Identification of pathogenesis pathway in basal-like breast cancer based on mutant p53 protein and topoisomerase-IIα expression

  • Yayi Dwina Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Ria Kodariah Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Endang S.R. Hardjolukito Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta
Keywords: basal-like breast cancer, mutant p53, topoisomerase-IIα
Abstract viewed: 1033 times
PDF downloaded: 497 times

Abstract

Background: Basal-like breast cancer is difficult to treat with standard regimen therapy, because it doesn’t express hormone receptors or epidermal growth factor receptors. Identification of oncogenesis pathway is expected to find molecules which can be used as target for therapy. One candidate molecule is topoisomerase-IIα whose expression is regulated by p53. This study aimed to compare the expression of mutant p53 proteins and topoisomerase IIα in basal-like and non basal-like breast cancer, and to determine the association between mutant p53 proteins and topoisomerase IIα in basal-like group.

Methods: The samples were 40 formalin fixed paraffin embedded tissues from verified triple negative breast cancer tissue. The samples were divided into 2 groups, basal-like and non basal-like breast cancer, based on cytokeratin - 5 (CK-5) expression. Mutant p53 proteins and topoisomerase IIα were stained using immunohistochemistry method, scored and compared. Statistical test used SPSS software version 16 for descriptive statistics, kappa test, normality test, comparison of two mean, and categorical comparison.

Results: Median (min-max) of mutant p53 protein expression in basal-like group was 21 (0-100), the non basal-like group was 2 (0-80), p = 0.061. Min-max of topoisomerase IIα in basal-like group was 263 (15-492), non basal-like group was 262 (0-481), p = 0.409. There was an association between mutant p53 positivity with breast cancer subtype (p = 0.027) and between mutant p53-topoisomerase IIα coexpression with breast cancer subtype (p = 0.018).

Conclusion: Co-expression of mutant p53 with topoisomerase IIα has the role in one of the pathway of basal-like breast cancer pathogenesis.

References

  1. World Health Organization [Internet]. Breast cancer: prevention and control. Breast cancer. [updated 2008; cited 2010 Dec 20]. Available from: http://www.who.int/cancer/detection/breastcancer/en/

  2. Rakha E, Reis-Filho JS. Basal like breast carcinoma from expression profiling to routine practice. Arch Pathol Lab Med.2009;133(6):860-8. http://.dx.doi: 10.1200/JCO.2007.13.1748

  3. Lester SC. The breast. In: Kumar V, Abbas AK, Fausto N, Aster JC, editors. Robbins and Cotran pathologic basis of disease. 8th ed. Philadelphia, PA: Sauders Elseviers; 2010. p. 1065-96. http://dx.doi.org/10.1016/B978-1-4377-0792-2.50028-6

  4. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-52. http://dx.doi.org/10.1038/35021093

  5. Rakha E, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008;26(15):2568-81. http://dx.doi.org/10.1200/JCO.2007.13.1748

  6. Holstege H, Joosse SA, van Oostrom CT, Nederlof PM, de Vries A, Jonkers J. High Incidence of protein truncating TP53 mutations in BRCA-1 related breast cancer. Cancer Res. 2009;69(8):3625-33. http://dx.doi.org/10.1158/0008-5472.CAN-08-3426

  7. Wang Q, Zambetti GP, Suttle DP. Inhibition of DNA topoisomerase IIα gene expression by the p53 tumor suppressor. Mol Cell Biol. 1997;17(1):389-97.

  8. Sandri MI, Isaacs RJ, Ongkeko WM, Harris AL, Hickson ID, Broggini M, et al. p53 regulates the minimal promoter of the human topoisomerase IIα gene. Nucleic Acids Res.1996;24(22):4464-70. http://dx.doi.org/10.1093/nar/24.22.4464

  9. Roca J. Survey and summary topoisomerase II: a fitted mechanism for the chromatin landscape. Nucleic Acid Res.2009;37(3):721-30. http://dx.doi.org/10.1093/nar/gkn994

  10. Nitiss JL. DNA topoisomerase II and its growing repertoire of biological function. Nat Rev Cancer. 2009;9(5):327-37. http://dx.doi.org/10.1038/nrc2608

