Skip to main content

Advertisement

SpringerLink
Log in

Bcl-2 expression and triple negative profile in breast carcinoma

  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Many biomarkers for breast cancer prognosis have been proposed during the last two decades, among which HER2 and oestrogen receptors are of common use in routine clinical practice. However, in recent years, BCL2 has been recognized as an important prognostic parameter in human breast cancer, although its clinical utility is well established. The aim of this study was to examine the protein expression patterns of BCL2, HER2, oestrogen (ER) and progesterone receptors (PR) and to evaluate their correlation with survival and other prognostic parameters such as tumour size, histological grade and metastasis. We used a retrospective study including 84 Tunisian women with breast cancer. Immunohistochemistry was used to measure protein expression levels of several biomarkers. Association with conventional biopathological factors was analysed by SPSS (version13). The expression rates of BCL2, HER2, ER and PR were, respectively, 69, 62, 58.3 and 51.2%. In univariate analyses, BCL2 was highly correlated with both PR (P < 0.001) and ER (P = 0.006) and also with HER2 expression (P = 0.001). The triple negative profile showed a significant association with SBR (P = 0.016) and BCL2 expression (P = 0.02). In multivariate analyses, a significant association was maintained between BCL2 and both PR and ER (P = 0.02 and P = 0.004, respectively). Survival analysis showed that BCL2 expression was positively correlated with patients survival (P = 0.032). A Bayesian network analysis of all the variables confirmed the high value of BCL2 expression as a predictor of survival. As conclusion, BCL2 expression seems to be a very useful factor that should be in combination with HER2 and ER in breast cancer prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Callagy GM, Webber MJ, Pharoah PDP, Caldas C. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer. BMC Cancer. 2008;8:153.

    Article  PubMed  Google Scholar 

  2. McDonnell TJ, Korsmeyer SJ. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t (14; 18). Nature. 1991;349:254–6.

    Article  PubMed  CAS  Google Scholar 

  3. McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, Tu SM, Campbell ML. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res. 1992;52:6940–4.

    PubMed  CAS  Google Scholar 

  4. Pietenpol JA, Papadopoulos N, Markowitz S, Willson JK, Kinzler KW, Vogelstein B. Paradoxical inhibition of solid tumor cell growth by bcl2. Cancer Res. 1994;54:3714–7.

    PubMed  CAS  Google Scholar 

  5. Van Slooten HJ, Clahsen PC, van Dierendonck JH, Duval C, Pallud C, Mandard AM, Delobelle-Deroide A, van de Velde CJ, van de Vijver MJ. Expression of Bcl-2 in node-negative breast cancer is associated with various prognostic factors, but does not predict response to onecourse of perioperative chemotherapy. Br J Cancer. 1996;74:78–85.

    Article  PubMed  Google Scholar 

  6. Linjawi A, Kontogiannea M, Halwani F, Edwardes M, Meterissian S. Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer. J Am Coll Surg. 2004;198:83–90.

    Article  PubMed  Google Scholar 

  7. Lee KH, Im SA, Oh DY, Lee SH, Chie EK, Han W, Kim DW, Kim TY, Park IA, Noh DY, Heo DS, Ha SW, Bang YJ. Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy. BMC Cancer. 2007;7:63.

    Article  PubMed  Google Scholar 

  8. Nadler Y, Camp RL, Giltnane JM, Moeder C, Rimm DL, Kluger HM, Kluger Y. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Res. 2008;10:R35.

    Article  PubMed  Google Scholar 

  9. Bhargava V, Kell DL, Van de Rijn M, Warnke RA. Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity. Am J Pathol. 1994;145:535–40.

    PubMed  CAS  Google Scholar 

  10. Bilalovic N, Vranic S, Hasanagic S, Basic H, Tatarevic A, Beslija S. The Bcl-2 protein: a prognostic indicator strongly related to ER and PR in breast cancer. Bosn J Basic Med Sci. 2004;4:5–12.

    PubMed  Google Scholar 

  11. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–37.

    Article  PubMed  CAS  Google Scholar 

  12. McKean-Cowdin R, Kolonel LN, Press MF, Pike MC, Henderson BE. Germ-line HER-2 variant and breast cancer risk by stage of disease. Cancer Res. 2001;61:8393–4.

    PubMed  CAS  Google Scholar 

  13. Tommasi S, Fedele V, Crapolicchio A, Bellizzi A, Paradiso A, Reshkin SJ. ErbB2 and the antimetastatic nm23/NDP kinase in regulating serum induced breast cancer invasion. Int J Mol Med. 2003;12:131–4.

