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Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers

  • Published : 2013.02.28

Abstract

Background: Prognostication of breast cancer using clinico-pathologic variables, although useful, remains imperfect. Recent research has focused on finding new markers of prognosis using gene expression profiling. Panels of proteins assessed by immunohistochemistry might also be useful in this regard. This study focused on Bcl-2 protein expression in triple-negative (TNBC) and non- triple-negative breast cancer (non-TNBC) with correlation to clinico-pathologic variables. Materials and methods: We analyzed Bcl-2 expression in 77 women with primary breast carcinoma divided into two groups; triple-negative and non- triple-negative according to expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptors (Her2/neu). Bcl-2 expression was assessed in relation to age, histo-pathological subtype, grade, nodal status and tumor size. Results: Bcl-2 was expressed in 74% of triple-negative breast cancers and 70% of non- triple-negative cancers. In TNBC, expression was significantly correlated with invasive ductal subtype, while in non-TNBC it was significantly correlated with age and negative nodal status. In both groups higher Bcl-2 expression associated with favourable prognostic factors in breast cancer, but no significant statistical correlations were found. Conclusions: Frequency of Bcl-2 expression does not differ between TNBC and non-TNBC, but different prognostic factors correlate with Bcl-2 in the two cases.

References

  1. Abd El-Rehim DM, Ball G, Pinder SE, et al (2005). High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer, 116, 340-50. https://doi.org/10.1002/ijc.21004
  2. Bhargava V, Kell DL, Rijn M, et al (1994). Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity. Am J Pathol, 145, 535-40.
  3. Bilalovic N, Vranic S, Hasanagic S, et al (2004). The Bcl-2 protein: a prognostic indicator strongly elated to ER and PR in breast cancer. Bosn J Basic Med Sci, 4, 5-12.
  4. Callagy G, Cattaneo E, Daigo Y, et al (2003). Molecular classification of breast carcinomas using tissue microarrays. Diagn Mol Pathol, 12, 27-34. https://doi.org/10.1097/00019606-200303000-00004
  5. Callagy GM, Pharoah PD, Pinder SE, et al (2006). Bcl-2 is a prognostic marker in breast cancer independently of the nottingham prognostic index. Clin Cancer Res, 12, 2468-75. https://doi.org/10.1158/1078-0432.CCR-05-2719
  6. Cecka F, Hornychova H, Melichar B, et al (2008). Expression of bcl-2 in breast cancer: correlation with clinicopathological characteristics and survival. Acta Medica(Hradec Kralove), 51, 107-12.
  7. Dawson SJ, Makretsov N, Blows FM, et al (2010). BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer, 103, 668-75. https://doi.org/10.1038/sj.bjc.6605736
  8. De Giorgi U, Rosti G, Frassineti L, et al (2007). High-dose chemotherapy for triple negative breast cancer. Ann Oncol, 18, 202-3.
  9. de Ruijter TC, Veeck J, de Hoon JPJ, et al (2011). Characteristics of triple-negative breast cancer. J Cancer Res Clin Oncol,137, 183-92. https://doi.org/10.1007/s00432-010-0957-x
  10. dos Santos LG, Lopes-Costa PV, dos Santos AR, et al (2008). Bcl-2 oncogene expression in estrogen receptor-positive and negative breast carcinoma. Eur J Gynaecol Oncol, 29, 459-61.
  11. Ismail-Khan R, Bui MM (2010). A review of triple-negative breast cancer. Cancer Control, 17, 173-6.
  12. Jemal A, Siegel R, Ward E, et al (2007). Cancer statistics. CA Cancer J Clin, 57, 43-66. https://doi.org/10.3322/canjclin.57.1.43
  13. Kallel-Bayoudh I, Hassen HB, Khabir A, et al (2011). Bcl-2 expression and triple negative profile in breast carcinoma. Med Oncol, 28, 55-61. https://doi.org/10.1007/s12032-010-9694-x
  14. Kaplan HG, Malmgren JA, Atwood MK (2006). Impact of triple negative phenotype on breast cancer prognosis. Poster presented at: 29th Annual San Antonio Breast Cancer Symposium; December 14-17, San Antonio, TX.
  15. Kreike B, van Kouwenhove M, Horlings H, et al (2007). Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res, 9, 65. (doi:10.1186/bcr1771) https://doi.org/10.1186/bcr1771
  16. Kumar R, Vadlamudi RK, Adam L. (2000). Apoptosis in mammary gland and cancer. Endocr Relat Cancer, 7, 257-69. https://doi.org/10.1677/erc.0.0070257
