Virchows Archiv

, Volume 427, Issue 4, pp 431–436 | Cite as

Immunoreactivity for p53 and mdm2 and the detection of p53 mutations in human malignant mesothelioma

  • K. Segers
  • S. K. Singh
  • M. Ramael
  • E. Van Marck
  • H. Backhovens
  • J. De Voecht
  • C. Van Broeckhoven
Original Article


Previous immunohistochemical studies on malignant mesothelioma with antibodies recognizing both the wild and the mutant types of the p53 protein have shown immunoreactivity in 25–70% of cases. This study was designed to determine whether there is immunoreactivity for p53 and mdm2 protein in malignant mesothelioma and to correlate p53 expression with the detection of mutations in p53 at DNA level. In 10 of 15 cases there was immunoreactivity for p53. In 6 of these cases immunoreactivity for mdm2 was also detected. In one p53-immunonegative case, a mutation of the p53 gene resulting in a stop codon was found. These results suggest that mdm2 might be involved in the inhibition of p53 in malignant mesothelioma. Also, these data suggest the existence of other proteins than mdm2 that may associate with p53.

Key words

Malignant mesothelioma p53 mdm2 Automated sequencing 


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  1. 1.
    Barnes DM, Hanby AM, Gillet CE, Mohammed S, Hodgson S, Bobrow LG, Leigh IM, Purkis T, MacGeoch C, Spurr NK, Bartek J, Vojtesek B, Picksley SM, Lane DP (1992) Abnormal expression of wild type p53 protein in normal cells of a cancer family patient. Lancet 340:259–263Google Scholar
  2. 2.
    Battifora H (1994) p53 immunohistochemistry: a word of caution. Hum Pathol 25:435–437Google Scholar
  3. 3.
    Blin N, Stafford DM (1976) A general method for the isolation of high molecular-weight DNA from eukaryotes. Nucleic Acids Res 3:2303–2308Google Scholar
  4. 4.
    Cagle PT, Brown RW, Lebowitz RM (1994) p53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens. Hum Pathol 25:443–448Google Scholar
  5. 5.
    Callahan R, Cropp CS, Merlo GR, Liscia DS, Cappa AP, Lidereau R (1992) Somatic mutations and human breast cancer. A status report. Cancer 69 [Suppl]:1582–1588Google Scholar
  6. 6.
    Chang F, Syrjänen S, Tervahauta A, Syrjänen K (1993) Tumorigenesis associated with the p53 tumour suppressor gene. Br J Cancer 68:653–661Google Scholar
  7. 7.
    Ciechanover A, DiGiuseppe JA, Bercovich B, Orian A, Richter JD, Schwartz A, Brodeur GM (1991) Degradiation of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci USA 88:139–143Google Scholar
  8. 8.
    Cordon-Cardo C, Latres E, Drobnjak M, Oliva MR, Pollack D, Woodruff JM, Marechal V, Chen J, Brennan FM, Levine AJ (1994) Molecular abnormalities of mdm2 and p53 genes in adult soft tissue carcinoma. Cancer Res 54:794–799Google Scholar
  9. 9.
    Cote RJ, Jhanwar SC, Novick S, Pellicer A (1991) Genetic alterations of the p53 gene are a feature of malignant mesotheliomas. Cancer Res 51:5410–5416Google Scholar
  10. 10.
    DePangher Manzini V, Brollo A, Franceschi S, De Matthaeis M, Talamini R, Bianchi C (1993) Prognostic factors of malignant mesothelioma of the pleura. Cancer 72:410–417Google Scholar
  11. 11.
    Dobashi Y, Sugimura H, Sakamoto A, Mernyei M, Mori M, Oyama T, Machinami R (1994) Stepwise participation of p53 gene mutation during dedifferentiation of human thyroid carcinomas. Diagn Mol Pathol 3:9–14Google Scholar
  12. 12.
    Hall PA, Lane PL (1994) p53 in tumour pathology: can we trust immunohistochemistry?-revisited! J Pathol (Lond) 172:1–4Google Scholar
  13. 13.
    Henderson DW, Shilin KB, Whitaker D, Atwood HD, Constance TJ, Steele RH, Leppard PJ (1992) The pathology of malignant mesothelioma, including immunohistology and ultrastructure. In: Henderson DW, Shilkin KB, Le P. Langlois S, Whitaker D (eds) Malignant mesothelioma. Hemisphere, New York Washington Philadelphia London, pp 69–139Google Scholar
  14. 14.
    Kafiri G, Thomas DM, Shephard NA, Krausz T, Lane DP, Hall PA (1992) p53 expression is common in malignant mesothelioma. Histopathology 21:331–334Google Scholar
