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TP53 alterations in atypical ductal hyperplasia and ductal carcinomain situ of the breast

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Summary

Abnormalities in theTP53 tumour suppressor gene in 75 atypical ductal hyperplasias and 62 ductalcarcinomasin situ (DCIS) of the breast were studied using immunohistochemistry and mutation analysis. Accumulation of p53 protein was detected in 10 out of 62 (16%) DCIS, whereas no cases of positive staining was observed in the atypical lesions.TP53 mutations were identified in four out of 30 (13%) DCIS by constant denaturant gel electrophoresis (CDGE). Two of these cases were positive and two negative for p53 protein. A total of 12 out of 62 DCIS (19%) carriedTP53 mutation and/or p53 protein overexpression. The present results suggest thatTP53 alterations may be important in the development of a subset of DCIS.

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References

  1. Levine AJ, Momand J, Finlay CA: The p53 tumour suppressor gene. Nature 351: 453–456, 1993

    Google Scholar 

  2. Donehower LA, Bradley A: The tumor suppressor p53. Biochim Biophys Acta 1155: 181–205, 1993

    PubMed  Google Scholar 

  3. Harris CC, Hollstein M: Clinical implications of the p53 tumour suppressor gene. N Engl J Med 329: 1318–1327, 1993

    PubMed  Google Scholar 

  4. Hollstein M, Risce K, Greenblatt MS, Soussi T, Fuchs R, Sørli T, Hovig E, Smith-Sørensen B, Montesano R, Harris CC: Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acid Res 22: 3551–3555, 1994

    PubMed  Google Scholar 

  5. Finlay CA, Himnds PW, Tan TH: Activating mutations for transformation by p53 produce a gene product that forms an fsc 70-p53 complex with an altered half-life. Mol Cell Biol 8: 531–539, 1988

    PubMed  Google Scholar 

  6. Gronstajaski RM, Goldberg AL, Pardee AB: Energy requirement for degradation of tumour-associated protein p53. Mol Cell Biol 4: 442–448, 1984

    PubMed  Google Scholar 

  7. Lane D: The regulation of p53 function: Steiner award lecture. Int J Cancer 57: 623–627, 1994

    PubMed  Google Scholar 

  8. Momand J, Zambetti GP, Olson DC, George D, Levine AJ: The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237–1245, 1992

    PubMed  Google Scholar 

  9. Bàrtek J, Bàrtkovà J, Vojtesek B, Staskovà Z, Rejthar A, Kovarik J, Lane DP: Patterns of expression of the p53 tumor suppressor in human breast tissues and tumorsin situ andin vitro. Int J Cancer 46: 839–844, 1990

    PubMed  Google Scholar 

  10. Davidoff AM, Kerns BM, Pence JC, Marks JR, Iglehart DJ: p53 alterations in all stages of breast cancer. J Surg Onc 48: 260–267, 1991

    PubMed  Google Scholar 

  11. Walker RA, Dearing SJ, Lane DP, Varley JM: Expression of p53 protein in infiltrating andin situ breast carcinomas. J Pathol 165: 203–211, 1991

    PubMed  Google Scholar 

  12. Thor AD, Moore DH, Edgerton SM, Kawasaki ES, Reishaus E, Lynch HT, Marcus JN, Schwartz L, Chen L, Mayall BH, Smith HS: Accumulation of p53 tumour suppressor gene protein: An independent marker of prognosis in breast cancers. J Natl Cancer Inst 84: 845–855, 1992

    PubMed  Google Scholar 

  13. Poller DN, Hutchins CE, Galea M: p53 protein expression in breast carcinoma: Relationship to expression of epidermal growth factor receptor, c-erb 2 protein overexpression, and oestrogen receptor. Br J Cancer 66: 583–588, 1992

    PubMed  Google Scholar 

  14. Poller DN, Roberts EC, Bell JA, Elston CW, Blamey RW, Ellis IO: p53 protein expression in mammary ductal carcinomain situ. Relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein. J Pathol 24: 463–468, 1993

    Google Scholar 

  15. Tsuda H, Iwya K, Fukutomi T, Hirohashi S: p53 mutations and c-erbB-2 amplification in intraductal and invasive breast carcinoma of high histologic grade. Jpn J Cancer Res 84: 394–401, 1993

    PubMed  Google Scholar 

  16. Bhargava V, Thor A, Deng G, Ljung B-M, Moore L, Waldman F, Benz C, Goodson W, Mayall B, Chew K, Smith HS: The association of p53 immunopositivity with tumor proliferation and other prognostic indicators in breast cancer. Mod Pathol 7: 361–368, 1994

    PubMed  Google Scholar 

  17. O'Malley FP, Unencak Jones CL, Dupont WD, Parl F, Mannings S, Page DL: p53 mutations are confined to the comedo type ductal carcinomain situ of the breast. Immunohistochemical and sequencing data. Lab Invest 71: 67–72, 1994

    PubMed  Google Scholar 

  18. Zafrani B, Leroyer A, Fourquel A, Laurent M, Trophilme D, Validire P, Sastre Garau X: Mammographically detected ductalin situ carcinoma of the breast analyzed with a new classification. A study of 127 cases: correlation with estrogen and progesterone receptors, p53 and c-erbB-2 protein, and proliferation activity. Semin Diagn Pathol 11: 208–214, 1994

    PubMed  Google Scholar 

  19. Coles C, Condie A, Chetty U, Steel M, Evans HJ, Prosser J: p53 mutations in breast cancer. Cancer Res 52: 5291–5298, 1992