    PubMed  CAS  Google Scholar 

  14. Picard D, Bunone G, Liu JW, Donzw O. Steroid independent activation of steroid receptors in mammalian and yeast cells and in breast cancer. Biochem Soc Trans. 1997;25:597–602.

    PubMed  CAS  Google Scholar 

  15. McGuire WL. Hormone receptors: their role in predicting prognosis and response to endocrine therapy. Semin Oncol. 1978;5:428–33.

    PubMed  CAS  Google Scholar 

  16. Clarke R, Skaar T, Baumann K, Leonessa F, James M, Lippman J, Thompson EW, Freter C, Brunner N. Hormonol carcinogenesis in breast cancer: cellular and molecular studies of malignant progression. Breast Cancer Res Treat. 1994;31:237–48.

    Article  PubMed  CAS  Google Scholar 

  17. Nicholson RI, McClelland RA, Gee JM, Manning DL, Cannon P, Robertson JF, Ellis IO, Blamey RW. Epidermal growth factor receptor expression in breast cancer: association with response to endocrine therapy. Breast Cancer Res Treat. 1994;29:117–25.

    Article  PubMed  CAS  Google Scholar 

  18. Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ. Gene expression profiling and histopathological characterization of triple negative/basal-like breast carcinomas. Breast Cancer Res. 2007;R9:65.

    Article  Google Scholar 

  19. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumors. Nature. 2000;406:747–52.

    Article  PubMed  CAS  Google Scholar 

  20. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8:235–44.

    Article  PubMed  Google Scholar 

  21. Grann VR, Troxel AB, Zojwalla NJ, Jacobson JS, Hershman D, Neugut AI. Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma. Cancer. 2005;103:2241–51.

    Article  PubMed  CAS  Google Scholar 

  22. Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer: a study of 1,409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957;11:359–77.

    Article  PubMed  CAS  Google Scholar 

  23. Khabir A, Ghorbel A, Daoud J, Frikha M, Drira MM, Laplanche A, Busson P, Jlidi R. Similar BCL-X but different BCL-2 levels in the two age groups of North African nasopharyngeal carcinomas. Cancer Detect Prev. 2003;27:250–5.

    Article  PubMed  Google Scholar 

  24. BenHassen H, Masmoudi F, Rebai A. Inference in signal transduction pathways with incomplete data: comparison between the EM algorithm and a new implicit algorithm. J Comput Biol. 2009;16:1227–40.

    Article  CAS  Google Scholar 

  25. Bouchaala L, Masmoudi A, Rebai A. Improving algorithms for structure learning in Bayesian networks using a new implicit score. Expert Syst Appl. 2010;37:5470–5.

    Article  Google Scholar 

  26. Sivridis E, Stamos C, Fiska A, Nikolettos N, Koukourakis MI, Giatromanolaki A.c-erbB-2 and the “triple-state” in early breast carcinomas. Med Oncol 2009.

  27. Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ. BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci. 1991;88:6961–5.

    Article  PubMed  CAS  Google Scholar 

  28. Chao DT, Korsmeyer SJ. BCL-2 family: regulators of cell death. Annu Rev Immunol. 1998;16:395–419.

    Article  PubMed  CAS  Google Scholar 

  29. Luna-Moré S, Casquero S, Pérez-Mellado A, Rius F, Weill B, Gornemann I. Importance of estrogen receptors for the behavior of invasive micropapillary carcinoma of the breast. Review of 68 cases with follow-up of 54. Pathol Res Pract. 2000;196:35–9.

    Article  PubMed  Google Scholar 

  30. Wang S, Yang D, Lippman ME. Targeting Bcl-2 and Bcl-XL with non peptidic small-molecule antagonists. Semin Oncol. 2003;30:132–42.

    Article  Google Scholar 

  31. Rehman S, Crow J, Revell PA. Bax protein expression in DCIS of the breast in relation to invasive ductal carcinoma and other molecular markers. Pathol Oncol Res. 2000;6:256–63.

    Article  PubMed  CAS  Google Scholar 

  32. Sierra A, Castellsague X, Escobedo A, Lloveras B, Garcia-Ramirez M, Moreno A, Fabra A. Bcl2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer. Int J Cancer. 2000;89:142–7.

    Article  PubMed  CAS  Google Scholar 

  33. Fernandez Y, Gu B, Martinez A, Torregrosa A, Sierra A. Inhibition of apoptosis in human breast cancer cells: role in tumor progression to the metastatic state. Int J Cancer. 2002;101:317–26.

    Article  PubMed  CAS  Google Scholar 

  34. Gasparini G, Barbareschi M, Doglioni C, Palma PD, Mauri FA, Boracchi P, Bevilacqua P, Caffo O, Morelli L, Verderio P, Pezzella F, Harris AL. Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer. Clin Cancer Res. 1995;1:189–98.