  15. 15.
    Lamb P, Crawford L (1986) Characterization of the human p53 gene. Mol Cell Biol 8:1379–1385Google Scholar
  16. 16.
    Leach FS, Tokino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW, Vogelstein B (1993) p53 mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res 53:2231–2234Google Scholar
  17. 17.
    MacBride O, Merry D, Givol D (1986) The gene for human p53 cellular tumour antigen is located on chromosome 17 short arm (17p13). Proc Natl Acad Sci USA 83:130–134Google Scholar
  18. 18.
    Mayall FG, Goddard, Gibbs AR (1992) p53 immunostaining in the distinction between benign and malignant mesothelial proliferations using formalin-fixed paraffin sections. J Pathol (Lond) 168:377–381Google Scholar
  19. 19.
    Mazars G-R, Jeanteur P, Lynch HT, Lenoir G, Theillet C (1992) Nucleotide sequence polymorphism in a hotspot mutation region of the p53 gene. Oncogene 8:781–782Google Scholar
  20. 20.
    Metcalf RA, Welsh JA, Bennet WP, Seddon MB, Lehman TA, Pelin K, Linnainmaa K, Tammilehto L, Mattson K, Gerwin BI, Harris CC (1992) p53 and Kirsten-ras mutations in human mesothelioma cell lines. Cancer Res 52:2610–2615Google Scholar
  21. 21.
    Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D'Amico D, Bodner S, Oie HK, Linnoila RI, Mulshine JL, Minna JD, Gazdar AF (1992) p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene 7:171–180Google Scholar
  22. 22.
    Molès J-P, Moyret C, Guillot B, Jeanteur P, Guilhou J-J, Theillet C, Basset-Séguin N (1993) p53 gene mutations in epithelial skin cancers. Oncogene 8:583–588Google Scholar
  23. 23.
    Mossman BT, Bignon J, Corn M, Seaton A, Gee JB (1990) Asbestos: scientific developments and implications for public policy. Science 247:294–301PubMedGoogle Scholar
  24. 24.
    Murakami Y, Hayashi K, Sekiya T (1991) Detection of aberrations of the p53 alleles and the gene transcript in human tumour cell lines by single-strand conformation polymorphism analysis. Cancer Res 51:3356–3361Google Scholar
  25. 25.
    Murakami Y, Hayashi K, Hirohashi S, Sekiya T (1991) Aberrations of the tumour suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res 51:5520–5525Google Scholar
  26. 26.
    Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80–83Google Scholar
  27. 27.
    Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362:857–860Google Scholar
  28. 28.
    Ramael M, Lemmens G, Eerdekens C, Buysse C, Deblier I, Jacobs W, VanMarck E (1992) Immunoreactivity for p53 protein in malignant mesothelioma and non-neoplastic mesothelium. J Pathol (Lond) 168:371–375Google Scholar
  29. 29.
    Romano JW, Ehrhart JC, Duthu A, Kim CM, Appela E, May P (1989) Identification and characterization of a p53 mutation in a human osteosarcoma cell line. Oncogene 4:1483–1488Google Scholar
  30. 30.
    Ronen D, Rotter V, Reisman D (1991) Expression from the murine p53 promoter is mediated by factor binding to a down-stream helix-loop-helix recognition motif. Proc Natl Acad Sci USA 88:4128–4132Google Scholar
  31. 31.
    Sakai E, Tsuchida N (1992) Most human squamous cell carcinomas in the oral cavity contain mutated p53 tumour-suppressor genes. Oncogene 7:927–933Google Scholar
  32. 32.
    Shaw P, Tardy S, Benito E, Obrador A, Costa J (1991) Occurrence of Ki-ras and p53 mutations in primary colorectal tumours. Oncogene 6:2121–2128Google Scholar
  33. 33.
    Vogelstein B, Kinzler KW (1992) p53 function and dysfunction. Cell 70:523–526Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • K. Segers
    • 1
  • S. K. Singh
    • 1
  • M. Ramael
    • 1
  • E. Van Marck
    • 1
  • H. Backhovens
    • 2
  • J. De Voecht
    • 2
  • C. Van Broeckhoven
    • 2
  1. 1.Department of MedicineLaboratory of Pathology, University of Antwerp (UIA)AntwerpenBelgium
  2. 2.Department of BiochemistryLaboratory of Neurogenetics, Born Bunge Foundation, University of Antwerp (UIA)AntwerpenBelgium

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