K, Pooley F, Griffiths M (1992) Familial mesothelioma. Details of 17 cases with histopathologic findings and mineral analysis. Cancer 70: 1183–1187PubMedGoogle Scholar
  233. De Luca A, Baldi A, Esposito V et al. (1997) The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas. Nat Med 3:913–916PubMedGoogle Scholar
  234. Donna A, Betta PG (1982) Mesodermomas: a new embryological approach to primary tumours of coelomic surfaces. Histopathology 5:31–44Google Scholar
  235. Donna A, Betta PG (1986) Differentiation towards cartilage and bone in a primary tumour of pleura. Further evidence in support of the concept of “mesodermoma”. Histopathology 10:101–108PubMedGoogle Scholar
  236. Donna A, Betta PG, Bianchi V et al. (1991) A new insight into the histogenesis of “mesodermomas”-malignant mesotheliomas. Histopathology 19:239–244PubMedGoogle Scholar
  237. Elmes PC, Simpson JC (1976) The clinical aspects of mesothelioma. QJM 45:427–429PubMedGoogle Scholar
  238. Fitzpatrick DR, Bielefeldt-Ohmann H, Himheck RP, Jarnicki AG, Marzo AL, Robinson BW (1994) Transforming growth factor-beta: antisense RNA-mediated inhibition affects anchorage-independent growth, tumorigenicity and tumor-infiltrating T-cells in malignant mesothelioma. Growth Factors 11:29–44PubMedGoogle Scholar
  239. Flejter WL, Li FP, Antman KH, Testa JR (1989) Recurring loss involving chromosomes 1, 3, and 22 in malignant mesothelioma: possible sites of tumor suppressor genes.Genes Chromosomes Cancer 1:148–154PubMedGoogle Scholar
  240. Frizelle SP, Grim J, Zhou J et al. (1998) Re-expression of p16INK4a in mesothelioma cells results in cell cycle arrest, cell death, tumor suppression and tumor regression. Oncogene 16:3087–3095PubMedGoogle Scholar
  241. Gilks B, Hegedus C, Freeman H, Fratkin L, Churg A (1988) Malignant peritoneal mesothelioma after remote abdominal radiation. Cancer 61:2019–2021PubMedGoogle Scholar
  242. Gillissen A, Wiethege T (1996) Zelluläre Reaktionen der Lunge auf Mineralfasern. Pneumologie 50:5–17PubMedGoogle Scholar
  243. Hagemeijer A, Versnel MA, Van Drunen E et al. (1990) Cytogenetic analysis of malignant mesothelioma. Cancer Genet Cytogenet 47:1–28PubMedGoogle Scholar
  244. Hammar SP, Bolen JW (1988) Pleural neoplasms. In: Dail DH, Hammar SP (eds) Pulmonary pathology, 1st edn. Springer, Berlin Heidelberg New York, pp 973–1028Google Scholar
  245. Hammond EC, Selikoff IJ, Churg J (1965) Neoplasia among insulation workers in the United States with special reference to intra-abdominal neoplasia. Ann N Y Acad Sci 132:519–525PubMedGoogle Scholar
  246. Hammond EC, Selikoff IJ Scidman H (1970) Asbestos exposure, cigarette smoking and death rates. Ann N Y Acad Sci 330:473–490Google Scholar
  247. Harington JS, McGlashan ND (1998) South African asbestos: production, exports, and destinations, 1959-1993. Am J Ind Med 33:321–326Google Scholar
  248. Harvey P, Warn A, Dobbin S et al. (1998) Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology. Br J Cancer 77:1052–1059PubMedCentralPubMedGoogle Scholar
  249. Heineman EF, Bernstein L, Stark AD, Spirtas R (1996) Mesothelioma, asbestos, and reported his tory of cancer in first-degree relatives. Cancer 77:549–554PubMedGoogle Scholar
  250. Hueper WC (1964) Cancer induction by polyurethan and polysilicone plastics. J Natl Cancer Inst 33:1005–1027PubMedGoogle Scholar
  251. Huncharek M, Kelsey K, Muscat J, Christiani D (1996) Parental cancer and genetic predisposition in malignant pleural mesothelioma: a case-control study. Cancer Lett 102:205–208PubMedGoogle Scholar
  252. Huzly A (1989) Parietale Pleurektomie bei der sekundären Pleurakarzinose. Z Herz Thorax Gefäßchir 3:80–83Google Scholar