    PubMed  CAS  Google Scholar 

  35. Tsutsui S, Yasuda K, Suzuki K, Takeuchi H, Nishizaki T, Higashi H, Sf Era. Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer. BMC Cancer. 2006;6:187.

    Article  PubMed  Google Scholar 

  36. Elledge RM, Green S, Howes L, Clark GM, Berardo M, Allred DC, Pugh R, Ciocca D, Radvin P, O’sullivan J, Rivkin S, Martino S, Osborne CK. bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a southwest oncology group study. J Clin Oncol. 1997;15:1916–22.

    PubMed  CAS  Google Scholar 

  37. Yang Q, Sakurai T, Jing X, Utsunomiya H, Shan L, Nakamura Y, Nakamura M, Oura S, Suzuma T, Yoshimura G, Umemura T, Kokawa Y, Nakudo K. Expression of Bcl2, but not Bax, correlates with estrogen receptor status and tumour proliferation in invasive breast carcinoma. Pathol Int. 1999;49:775–80.

    Article  PubMed  CAS  Google Scholar 

  38. Kyndi M, Sorensen FB, Knudsen H, Alsner J, Overgaard M, Nielsen HM, Overgaard J. Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b&c. Acta Oncol. 2008;47:608–17.

    Article  PubMed  CAS  Google Scholar 

  39. Kroger N, Langosch KM, Riethdorf S, Schmoor C, Schumacher M, Zander AR, Loning T. Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients. Clin Cancer Res. 2006;12(1):159–68.

    Article  PubMed  Google Scholar 

  40. Masmoudi Y, Chabchoub H, Hanafi S, Rebai A. A Mathematical Programming based Procedure for Breast Cancer Classification. J Math Model Algorithms. 2010; in press.

  41. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA. Triple negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.

    Article  PubMed  Google Scholar 

  42. Rakha EA, EL-Sayed ME, Grenn AR, Lee AH, Robertson JF. Ellis IO: prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32.

    Article  PubMed  CAS  Google Scholar 

  43. Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM. Phenotypic evaluation of the basal-like subtype of invasive breast carcinomas. Mod Pathol. 2006;19:264–71.

    Article  PubMed  CAS  Google Scholar 

  44. Fulford LG, Easton DF, Reis-Filho JS, Sofronis A, Gillett CE, Lakhani SR, Hanby A. Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast. Histopathology. 2006;49:22–34.

    Article  PubMed  CAS  Google Scholar 

  45. William J, Irvin Jr, Lisa A. Carey: what is triple-negative breast cancer. Eur J Cancer. 2008;44:2799–805.

    Article  Google Scholar 

  46. Rolland P, Spendlove I, Madjd Z, Rakha EA, Patel P, Ellis IO, Durrant L. The p53 positive Bcl-2 negative phenotype is an independent marker of prognosis in breast cancer. Int J Cancer. 2007;120:1311–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Mrs Raoudha Abdelnadher for the technical assistance and all of the clinicians and pathologists at Habib BOURGUIBA Hospital, who performed diagnosis, treatment and follow-up. We thank Dr Sami Baccouche for his valuable discussion and advices during this study. We also thank Mrs Salma Hamsa, for English editing of the manuscript.

Author information

Authors and Affiliations

  1. Bioinformatics and Signalling Unit, Centre of Biotechnology of Sfax, P.O. Box ‘1177’, 3018, Sfax, Tunisia

    Imen Kallel-Bayoudh, Hanen Ben Hassen, Sami Aifa & Ahmed Rebaï

  2. Department of Pathology, Habib BOURGUIBA Hospital, Sfax, Tunisia

    Abdelmajid Khabir & Tahia Sallemi-Boudawara

  3. Department of Radiotherapy, Habib BOURGUIBA Hospital, Sfax, Tunisia

    Noureddine Boujelbene & Jamel Daoud

  4. Department of Gynaecology, Hedi CHAKER Hospital, Sfax, Tunisia

    Mounir Frikha

Authors
  1. Imen Kallel-Bayoudh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanen Ben Hassen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdelmajid Khabir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Noureddine Boujelbene
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jamel Daoud
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mounir Frikha
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tahia Sallemi-Boudawara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sami Aifa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ahmed Rebaï
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed Rebaï.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 18 kb)

Supplementary material 2 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kallel-Bayoudh, I., Hassen, H.B., Khabir, A. et al. Bcl-2 expression and triple negative profile in breast carcinoma. Med Oncol 28 (Suppl 1), 55–61 (2011). https://doi.org/10.1007/s12032-010-9694-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9694-x

Keywords

Search

Navigation