    PubMed  Google Scholar 

  20. Thompson AM, Anderson TJ, Condie A, Prosser J, Chetty U, Carter DC, Evans HJ, Steel CM: p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters. Int J Cancer 50: 528–532, 1992

    PubMed  Google Scholar 

  21. Andersen TI, Holm R, Nesland JM, Heimdal KR, Ottestad L, Børresen A-L: Prognostic significance ofTP53 in breast carcinoma. Br J Cancer 68: 560–548, 1993

    Google Scholar 

  22. Lipponen P, Aaltomaa HJ, Syrjänen S: p53 protein expression in breast cancer as related to histopathological characteristics and prognosis. Int J Cancer 55: 51–56, 1993

    PubMed  Google Scholar 

  23. Thorlacius S, Børresen A-L, Eyfjord JE: Somatic p53 mutations in human breast carcinomas in an Icelandic population: A prognostic factor. Cancer Res 53: 1637–1641, 1993

    PubMed  Google Scholar 

  24. Azzopardi JG: Problems in breast pathology. In: Bennington JL (ed.) Major Problems in Pathology. W.B. Saunders Company Ltd, London, Philadelphia, Toronto, 1979, Vol 11

    Google Scholar 

  25. Holland R, Peterse L, Millis RR, Eusebi V, Faverly D, van de Vijver MJ, Zafrani B: Ductal carcinomain situ: A proposal for a new classification. Seminars in Diagnostic Pathology. Ductal CarcinomaIn situ. W.B. Saunders Company Ltd, Philadelphia, 1994, Vol 11, pp 167–180

    Google Scholar 

  26. Mies C, Hauldsworth J, Chaganti RSK: Extraction of DNA from paraffin blocks for Southern blot analysis. Am J Surg Pathol 15(2): 169–174, 1991

    PubMed  Google Scholar 

  27. Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW Jr, Rary JM: Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74: 1245–1249, 1977

    PubMed  Google Scholar 

  28. Børresen A-L, Hovig E, Smith-Sørensen B, Malkin D, Lystad S, Andersen TI, Nesland JM, Isselbacher KJ, Friend SH: Constant Denaturant Gel Electrophoresis as a rapid screening technique for p53 mutations. Proc Natl Acad Sci USA 88: 8405–8409, 1991

    PubMed  Google Scholar 

  29. Condie C, Eeles R, Børresen A-L, Coles C, Cooper C, Prosser J: Detection of point mutations in the p53 gene: comparison of single-strand conformation polymorphism, constant denaturant gel electrophoresis, and hydroxylamine and osmium tetroxide techniques. Human Mutation 2: 58–66, 1993

    PubMed  Google Scholar 

  30. Andersen TI, Børresen A-L: Alterations of theTP53 gene as potential molecular marker in breast carcinomas; advantages of using CDGE in mutation detection. Diagn Molec Pathol (In press)

  31. Hsu SM, Raine L, Fanger H: A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptides hormones with radioimmunoassay antibodies. Am J Clin Pathol 75: 734–738, 1981

    PubMed  Google Scholar 

  32. Bobrow LG, Happerfield LC, Gregory WM, Springall RD, Millis R: The classification of ductal carcinomain situ and its association with biological markers. In: Santa Cruz DJ (ed.) Seminars in Diagnostic Pathology. Ductal CarcinomaIn situ. W.B. Saunders Company Ltd, Philadelphia, 1994, Vol 11, pp 199–207

    Google Scholar 

  33. Holm R, Skomedal H, Helland Å, Kristensen G, Børresen A-L, Nesland JM: Immunochemical analysis of p53 protein overexpression in normal, premalignant, and malignant tissues of the cervix uteri. J Pathol 169: 21–26, 1993

    PubMed  Google Scholar 

  34. Holm R, Abeler VM, Skomedal H, Nesland JM: Overexpression of p53 protein and c-erb-2 protein in small cell carcinoma of the cervix uteri. Zentralbl Pathol 139: 153–156, 1993

    PubMed  Google Scholar 

  35. Purdie CA, O'Grady J, Piris J, Wyllie AH, Bird CC: p53 expression in colorectal tumors. Am J Pathol 138: 807–812, 1991

    PubMed  Google Scholar 

  36. Børresen A-L, Andersen TI, Eyfjörd JE, Corneli RS, Thorlacius S, Borg Å, Johansson U, Theillet C, Scherneck S, Hartmann S, Cornelisse CJ, Hovig E, Devilee P:TP53 mutations and breast cancer prognosis: particularly poor survival rates for cases with mutations in zinc-binding domains. Genes Chrom Cancer 14: 71–75, 1995

    PubMed  Google Scholar 

  37. Hall AP, Mackee PH, Menage HP, Dover R, Lane DP: High levels of p53 protein in UV-irradiated normal skin. Oncogene 8: 203–207, 1993

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, The Norwegian Radium Hospital and Institute for Cancer Research, N-0310, Oslo, Norway

    Margaret Chitemerere, Ruth Holm, Frank Karlsen & Jahn Marthin Nesland

  2. Department of Genetics, The Norwegian Radium Hospital and Institute for Cancer Research, N-0310, Oslo, Norway

    Tone Ikdahl Andersen & Anne-Lise Børresen

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  1. Margaret Chitemerere
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Chitemerere, M., Andersen, T.I., Holm, R. et al. TP53 alterations in atypical ductal hyperplasia and ductal carcinomain situ of the breast. Breast Cancer Res Tr 41, 103–109 (1996). https://doi.org/10.1007/BF01807155

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