  253. Jones JS (1993) The formation and function of the mesothelioma panel of the Commission of the European Communities. Commission of the European Communities. Office for Official Publications of the European Communities, BrusselsGoogle Scholar
  254. Kallioniemi A, Kallioniemi OP, Sudar D et al. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821PubMedGoogle Scholar
  255. Karakoca Y, Emri S, Cangir AK, Baris YI (1997) Environmental pleural plaques due to asbestos and fibrous zeolite exposure in Turkey. Indoor Built Environ 6:100–105Google Scholar
  256. Katschinski HU, Müller KM (1994) Pleuramesotheliome im Raum Dresden 1964-1987. Arbeitsmed Sozialmed Umweltmed 7:284–288Google Scholar
  257. Ke Y, Reddel RR, Gerwin BI et al. (1989) Establishment of a human in vitro mesothelial cell model system for investigating mechanisms of asbestos-induced mesothelioma. Am J Pathol l34:979–991Google Scholar
  258. Kivipensas P, Bjorkqvist AM, Karhu R et al. (1996) Gains and losses of DNA sequences in malignant mesothelioma by comparative genomic hybridization. Cancer Genet Cytogenet 89:7–l3PubMedGoogle Scholar
  259. Klemperer P, Rabin CB (1931) Primary neoplasms of the pleura: a report of five cases. Arch Pathol Lab Med 11:385–412Google Scholar
  260. Knuutila S, Armengol G, Bjorkqvist AM et al. (1998) Comparative genomic hybridization study on pooled DNAs from tumors of one clinical-pathological entity. Cancer Genet Cytogenet 100:25–30PubMedGoogle Scholar
  261. König JE, Tolnay E, Wiethege T, Müller KM (2000) Co-Dexpression of vascular endothelial growth factor and its receptor flt-1 in malignant pleural mesothelioma. Respiration 67:36–40PubMedGoogle Scholar
  262. Krismann M, Wiethege T, Müller K (1999) Calretinin and p53 as markers for differentiation between reactive and neoplastic pleuralIesions? Virchows Arch 435:287Google Scholar
  263. Krismann M, Müller KM, Jaworska M, Johnen G (2000) Severe chromosomal aberrations in pleural mesotheliomas with unusual mesodermal features-comparative genomic hybridization evidence for a mesothelioma subgroup. J Mol Diag 2:209–216Google Scholar
  264. Kucharczuk JC, Randazzo B, Chang MY et al. (1997) Use of a “replication-restricted” herpes virus to treat experimental human malignant mesothelioma. Cancer Res 57:466–471PubMedGoogle Scholar
  265. Lanuti M, Gao GP, Force SD et al. (1999) Evaluation of an EIE4-deleted adenovirus expressing the herpes simplex thymidine kinase suicide gene in cancer gene therapy. Hum Gene Ther 10:463–475PubMedGoogle Scholar
  266. Lee WC, Testa JR (1999) Somatic genetic alterations in human malignant mesothelioma. Int J Oncol 14:181–188PubMedGoogle Scholar
  267. Lee WC, Balsara B, Liu Z, Jhanwar SC, Testa JR (1996) Loss of heterozygosity analysis defines a critical region in chromosome Ip22 commonly deleted in human malignant mesothelioma. Cancer Res 56:4297–4301PubMedGoogle Scholar
  268. Leers MPG, Aarts MMJ, Theunissen PHMH (1998) E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma. Histopathology 32:209–216PubMedGoogle Scholar
  269. Libbus BL, Craighead JE (1988) Chromosomal translocations with specific breakpoints in asbestos-induced rat mesotheliomas. Cancer Res 48:6455–6461PubMedGoogle Scholar
  270. Lu YY, Jhanwar SC, Cheng JQ, Testa JR (1994) Deletion mapping of the short arm of chromosome 3 in human malignant mesothelioma. Genes Chromosomes Cancer 9:76–80PubMedGoogle Scholar
  271. Lukacs KV, Porter CD, Pardo OE et al. (1999) In vivo transfer of bacterial marker genes results in differing levels of gene expression and tumor progression in immunocompetent and immunodeficient mice. Rum Gene Ther 10:2373–2379Google Scholar