  17. Lipponen P, Pietilainen T, Kosma VM et al (1995). Apoptosis suppressing protein bcl-2 is expressed in well-differentiated breast carcinomas with favourable prognosis. J Pathol, 177, 49-55. https://doi.org/10.1002/path.1711770109
  18. Mathieu MC, Rouzier R, Llombart-Cussac A et al (2004). The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur J Cancer,40, 342-51.
  19. Mimori K, Kataoka A, Yoshinaga K et al (2005). Identification of molecular markers for metastasis-related genes in primary breast cancer cells. Clin Exp Metastasis, 22, 59-67. https://doi.org/10.1007/s10585-005-4417-y
  20. Mottolese M, Benevolo M, Del Monte G et al(2000). Role of P53 and BCL-2 in high-risk breast cancer patients treated with adjuvant anthracycline-based chemotherapy. J Cancer Res Clin Oncol, 126, 722-9. https://doi.org/10.1007/PL00008478
  21. Munster PM, Norton L.(2001). Predictive factor for the response to adjuvant therapy with emphasis in breast cancer. Breast Cancer Res, 3, 361-4. https://doi.org/10.1186/bcr323
  22. Nadler Y, Camp RL, Giltnane JM et al (2008). Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Res, 10, 35 (doi:10.1186/bcr1998) https://doi.org/10.1186/bcr1998
  23. Neri A, Marrelli D, Roviello F et al (2006). Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer. Breast Cancer Res Treat, 99, 77-83. https://doi.org/10.1007/s10549-006-9183-2
  24. Paik S, Tang G, Shak S et al (2006). Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol, 24, 3726-34. https://doi.org/10.1200/JCO.2005.04.7985
  25. Park SH, Kim H, Song BJ. (2002). Down regulation of bcl2 expression in invasive ductal carcinomas is both estrogen and progesterone-receptor dependent and associated with poor prognostic factors. Pathol Oncol Res, 8, 26-30. https://doi.org/10.1007/BF03033697
  26. Perou CM, Sorlie T, Eisen MB et al (2000). Molecular portraits of human breast tumors. Nature, 406, 747-52. https://doi.org/10.1038/35021093
  27. Pinkas J, Martin SS, Leder P. (2004). Bcl-2-mediated cell survival promotes metastasis of EpH4 beta MEKDD mammary epithelial cells. Mol Cancer Res, 2, 551-6.
  28. Reed JC. (1994). Bcl-2 and the regulation of programmed cell death. J Cell Biol, 124, 1-6. https://doi.org/10.1083/jcb.124.1.1
  29. Reed JC, Miyashita T, Takayama S et al (1996). BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem, 60, 23-32. https://doi.org/10.1002/(SICI)1097-4644(19960101)60:1<23::AID-JCB5>3.0.CO;2-5
  30. Sorlie T, Perou CM, Tibshirani R et al (2001). Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA, 98, 10869-74. https://doi.org/10.1073/pnas.191367098
  31. Sorlie T, Tibshirani R, Parker J et al (2003). Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA, 100, 8418-23. https://doi.org/10.1073/pnas.0932692100
  32. Subhawong AP, Nassar H, Halushka MK et al (2010). Heterogeneity of Bcl-2 expression in metastatic breast carcinoma. Mod Pathol, 23,1089-96. https://doi.org/10.1038/modpathol.2010.93
  33. Tavassoli FA, Devilee P (2003). World health organization of tumors. Pathology and genetics of tumors of the breast and female genital organs. Lyon, IARC press.
  34. Tawfik O, Davis K, Kimler BF, et al (2010). Clinicopathological characteristics of triple-negative invasive mammary carcinomas in African-American versus Caucasian women. Ann Clin Lab Sci, 40, 315-23.
  35. Thomadaki H, Talieri M, Scorilas A (2007). Prognostic value of the apoptosis related genes BCL2 and BCL2L12 in breast cancer. Cancer Lett, 247, 48-55. https://doi.org/10.1016/j.canlet.2006.03.016
  36. Trere D, Montanaro L, Ceccarelli C, et al (2007). Prognostic relevance of a novel semiquantitative classification of Bcl2 immunohistochemical expression in human infiltrating ductal carcinomas of the breast. Ann Oncol, 18, 1004-14. https://doi.org/10.1093/annonc/mdm074
  37. Tsujimoto Y, Croce CM (1986). Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci USA, 83, 5214-8. https://doi.org/10.1073/pnas.83.14.5214
  38. Van't Veer LJ, Dai H, van de Vijver MJ, et al (2002). Gene expression profiling predicts clinical outcome of breast cancer. Nature, 415, 530-6. https://doi.org/10.1038/415530a
  39. Zinkel S, Gross A, Yang E (2006). BCL2 family in DNA damage and cell cycle control. Cell Death Differ, 13, 1351-9. https://doi.org/10.1038/sj.cdd.4401987

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