  11. Hellemans P, van Dam PA, Geyskens M, van Oosterom AT, Buytaert P, Van Marck E. Immunohistochemical study of topoisomerase II-α ekspression in primary ductal carcinoma of the breast. J Clin Pathol.1995;48(2):147-50. http://dx.doi.org/10.1136/jcp.48.2.147

  12. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869-74. http://dx.doi.org/10.1073/pnas.191367098

  13. Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer. 2009;9(5):338-50. http://dx.doi.org/10.1038/nrc2607

  14. Dogu GG, Ozkan M, Ozturk F, Dikilitas M, Er O, Ozturk A. Triple-negative breast cancer: immunohistochemical correlation with basaloid markers and prognostic value of survivin. Med Oncol.2010;27(1):34-9. http://dx.doi.org/10.1007/s12032-009-9166-3

  15. Lukas J, Niu N, Press MF. p53 mutations and expression in breast carcinoma in situ. Am J Pathol.2000;156(1):183-91. http://dx.doi.org/10.1016/S0002-9440(10)64718-9

  16. Conforti R, Boulet T, Tomasic G, Spielmann M, Delaloge S, Arriagada R, et al. Predictive value of MRP2, p53, bcl2 and topoisomerase II immunostainings for the efficacy of anthracyclines-based adjuvant chemotherapy in breast cancer: Results from two randomized trials. J Clin Oncol (Meeting Abstracts). 2008;26(15 Suppl):616.

  17. Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene. 2007;26(14):2126-32. http://dx.doi.org/10.1038/sj.onc.1210014

  18. Ahmed M, Lalloo F, Evans DG. Update on genetic predisposition to breast cancer. Expert Rev Anticancer Ther. 2009;9(8):1103-13. http://dx.doi.org/10.1586/era.09.38

  19. Romero A, Martín M, Cheang MC, López García-Asenjo JA, Oliva B, He X, et al. Assessment of topoisomerase II α status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization. Am J Pathol.2011:178(4):1453-60. http://dx.doi.org/10.1016/j.ajpath.2010.12.042

  20. Woessner RD, Mattern MR, Mirabelli CK, Jhonson RK, Drake FH. Proliferation- and cell cyle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. Cell Growth Differ.1991;2(4):209-14.

  21. N, Triaspolitica. "Kanker Payudara: Informasi, Penyebab, Gejala, Stadium Dan Pengobatan." Mau Nanya Dong Dok. N.p, 28 June 2017. Web. 30 June 2017. <https://nanyadongdok.blogspot.com/2017/06/kanker-payudara-informasi-penyebab.html>.

  22. Vojtĕsek B, Bártek J, Midgley CA, Lane DP. An immunochemical analysis of the human nuclear phosphoprotein p53 new monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods.1992:151(1-2):237-44. http://dx.doi.org/10.1016/0022-1759(92)90122-A

  23. Cooper K, Haffajee Z. bcl-2 and p53 protein expression in follicular lymphoma. J Pathol. 1997;182(3):307-10. http://dx.doi.org/10.1002/(SICI)1096-9896(199707)182:3<307::AID-PATH873>3.0.CO;2-6

  24. Sjögren S1, Inganäs M, Norberg T, Lindgren A, Nordgren H, Holmberg L, et al. The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry. J Natl Cancer Inst.1996;88(3-4):173-82. http://dx.doi.org/10.1093/jnci/88.3-4.173

  25. Varna M, Bousquet G, Plassa LF, Bertheau P, Janin A. TP53 status and response to treatment in breast cancers. J Biomed Biotech.2011;1-9. http://dx.doi.org/10.1155/2011/284584

Published
2015-01-27
How to Cite
1.
Dwina Y, Kodariah R, Hardjolukito ES. Identification of pathogenesis pathway in basal-like breast cancer based on mutant p53 protein and topoisomerase-IIα expression. Med J Indones [Internet]. 2015Jan.27 [cited 2019Dec.15];23(4):197-02. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/995
Section
Basic Medical Research