  272. Mark J (1978) Monosomy 14, monosomy 22 and 13q-three chromosomal abnormalities observed in cells of two malignant mesotheliomas studied by banding techniques. Acta Cytol 22:398–401PubMedGoogle Scholar
  273. Martinis UJ, Radovic VR (1965) Pleural mesothelioma in a patient with pulmonary tuberculosis. Report of a case. Dis Chest 47:568–570PubMedGoogle Scholar
  274. Marzo AL, Fitzpatrick DR, Robinson BW, Scott B (1997) Antisense oligonucleotides specific for transforming growth factor beta2 inhibit the growth of malignant mesothelioma both in vitro and in vivo. Cancer Res 57:3200–3207PubMedGoogle Scholar
  275. Matker CM, Rizzo P, Pass HI et al. (1998) The biological activities of simian virus 40 large-T antigen and its possible oncogenic effects in humans. Monaldi Arch Chest Dis 53:193–197PubMedGoogle Scholar
  276. Maurer R, Egloff B (1975) Malignant peritoneal mesothelioma after cholangiography with thorotrast. Cancer 36: 1381–1385PubMedGoogle Scholar
  277. Maximow A (1927) über das Mesothel (Deckzellen der serösen Häute) und die Zellen der serösen Exsudate. Untersuchungen an entzündetem Gewebe und an Gewebskulturen. Arch Exp Zellforsch 4: 1–42Google Scholar
  278. McCaughey WT, McDonald AD (1977) Epidemiology of mesothelioma from estimated incidence. Prev Med 6:426–446Google Scholar
  279. McClure HM, Graham CE (1973) Malignant uterine mesotheliomas in squirrel monkeys following diethylstilbestrol administration. Lab Anim Sci 23:493–498PubMedGoogle Scholar
  280. McDonald JC (1985) Health implications of environmental exposure to asbestos. Environ Health Perspect 62:319–328PubMedCentralPubMedGoogle Scholar
  281. McDonald AD, McDonald JC (1973) Epidemiologie surveillance of mesothelioma in Canada. Can Med Assoc J 109:359–362PubMedCentralPubMedGoogle Scholar
  282. McDonald AD, McDonald JC (1980) Malignant mesothelioma in North America. Cancer 46:1650–1656PubMedGoogle Scholar
  283. Meloni AM, Stephenson CF, Li FP, Sandberg AA (1992) del(6q) as a possible primary change in malignant mesothelioma [published erratum appears in Cancer Genet Cytogenet 1992 61:110]. Cancer Genet Cytogenet 59:57-61Google Scholar
  284. Metcalf RA, Welsh JA, Bennett WP et al. (1992) p53 and Kirsten-ras mutations in human mesothelioma cell lines. Cancer Res 52:2610–2615PubMedGoogle Scholar
  285. Mor O, Yaron P, Huszar M et al. (1997) Absence of p53 mutations in malignant mesotheliomas. Am J Respir Cell Mol Biol16:9–l3PubMedGoogle Scholar
  286. Motherby H, Marcy T, Hecker M et al. (1998) Static DNA cytometry as a diagnostic aid in effusion cytology. 1. DNA aneuploidy for identification and differentiation of primary and secondary tumors of the serous membranes. Anal Quant Cytol Histol20:153–161PubMedGoogle Scholar
  287. Müller KM (1997) Mesotheliome-Pathologie/Pathogenese/ Mesotheliomregister. Pneumologie 51:335–344PubMedGoogle Scholar
  288. Mutti L, Carbone M, Giordano GG, Giordano A (1998) Simian virus 40 and human cancer. Monaldi Arch Chest Dis 53:198–201PubMedGoogle Scholar
  289. National Institute for Occupational Safety and Health (1981) Ethylene oxide: evidence of carcinogenicity. 35. NIOSH Current Intelligence Bulletin. NIOSH, Cineinnati, OHGoogle Scholar
  290. Om S, Odden S, Osnes M (1991) [Familial clustering of asbestos-related diseases]. Tidsskr N or Laegeforen 111: 1099–1101Google Scholar
  291. Orosz Z, Nagy P, Szentirmay Z, Zalatnay A, Hauser P (1999) Epithelial mesothelioma with deciduoid features. Virchows Arch 434:263–266PubMedGoogle Scholar
