Down regulation of Bc12 expression in invasive ductal carcinomas is both estrogen- and progesterone-receptor dependent and associated with poor prognostic factors (original) (raw)

Abstract

In normal breast, Bcl2 is expressed in the non-pregnant and non-involuting mammary epithelium. The exact mechanism and the effect of the down regulation of the Bcl2 expression on breast cancer cells are not clearly defined. We compared down regulation as well as the persistent expression of Bcl2 with ER, PR, p53, and c-erb-B2 overexpression and clinicopathologic variables, and tumor stage in 11 cases of ductal carcinomas in situ (DCIS) and 44 cases of invasive ductal carcinomas (IDC) of Korean women by immunohistochemical studies. Bcl2 down regulation was found in 39% of IDC and in 18% of DCIS cases. In IDC, while persistent Bcl2 expression was displayed in 95% and 78.9% of ER and PR immunoreactive ones and 71.9 % of c-erb-B2 immnonegative ones. Seventeen cases of Bcl2 down regulated IDC had a significant correlation with ER negativity (94.1%), PR negativity, (76.5%), and high nuclear (61.1% is grade III) and histological grade (76% is grade III). However, in DCIS, no significant correlation between the Bcl2 expression and various parameters were obtained, probably due to small sample size. In conclusion, the Bcl2 expression was both ER and PR dependent and down regulation of Bcl2 in IDC was significantly correlated with poor prognostic factors.

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References

  1. Strasser A, Huang DC, Vaux DL: The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy. Biochim Biophys Acta 1333:F151–178, 1997.
    PubMed CAS Google Scholar
  2. Hockenbery DM, Zutter M, Hickey W, et al: BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci 88:6961–6965, 1991.
    Article PubMed CAS Google Scholar
  3. Chao DT, Korsmeyer SJ: BCL-2 family: regulators of cell death. Annu Rev Immunology 16:395–419, 1998.
    Article CAS Google Scholar
  4. Bonnotte B, Favre N, Moutet M, et al: Bcl-2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors. J Immunol 161:1433–1438, 1998.
    PubMed CAS Google Scholar
  5. Gross A, McDonnell JM, Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911, 1999.
    Article PubMed CAS Google Scholar
  6. Knowlton K, Mancini M, Creason S, et al Bcl-2 slows in vitro breast cancer growth despite its antiapoptotic effect. J Surg Res 76:22–26, 1998.
    Article PubMed CAS Google Scholar
  7. Kumar R, Vadlamudi RK, Adam L: Apoptosis in mammary gland and cancer. Endocr Relat Cancer 7:257–69, 2000.
    Article PubMed CAS Google Scholar
  8. Hickman JA: Apoptosis and chemotherapy resistance. Eur J Cancer 32A:921–926, 1996.
    Article PubMed CAS Google Scholar
  9. Jansen B, Wacheck V, Heere-Ress E, et al Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet 356:1728–1733, 2000.
    Article PubMed CAS Google Scholar
  10. 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 6:256–263, 2000.
    Article PubMed CAS Google Scholar
  11. Castiglione F, Sarotto I, Fontana V, et al: Bcl2, p53 and clinical outcome in a series of 138 operable breast cancer patients. Anticancer Res 19:4555–4563, 1999.
    PubMed CAS Google Scholar
  12. Mauri FA, Maisonneuve P, Caffo O, et al Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up. Int J Oncol 15:1137–1147, 1999.
    PubMed CAS Google Scholar
  13. Olopade OI, Adeyanju MO, Safa AR, et al: Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J Sci Am 3:230–237, 1997.
    PubMed CAS Google Scholar
  14. Gasparini G, Barbareschi M, Doglioni C, et al: Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer. Clin Cancer Res 1:189–198, 1995.
    PubMed CAS Google Scholar
  15. Silvestrini R, Veneroni S, Daidone MG, et al.: The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. J Natl Cancer Inst 86: 499–504, 1994.
    Article PubMed CAS Google Scholar
  16. Bhargava V, Kell DL, van de Rijn M, et al: Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity. Am J Pathol 145:535–540, 1994.
    PubMed CAS Google Scholar
  17. Bronner MP, Culin C, Reed JC, et al: The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. Am J Pathol 146:20–26, 1995.
    PubMed CAS Google Scholar
  18. Teixeira C, Reed JC, Pratt MA: Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 protooncogene expression in human breast cancer cells. Cancer Res 55:3902–3907, 1995.
    PubMed CAS Google Scholar
  19. Luna-More S, Casquero S, Perez-Mellado A, et al: Importance of estrogen receptors for the behavior of invasive micropapillary carcinoma of the breast. Review of 68 cases with followup of 54. Pathol Res Pract 196:35–39, 2000.
    PubMed CAS Google Scholar
  20. Leal C, Henrique R, Monteiro P, et al: Apocrine ductal carcinoma in situ of the breast: histologie classification and expression of biologic markers. Hum Pathol 32:487–493, 2001.
    Article PubMed CAS Google Scholar
  21. Sumantran VN, Ealovega MW, Nunez G, et al: Overexpression of Bcl-XS sensitizes MCF-7 cells to chemotherapy-induced apoptosis. Cancer Res 55:2507–2510, 1995.
    PubMed CAS Google Scholar
  22. Leung LK, Wang TT: Differential effects of chemotherapeutic agents on the Bcl-2/Bax apoptosis pathway in human breast cancer cell line MCF-7. Breast Cancer Res Treat 55:73–83, 1999.
    Article PubMed CAS Google Scholar

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Authors and Affiliations

  1. Department of Anatomical Pathology, Inje University, College of Medicine, Ilsan Paik Hospital, Kyunggi-do, Korea
    Sung-Hye Park & Hanseong Kim
  2. Department of General Surgery, Inje University, College of Medicine, Ilsan Paik Hospital, Kyunggi-do, Korea
    Byung-Joo Song

Authors

  1. Sung-Hye Park
  2. Hanseong Kim
  3. Byung-Joo Song

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Correspondence toSung-Hye Park.

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Park, SH., Kim, H. & Song, BJ. Down regulation of Bc12 expression in invasive ductal carcinomas is both estrogen- and progesterone-receptor dependent and associated with poor prognostic factors.Pathol. Oncol. Res. 8, 26–30 (2002). https://doi.org/10.1007/BF03033697

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