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Journal of Cancer Research and Clinical Oncology

, Volume 122, Issue 8, pp 489–494 | Cite as

Immunostaining of p53 protein in ovarian carcinoma: correlation with histopathological data and clinical outcome

  • Angela Reles
  • Annette Schmider
  • Michael F. Press
  • Ines Schönborn
  • Wolfgang Friedmann
  • S. Huber-Schumacher
  • Torsten Strohmeyer
  • Werner Lichtenegger
Original Paper Clinical Oncology

Abstract

Objective: The objective of this study was to analyze the incidence of immunohistochemically detectable p53 protein accumulation in epithelial ovarian carcinomas and to correlate these data with the clinical outcome so as to clarify further the role of p53 mutations in prognosis with these patients.Methods: Tumor tissues from 179 patients with epithelial ovarian carcinoma were used for immuno-histochemical analysis with monoclonal antibody DO1 and BP 53-12-1 on formalin-fixed, paraffin-embedded tissue.Results: A total of 78 cases (44%) showed positive nuclear p53 staining. The p53-positive cases were found in all histological types of epithelial ovarian tumors. p53 staining was found in tumors of all stages with a higher percentage of positive cases in stage IV ovarian carcinomas (not significant). Poorly differentiated carcinomas showed a significantly higher percentage of p53 protein expression than did highly differentiated tumors (P=0.0002). Clinical follow-up of up to 14 years (median 25 months) showed a slightly but not significantly shortened disease-free and overall survival time for patients with p53-positive epithelial ovarian carcinomas.Conclusions: We conclude from our data that p53 expression in ovarian carcinoma is associated with poor differentiation but not with the disease being in an advanced stage. There was a tendency for shortened disease-free and overall survival for patients with p53-positive tumors.