  292. Otte KE, Sigsgaard TI, Kjaerulff J (1990) [Massive exposure to asbestos and malignant mesothelioma, familial accumulation]. Ugeskr Laeger 152:3013–3014PubMedGoogle Scholar
  293. Pass HI, Kennedy RC, Carbone M (1996) Evidence for and implications of SV 40-like sequences in human mesotheliomas. Important Adv Oncol 1996:89–108Google Scholar
  294. Pepper C, Jasani B, Navabi H, Wynford-Thomas D, Gibbs AR (1996) Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue. Thorax 51: 1074–1076PubMedCentralPubMedGoogle Scholar
  295. Peterson JT, Greenberg SD, Buffler PA (1984) Non-asbestosrelated malignant mesothelioma. A review. Cancer 54:951–960Google Scholar
  296. Pogrebniak HW, Lubensky IA, Pass BI (1993) Differential expression of platelet derived growth factor-beta in malignant mesothelioma: a clue to future Therapics? Surg Oncol 2:235–240PubMedGoogle Scholar
  297. Popescu NC, Chahinian AP, DiPaolo JA (1988) Nonrandom chromosome alterations in human malignant mesothelioma. Cancer Res 48:142–147PubMedGoogle Scholar
  298. Prins JB, Williamson KA, Kamp MM et al. (1998) The gene for the cyclin-dependent-kinase-4 inhibitor, CDKN2A, is preferentially deleted in malignant mesothelioma. Int J Cancer 75:649–653PubMedGoogle Scholar
  299. Procopio A, Strizzi L, Giuffrida A et al. (1998) Human malignant mesothelioma of the pleura: new perspectives for diagnosis and therapy. Monaldi Arch Chest Dis 53:241–243PubMedGoogle Scholar
  300. Ribotta M, Roseo F, Salvio M et al. (1998) Recurrent chromosome 6 abnormalities in malignant mesothelioma. Monaldi Arch Chest Dis 53:228–235PubMedGoogle Scholar
  301. Riddell RH, Goodman MJ, Moossa AR (1981) Peritoneal malignant mesothelioma in a patient with recurrent peritonitis. Cancer 48:134–139PubMedGoogle Scholar
  302. Risberg B, Nickels J, Wagermark J (1980) Familial clustering of malignant mesothelioma. Cancer 45:2422–2427PubMedGoogle Scholar
  303. Rosenberg LE, Schechter A (2000) Gene therapist, heal thyself. Science 287:1757Google Scholar
  304. Sanders CL, Jackson TA (1972) Induction of mesotheliomas and sarcomas from “hot spots” of 239PuO2 activity. Health Phys 22:755–759PubMedGoogle Scholar
  305. Schoental R, Gibbard S (1972) Nasal and other tumours in rats given 3,4,5-trimethoxyeinnamaldehyde, a derivate of sinapaldehyd and of other x,b-unsaturated aldehydic wood lignin constituents. Br J Cancer 26:504–505PubMedCentralPubMedGoogle Scholar
  306. Schwarzenberger P, Harrison L, Weinacker A et al. (1998a) The treatment of malignant mesothelioma with a gene modified cancer cell line: a phase I study. Hum Gene Ther 9:2641–2649PubMedGoogle Scholar
  307. Schwarzenberger P, Harrison L, Weinacker A et al. (1998b) Gene therapy for malignant mesothelioma: a novel approach for an incurable cancer with increased incidence in Louisiana. J La State Med Soc 150:168–174PubMedGoogle Scholar
  308. Sekido Y, Pass HI, Bader S et al. (1995) Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res 55:1227–1231PubMedGoogle Scholar
  309. Shivapurkar N, Wiethege T, Wistuba II et al. (1999) Presence of simian virus 40 sequences in malignant mesotheliomas and mesothelial cell proliferations. J Cell Biochem 76: 181–188PubMedGoogle Scholar
  310. Smythe WR, Hwang HC, Amin KM et al. (1994) Use of recombinant adenovirus to transfer the herpes simplex virus thymidine kinase (HSVtk) gene to thoracic neoplasms: an effective in vitro drug sensitization system. Cancer Res 54:2055–2059PubMedGoogle Scholar
  311. Smythe WR, Hwang HC, Elshami AA, Amin KM, Albelda SM, Kaiser LR (1995) Differential sensitivity of thoracic malignant tumors to adenovirus-mediated drug sensitization gene therapy. J Thorac Cardiovasc Surg 109:626–630PubMedGoogle Scholar
