Expression of Ki-67 and Bcl-2 biomarkers in normal breast tissue from women of reproductive age treated with raloxifene

Lima, Marina Ayres Vilarinho Corrêa; Silva, Benedito Borges da

doi:10.1007/s00404-011-1932-8

Cited by 4 publications

(8 citation statements)

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“…However, it appears that Bcl2 expression is not related to lymph node status and tumor stages [ 58 59 ]. Moreover, Bcl2 expression in normal and pathological conditions seems to depend on reproductive and hormonal factors [ 59 60 61 62 ]. Bargou et al [ 59 ] demonstrated that there are no differences between Bcl2 expression in the normal breast epithelium, nonmalignant cell lines, and breast cancer.…”

Section: Controversial Markers Of Normal Breast Tissue With Potentialmentioning

confidence: 99%

“…It was demonstrated that Bcl2 is positively correlated with ER and PR expression [ 59 ]. In a study performed on fibroadenomas of the breast, Lima and da Silva [ 61 ] have concluded that there were no differences in Bcl2 expression after placebo or raloxifene treatment. Differential expression of Bcl2 found in normal human breast tissue is cell-phenotype related and supports the fact that not all mammary cell types are equally responsive to apoptotic stimuli [ 63 ].…”

Section: Controversial Markers Of Normal Breast Tissue With Potentialmentioning

confidence: 99%

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Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis

et al. 2016

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Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis.

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Section: Controversial Markers Of Normal Breast Tissue With Potentialmentioning

confidence: 99%

Section: Controversial Markers Of Normal Breast Tissue With Potentialmentioning

confidence: 99%

Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis

et al. 2016

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“…The absence of a placebo control group may be considered a limitation of the present study; however, since the model used has been previously tested with success, 14 , 15 a placebo group was not believed to be necessary in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…12 The capacity of both tamoxifen and raloxifene to reduce the proliferative activity of the normal breast epithelium in premenopausal women has also been well established in previous studies. 13–15 Nevertheless, a direct comparison of the proliferative activity of these two compounds in the normal breast epithelium and their potential use as chemoprevention in premenopausal women are issues that remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

Effect of Tamoxifen and Raloxifene on the Proliferative Activity of the Breast Epithelium in Premenopausal Women

Lucato

Freitas‐Junior

Moreira

et al. 2015

Clin Med Insights Oncol

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OBJECTIVESTo compare the effects of tamoxifen and raloxifene on the proliferative activity of normal breast tissue in premenopausal women as measured by Ki-67/MIB-1 expression.STUDY DESIGNA total of 48 women with benign breast nodules and a recommendation for surgical removal of the lesion took part in this study. They were randomized to use tamoxifen or raloxifene for 22 days, after which they were submitted to surgery. During the surgical procedure, a 1-cm fragment of normal breast tissue was removed to study Ki-67 expression.RESULTSThe mean percentage ratios between immunolabeled and non-labeled cells were 2.02 ± 1.09 and 3.13 ± 3.23 for the tamoxifen and raloxifene groups, respectively. There was no statistically significant difference between the tamoxifen (n = 16) and raloxifene (n = 14) groups in relation to the immunohistochemical analysis of Ki-67 (P = 0.205).CONCLUSIONThe results of this study showed no difference between tamoxifen and raloxifene with respect to the potential of these drugs to reduce the proliferative activity of the normal breast epithelium in premenopausal women.

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“…We used multicolor stainings to study the stem cell markers p63 [32][33][34][35][36][37][38], K5, and K14 [1,39], the differentiation markers and luminal keratins K18, K8/18, and K19 [1,[40][41][42][43][44][45][46], and the myoepithelial lineage markers smooth muscle actin (SMA) [47,48], smooth muscle myosin heavy chain [49], calponin [50,51], and CD10 [47,[52][53][54][55]. We also evaluated the functional markers estrogen receptor (ER)-alpha [5,23,29,[56][57][58][59][60][61] and Ki67 [62][63][64][65][66]. Based on our findings, we propose a modified concept of the cellular hierarchy of human breast epithelium, including K5+ luminal lineage progenitor cells in the ductal-lobular axis and p63+K5+ progenitor cells confined to nipple ducts.…”

Section: Introductionmentioning

confidence: 99%

Spatially correlated phenotyping reveals K5-positive luminal progenitor cells and p63-K5/14-positive stem cell-like cells in human breast epithelium

Boecker¹,

Horn

Stenman

et al. 2018

Laboratory Investigation

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Understanding the mechanisms regulating human mammary epithelium requires knowledge of the cellular constituents of this tissue. Different and partially contradictory definitions and concepts describing the cellular hierarchy of mammary epithelium have been proposed, including our studies of keratins K5 and/or K14 as markers of progenitor cells. Furthermore, we and others have suggested that the p53 homolog p63 is a marker of human breast epithelial stem cells. In this investigation, we expand our previous studies by testing whether immunohistochemical staining with monospecific anti-keratin antibodies in combination with an antibody against the stem cell marker p63 might help refine the different morphologic phenotypes in normal breast epithelium. We used in situ multilabel staining for p63, different keratins, the myoepithelial marker smooth muscle actin (SMA), the estrogen receptor (ER), and Ki67 to dissect and quantify the cellular components of 16 normal pre- and postmenopausal human breast epithelial tissue samples at the single-cell level. Importantly, we confirm the existence of K5+ only cells and suggest that they, in contrast to the current view, are key luminal precursor cells from which K8/18+ progeny cells evolve. These cells are further modified by the expression of ER and Ki67. We have also identified a population of p63+K5+ cells that are only found in nipple ducts. Based on our findings, we propose a new concept of the cellular hierarchy of human breast epithelium, including K5 luminal lineage progenitors throughout the ductal-lobular axis and p63+K5+ progenitors confined to the nipple ducts.

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Expression of Ki-67 and Bcl-2 biomarkers in normal breast tissue from women of reproductive age treated with raloxifene

Abstract: Raloxifene treatment significantly reduced antigen expression of Ki-67, but failed to have any significant results on the Bcl-2 expression. Further studies are warranted to evaluate the mechanism of raloxifene on apoptosis in normal breast tissue.

Cited by 4 publications

References 24 publications

Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis

Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis

Effect of Tamoxifen and Raloxifene on the Proliferative Activity of the Breast Epithelium in Premenopausal Women

Spatially correlated phenotyping reveals K5-positive luminal progenitor cells and p63-K5/14-positive stem cell-like cells in human breast epithelium

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