Key words

p53 Tumor-suppressor gene Ovarian carcinoma Immunohistochemistry 

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References

  1. Banks L, Matlashewski G, Crawford L (1986) Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem 159:529–534Google Scholar
  2. Bartek J, Bartkova J, Vojtesek B, Staskova Z, Lukas J, Rejthar A, Kovarik J, Midgley CA, Gannon JV, Lane DP (1991) Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene 6:1699–1703Google Scholar
  3. Berchuck A, Kohler MF, Marks JR, Wiseman R, Boyd J, Bast RC (1994) The p53 tumor suppressor gene frequently is altered in gynecologic cancers. Am J Obstet Gynecol 170:246–252Google Scholar
  4. Casey G, Lo-Hsueh M, Lopez ME, Vogelstein B, Stanbridge EJ (1991) Growth suppression of human breast cancer cells by the introduction of a wild-type p53 gene. Oncogene 6:1791–1797Google Scholar
  5. Day TG, Gallager HS, Rutledge FN (1975) Epithelial carcinoma of the ovary: Prognostic importance of histological grade. Natl Cancer Inst Monogr 42:15–18Google Scholar
  6. Eccles DM, Brett L, Lessells A, Gruber L, Lane D, Steel CM, Leonard RCF (1992) Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma. Br J Cancer 65:40–44Google Scholar
  7. El Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B (1992) Definition of a consensus binding site for p53. Nat Genet 1:45–49Google Scholar
  8. Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, and Levine J (1988) Activating mutations for transformation by p53 produce a gene product that forms and hsc70-p53 complex with an altered half-life. Mol Cell Biol 8:531–539Google Scholar
  9. Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093Google Scholar
  10. Fisher CJ, Gillett CE, Vojtesek B, Barnes DM, Millis RR (1994) Problems with p53 immunohistochemical staining: the effect of fixation and variation in the methods of evaluation. Br J Cancer 69:26–31Google Scholar
  11. Funk WD, Pak DT, Karas RH, Wright WE, Shay JW (1992) A transcriptionally active DNA-binding site for human p53. Mol Cell Biol 12:2866–2871Google Scholar
  12. Halevy O, Michalovitz D, Oren M (1990) Different tumor-derived p53 mutants exhibit distinct biological activities. Science 250:113–116Google Scholar
  13. Hall PA, McKee PH, Menage HduP, Dover R, Lane DP (1993) High levels of p53 protein in UV-irradiated normal human skin. Oncogene 8:203–207Google Scholar
  14. Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329:1318–1327Google Scholar
  15. Hartmann LC, Podratz KC, Keeney GL, Kamel NA, Edmonson JH, Grill JP, Su JQ, Katzmann JA, Roche PC (1994) Prognostic significance of p53 immunostaining in epithelial ovarian cancer. J Clin Oncol 12:64–69Google Scholar
  16. Hinds PW, Weinberg RA (1994) Tumor suppressor genes. Curr Opinion Genet Dev 4:135–141Google Scholar
  17. Hinds P, Finlay C, Levine A (1989) Mutation is required to activate the p53 gene for cooperation with theras oncogene and transformation. J Virol 63:739–746Google Scholar
  18. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 Mutations in human cancers. Science 253:49–53Google Scholar
  19. Kastan MB, Onyinye O, Sidransky D, Vogelstein B, Craig R (1991) Participation of p53 in the cellular response to DNA damage. Cancer Res 51:6304–6311Google Scholar
  20. Kihana T, Tsuda H, Teshima S, Okada S, Matsuura S, Hirohashi S (1992) High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumor DNA aneuploidy. Jpn J Cancer Res 83:978–984Google Scholar
  21. Kohler MF, Kerns BJM, Humphrey PA, Marks JR, Bast RC, Berchuck A (1993) Mutation and overexpression of p53 in early stage ovarian cancer. Obstet Gynecol 5:643–650Google Scholar
  22. Kraiss S, Spiess S, Reihsaus E, Montenarh M (1991) Correlation of metabolic stability and altered quaternary structure of oncoprotein p53 with cell transformation. Exp Cell Res 192:157–164Google Scholar
  23. Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB (1992) Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 89:7491–7495Google Scholar
  24. Kupryjanczyk J, Thor AD, Beauchamp R, Merrit V, Edgerton SM, Bell DA, Yandell DW (1993) p53 gene mutations and protein accumulation in human ovarian cancer. Proc Natl Acad Sci USA 90:4961–4965Google Scholar
  25. Kupryjanczyk J, Bell DA, Yandell DW, Scully RE, Thor AD (1994) p53 expression in ovarian borderline tumors and stage I carcinomas. Am J Clin Pathol 102:671–676Google Scholar
  26. Lee ET (1980) Statistical methods for survival data analysis. Lifetime Learning, Belmont, CalifGoogle Scholar
  27. Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456Google Scholar
  28. Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, Pence JC, Dodge RK, Clarke-Pearson DL (1991) Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 51:2979–2984Google Scholar
  29. Mazars R, Pujol P, Maudelonde T, Jeanteur P, Theillet C (1991) p53 mutations in ovarian cancer: a late event? Oncogene 6:1685–1690Google Scholar
  30. Miller C, Mohanadas T, Wolf D, Prokocimer M, Rotter V, Koeffler HP (1986) Human p53 gene localized to short arm of chromosome 17. Nature 319:783–784Google Scholar
  31. Milner BJ, Allan LA, Eccles DM, Kitchener HC, Leonard RCF, Kelly KF, Parkin DE, Haites NE (1993) p53 mutation is a common genetic event in ovarian carcinoma. Cancer Res 53:2128–2132Google Scholar
  32. Naito M, Satake M, Sakai E, Hirano Y, Tsuchida N, Kanzaki H, Ito Y, Mori T (1992) Detection of p53 gene mutations in human ovarian and endometrial cancers by polymerase chain reaction-single strand conformation polymorphism analysis. Jpn J Cancer Res 83:1030–1036Google Scholar
  33. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708Google Scholar
  34. Rasbridge SA, Gillett CE, Seymour A-M, Millis RR (1993) The effect of chemotherapy on histological and biological features of breast carcinoma. J Pathol 169 [Suppl]:191Google Scholar
  35. Soussi T, Caron de Fromentel C, May P (1990) Structural aspects of the p53 protein in relation to gene evolution. Oncogene 5:945–952Google Scholar
  36. Thor AD, Moore DH, Edgerton SM, Kawasaki ES, Reihsaus E, Lynch HT, Marcus JN, Schwartz L, Chen LC, Mayall BH, Smith HS (1992) Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J National Cancer Inst 84:845–855Google Scholar
  37. Vogelstein B, Kinzler KW (1992) p53 function and dysfunction. Cell 70:523–526Google Scholar
  38. Vojtesek B, Bártek J, Midgley CA, Lane DP (1992) An immunochemical analysis of the human nuclear phosphoprotein p53. J Immunol Methods 151:237–244Google Scholar
  39. Younish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimichi A, Oren M (1991) Wild-type p53 induces apoptosis of myeloid leukemic cells that is inhibited by interleukin-6. Nature 352:345–347Google Scholar
  40. Zambetti GP, Bargonetti J, Walker K, Prives C, Levine AJ (1992) Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element. Genes Dev 6:1143–1152Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Angela Reles
    • 1
  • Annette Schmider
    • 1
  • Michael F. Press
    • 2
  • Ines Schönborn
    • 1
  • Wolfgang Friedmann
    • 1
  • S. Huber-Schumacher
    • 1
  • Torsten Strohmeyer
    • 3
  • Werner Lichtenegger
    • 1
  1. 1.Department of Gynecology and Obstetrics, Virchow-KlinikumHumboldt-UniversityBerlinGermany
  2. 2.Department of PathologyUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of OncologySchering AGBerlinGermany

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