  312. Solheim P, Saeter G, Finnanger AM et al. (1992) Highdose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study. Br J Cancer 65:956–960PubMedCentralPubMedGoogle Scholar
  313. Stenton SC (1997) Asbestos, Simian virus 40 and malignant mesothelioma. Thorax [Suppl 3] 52:S52–S57PubMedCentralPubMedGoogle Scholar
  314. Sterman DH, Kaiser LR, Albelda SM (1998a) Gene therapy for malignant pleural mesothelioma. Hematol Oncol Clin North Am 12:553–568PubMedGoogle Scholar
  315. Sterman DH, Treat J, Litzky LA et al. (1998b) Adenovirusmediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma. Hum Gene Ther 9:1083–1092PubMedGoogle Scholar
  316. Stewart DJ, Gertler SZ, Tomiak A et al. (1994) High dose doxorubicin plus cisplatin in the treatment of unresectable mesotheliomas: report of four cases. Lung Cancer 11:251–258PubMedGoogle Scholar
  317. Stock RJ, Fu YS, Carter JR (1979) Malignant peritoneal mesothelioma following radiotherapy for seminoma of the testis. Cancer 44:914–919PubMedGoogle Scholar
  318. Tagnon I, Blot WJ, Stroube RB et al. (1980) Mesothelioma associated with the shipbuilding industry in coastal Virginia. Cancer Res 40:3875–3879PubMedGoogle Scholar
  319. Taguchi T, Jhanwar SC, Siegfried JM, Keller SM, Testa JR (1993) Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma [published erratum appears in Cancer Res 1993 53:5063]. Cancer Res 53:4349–4355PubMedGoogle Scholar
  320. Talerman A, Montero JR, Chilcote RR (1985) Diffuse malignant peritoneal mesothelioma in a 13-year-old girl. Report of a case and review of the literature. Am J Surg Pathol 9:73–80PubMedGoogle Scholar
  321. Terao K (1978) Mesotheliomas induced by sterigmatocystin in Wistar rats. Gann 69:237–247PubMedGoogle Scholar
  322. Tiainen M, Tammilehto L, Mattson K, Knuutila S (1988) Nonrandom chromosomal abnormalities in malignant pleural mesothelioma. Cancer Genet Cytogenet 33:251–274PubMedGoogle Scholar
  323. Tiainen M, Tammilehto L, Rautonen J, Tuomi T, Mattson K, Knuutila S (1989) Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma. Br J Cancer 60:618–626PubMedCentralPubMedGoogle Scholar
  324. Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E, in collaboration with LH Sobin and pathologists from 14 countries (1999) Histological classification of lung and pleural tumours, 3rd edn. Springer, Berlin Heidelberg New YorkGoogle Scholar
  325. Treat J, Kaiser LR, Sterman DH et al. (1996) Treatment of advanced mesothelioma with the recombinant adenovirus H5.010RSVTK: a phase 1 trial (BB-IND 6274). Hum Genet Ther 7:2047–2057Google Scholar
  326. Versnel MA, Claesson-Welsh L, Hammacher A et al. (1991) Human malignant mesothelioma cell lines express PDGF beta-receptors whereas cultured normal mesothelial cells express predominantly PDGF alpha-receptors. Oncogene 6:2005–2011PubMedGoogle Scholar
  327. Wagner JC, Sleggs CA, Marchand P (1960) Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med 17:260–271PubMedCentralPubMedGoogle Scholar
  328. Walker C, Rutten F, Yuan X, Pass H, Mew DM, Everitt J (1994) Wilms’ tumor suppressor gene expression in rat and human mesothelioma. Cancer Res 54:3101–3106PubMedGoogle Scholar
  329. Wiethege T, Philips S, Müller KM (1997) Calretinin als Marker zur Differentialdiagnose von Mesotheliomen und Adenokarzinomen. Verh Dtsch Ges Pathol 81:417Google Scholar
  330. Woitowitz HJ (1987) Epidemiologie und Prävention des malignen Pleuramesothelioms. Med Klin 82:578–581Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Klaus-Michael Müller
  • Thorsten Wiethege
  • Michael Krismann
  • Klaus Junker
  • Georg Johnen

There are no affiliations available

Personalised recommendations