Label-free isolation and cultivation of patient-matched human mammary epithelial and stromal cells from normal breast tissue

Background:Loss of the stromally-restricted homeodomain transcription factor, Alx4, causes defective mouse mammary epithelial morphogenesis.Aims:To begin to define the role of ALX4 in the human breast and in breast cancer, the expression pattern of ALX4 in the normal human breast and changes in expression in breast cancer were determined.Methods:Cells expressing ALX4 in the human breast were identified by co-immunofluorescence using α-ALX4 antibodies and markers of specific mammary cell types. ALX4 expression in breast cancer was then determined by immunohistochemistry on tumour sections that also harboured regions of normal breast tissue. Using criteria that required ALX4 staining in both stromal and epithelial cells, changes in ALX4 expression in tumours on a tissue microarray were determined.Results:ALX4 was expressed in both stromal and luminal epithelial cells in the human breast. Scoring tissue sections of duct carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC) that also harboured regions of normal breast tissue, a loss of ALX4 (p<0.001) in stromal and epithelial cells in breast tumours was observed. Analysis of ALX4 expression in 123 sections on a tissue microarray confirmed a highly significant loss (p<0.001) of ALX4 in breast cancer in the tumours themselves and in adjacent stromal cells.Conclusions:These data show a distinct pattern of expression of ALX4 in the human breast relative to the murine mammary gland. Furthermore, characterisation of ALX4 in breast cancer showed that loss of ALX4 in tumours and the surrounding untransformed stroma is a basic characteristic of DCIS and IDC.

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Ezrin expression in primary breast cancer, metastatic lymph nodes and normal breast tissue

Geburtshilfe und Frauenheilkunde ◽

10.1055/s-0030-1254964 ◽

2010 ◽

Vol 70 (05) ◽

Author(s):

D Gschwantler-Kaulich ◽

C Natter ◽

S Steurer ◽

I Walter ◽

C Singer

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph ◽

Ezrin Expression

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Hormone Receptor Expression Variations in Normal Breast Tissue: Preliminary Results of a Prospective Observational Study

Journal of Personalized Medicine ◽

10.3390/jpm11050387 ◽

2021 ◽

Vol 11 (5) ◽

pp. 387

Author(s):

Giacomo Santandrea ◽

Chiara Bellarosa ◽

Dino Gibertoni ◽

Maria C. Cucchi ◽

Alejandro M. Sanchez ◽

...

Keyword(s):

Hormone Receptor ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Receptor Expression ◽

Hormonal Stimulation ◽

Tissue Samples ◽

Hormonal Receptor ◽

Hormone Receptor Expression ◽

Cystic Disease Fluid Protein

Normal breast tissue undergoes great variations during a woman’s life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.

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Expression of c-kit protein in cancer versus normal breast tissue

Współczesna Onkologia ◽

10.5114/wo.2012.30058 ◽

2012 ◽

Vol 4 ◽

pp. 306-309 ◽

Cited By ~ 1

Author(s):

Abdolhassan Talaiezadeh ◽

Seyed Nematollah Jazayeri ◽

Jamal Nateghi

Keyword(s):

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast

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Accelerated aging in normal breast tissue of women with breast cancer

Breast Cancer Research ◽

10.1186/s13058-021-01434-7 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Shoghag Panjarian ◽

Jozef Madzo ◽

Kelsey Keith ◽

Carolyn M. Slater ◽

Carmen Sapienza ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Anomaly Detection ◽

Breast Tissue ◽

Preventive Intervention ◽

Normal Breast Tissue ◽

Accelerated Aging ◽

Normal Breast ◽

Age Related ◽

Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

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Postmenopausal Dense Breasts Maintain Premenopausal Levels of GH and Insulin-like Growth Factor Binding Proteins in Vivo

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz323 ◽

2020 ◽

Vol 105 (5) ◽

pp. 1617-1628 ◽

Cited By ~ 1

Author(s):

Nina Dabrosin ◽

Charlotta Dabrosin

Keyword(s):

Postmenopausal Women ◽

Breast Density ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Dense Breast ◽

Breast Cancers ◽

Dense Breast Tissue ◽

Dense Breasts

Abstract Context Dense breast tissue is associated with 4 to 6 times higher risk of breast cancer by poorly understood mechanisms. No preventive therapy for this high-risk group is available. After menopause, breast density decreases due to involution of the mammary gland. In dense breast tissue, this process is haltered by undetermined biological actions. Growth hormone (GH) and insulin-like binding proteins (IGFBPs) play major roles in normal mammary gland development, but their roles in maintaining breast density are unknown. Objective To reveal in vivo levels of GH, IGFBPs, and other pro-tumorigenic proteins in the extracellular microenvironment in breast cancer, in normal breast tissue with various breast density in postmenopausal women, and premenopausal breasts. We also sought to determine possible correlations between these determinants. Setting and Design Microdialysis was used to collect extracellular in vivo proteins intratumorally from breast cancers before surgery and from normal human breast tissue from premenopausal women and postmenopausal women with mammographic dense or nondense breasts. Results Estrogen receptor positive breast cancers exhibited increased extracellular GH (P < .01). Dense breasts of postmenopausal women exhibited similar levels of GH as premenopausal breasts and significantly higher levels than in nondense breasts (P < .001). Similar results were found for IGFBP-1, -2, -3, and -7 (P < .01) and for IGFBP-6 (P <.05). Strong positive correlations were revealed between GH and IGFBPs and pro-tumorigenic matrix metalloproteinases, urokinase-type plasminogen activator, Interleukin 6, Interleukin 8, and vascular endothelial growth factor in normal breast tissue. Conclusions GH pathways may be targetable for cancer prevention therapeutics in postmenopausal women with dense breast tissue.

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