scholarly journals The Expression Pattern of Epidermal Differentiation Marker Keratin 10 in the Normal Human Breast and Breast Cancer Cells

2020 ◽  
Vol 68 (8) ◽  
pp. 561-570
Author(s):  
Jiyoung Kim ◽  
René Villadsen

Cells of the human breast gland express an array of keratins, of which some are used for characterizing both normal and neoplastic breast tissue. However, the expression pattern of certain keratins has yet to be detailed. Here, the expression of a differentiation marker of epidermal epithelium, keratin 10 (K10), was investigated in the human breast gland. While in normal breast tissue generally less than 1% of luminal epithelial cells expressed K10, in women >30 years of age glandular structures with K10-positive (K10pos) cells were found at higher frequency than in younger women. K10pos cells belong to a mature luminal compartment as they were negative for cKIT, positive for Ks20.8, and mostly non-cycling. In breast cancer, around 16% of primary breast carcinomas tested were positive for K10 by immunohistochemistry. Interestingly, K10pos tumor cells generally exhibit features of differentiation similar to their normal counterparts. Although this suggests that K10 is a marker of tumor differentiation, data based on gene expression analysis imply that high levels of K10 dictate a worse outcome for breast cancer patients. These findings can form the basis of future studies that should unravel which role K10 may play as a marker of breast cancer:

2009 ◽  
Vol 62 (10) ◽  
pp. 908-914 ◽  
Author(s):  
H Chang ◽  
N Mohabir ◽  
S Done ◽  
P A Hamel

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.


2006 ◽  
Vol 13 (2) ◽  
pp. 617-628 ◽  
Author(s):  
C L Wilson ◽  
A H Sims ◽  
A Howell ◽  
C J Miller ◽  
R B Clarke

Oestrogen (E) is essential for normal and cancer development in the breast, while anti-oestrogens have been shown to reduce the risk of the disease. However, little is known about the effect of E on gene expression in the normal human breast, particularly when the epithelium and stroma are intact. Previous expression profiles of the response to E have been performed on tumour cell lines, in the absence of stroma. We investigated gene expression in normal human breast tissue transplanted into 9–10-week-old female athymic nude (Balb/c nu/nu) mice. After 2 weeks, when epithelial proliferation is minimal, one-third of the mice were treated with 17β-oestradiol (E2) to give human luteal-phase levels in the mouse, which we have previously shown to induce maximal epithelial cell proliferation. RNA was isolated from treated and untreated mice, labelled and hybridized to Affymetrix HG-U133A (human) GeneChips. Gene expression levels were generated using BioConductor implementations of the RMA and MAS5 algorithms. E2 treatment was found to represent the largest source of variation in gene expression and cross-species hybridization of mouse RNA from xenograft samples was demonstrated to be negligible. Known E2-responsive genes (such as TFF1 and AREG), and genes thought to be involved in breast cancer metastasis (including mammoglobin, KRT19 and AGR2), were upregulated in response to E treatment. Genes known to be co-expressed with E receptor α in breast cancer cell lines and tumours were both upregulated (XBP-1 and GREB1) and downregulated (RARRES1 and GATA3). In addition, genes that are normally expressed in the myoepithelium and extracellular matrix that maintain the tissue microenvironment were also differentially expressed. This suggests that the response to oestrogen in normal breast is highly dependent upon epithelial–stromal/myoepithelial interactions which maintain the tissue microenvironment during epithelial cell proliferation.


2020 ◽  
Author(s):  
Toshiaki Akahane ◽  
Naoki Kanomata ◽  
Oi Harada ◽  
Tetsumasa Yamashita ◽  
Junichi Kurebayashi ◽  
...  

Abstract Background: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.Methods: Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.Conclusions: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.


2020 ◽  
Author(s):  
Shahan Mamoor

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of fibronectin, encoded by FN1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. FN1 expression in primary tumors of the breast was significantly higher than in normal breast tissue, and distant metastasis-free survival in breast cancer patients was significantly worse in patients with high tumor expression of FN1 than in patients with low tumor expression of FN1. FN1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.


2020 ◽  
Author(s):  
Shahan Mamoor

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of CD34 when comparing primary tumors of the breast to the tissue of origin, the normal breast. CD34 expression in primary tumors of the breast was significantly lower than in normal breast tissue, and relapse-free and overall survival in breast cancer patients was significantly worse CD34 patients with low tumor expression of CD34 than in patients with high tumor expression of CD34. CD34 may be of relevance to initiation, maintenance or progression of cancers of the female breast.


1986 ◽  
Vol 1 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Massimo Gion ◽  
Riccardo Mione ◽  
Ruggero Dittadi ◽  
Luciano Griggio ◽  
Gabriele Munegato ◽  
...  

The study of tumor markers in breast cancer tissue may supply information on the tumor's biological features and its clinical behaviour. Forty-nine primary breast cancer patients are evaluable to date. CEA, ferritin, TPA and CA15/3 were measured with radioimmu-nometric methods in the cytosol of carcinoma and normal tissue from the same breast. The concentrations of the four markers were higher in the tumor than in normal tissue in 42/49 cases for CEA, 47/49 for ferritin, 42/49 for TPA and in 24/29 for CA15/3. However, an overlap was found between carcinoma and normal tissue levels, particularly for CEA and TPA. We can conclude that the four substances studied may be markers of malignancy in breast carcinoma when nonmalignant breast tissue from the same patient is determined at the same time, whereas assays within a single, unknown breast tissue sample may be useful only in the case of ferritin and, partly, CA15/3.


Sign in / Sign up

Export Citation Format

Share Document