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 immunonegative 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.
MeSH Terms
Adult
Breast Neoplasms/metabolism,pathology
Carcinoma, Ductal, Breast/metabolism,pathology
Carcinoma, Intraductal, Noninfiltrating/metabolism,pathology
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Prognosis
Proto-Oncogene Proteins c-bcl-2/biosynthesis,genetics
Receptor, ErbB-2/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Tumor Suppressor Protein p53/metabolism
Chemicals
Proto-Oncogene Proteins c-bcl-2
Receptors, Estrogen
Receptors, Progesterone
Tumor Suppressor Protein p53
Receptor, ErbB-2
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Park Sung-Hye
Inje University, College of Medicine, Ilsan Paik Hospital, Department of Anatomical Pathology 2240 Daewha-dong, Ilsan-gu, Koyang-city, 411-706, Korea. sunghye@ilsanpaik.ac.kr
Kim Hanseong
Song Byung-Joo
References (22)
22 references, click to expand
-
BCL-2 family: regulators of cell death.
Annu Rev Immunol. 1998;16:395-419
PMID: 9597135
-
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(1):35-9
PMID: 10674270
-
BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6961-5
PMID: 1871110
-
Bcl-2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors.
J Immunol. 1998 Aug 1;161(3):1433-8
PMID: 9686608
-
Differential effects of chemotherapeutic agents on the Bcl-2/Bax apoptosis pathway in human breast cancer cell line MCF-7.
Breast Cancer Res Treat. 1999 May;55(1):73-83
PMID: 10472781
-
Bcl2, p53 and clinical outcome in a series of 138 operable breast cancer patients.
Anticancer Res. 1999 Sep-Oct;19(5C):4555-63
PMID: 10650810
-
Bax protein expression in DCIS of the breast in relation to invasive ductal carcinoma and other molecular markers.
Pathol Oncol Res. 2000;6(4):256-63
PMID: 11173657
-
Chemosensitisation of malignant melanoma by BCL2 antisense therapy.
Lancet. 2000 Nov 18;356(9243):1728-33
PMID: 11095261
-
Apoptosis and chemotherapy resistance.
Eur J Cancer. 1996 Jun;32A(6):921-6
PMID: 8763333
-
Bcl-2 slows in vitro breast cancer growth despite its antiapoptotic effect.
J Surg Res. 1998 Apr;76(1):22-6
PMID: 9695733
-
Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers.
Hum Pathol. 2001 May;32(5):487-93
PMID: 11381366
-
Overexpression of Bcl-XS sensitizes MCF-7 cells to chemotherapy-induced apoptosis.
Cancer Res. 1995 Jun 15;55(12):2507-10
PMID: 7780958
-
Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 proto-oncogene expression in human breast cancer cells.
Cancer Res. 1995 Sep 1;55(17 ):3902-7
PMID: 7641210
-
Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity.
Am J Pathol. 1994 Sep;145(3):535-40
PMID: 8080038
-
The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients.
J Natl Cancer Inst. 1994 Apr 6;86(7):499-504
PMID: 8133533
-
The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model.
Am J Pathol. 1995 Jan;146(1):20-6
PMID: 7856728
-
Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer.
Clin Cancer Res. 1995 Feb;1(2):189-98
PMID: 9815973
-
Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases.
Cancer J Sci Am. 1997 Jul-Aug;3(4):230-7
PMID: 9263629
-
Apoptosis in mammary gland and cancer.
Endocr Relat Cancer. 2000 Dec;7(4):257-69
PMID: 11174847
-
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. 1997 Oct 24;1333(2):F151-78
PMID: 9395285
-
BCL-2 family members and the mitochondria in apoptosis.
Genes Dev. 1999 Aug 1;13(15):1899-911
PMID: 10444588
-
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. 1999 Dec;15(6):1137-47
PMID: 10568820