scholarly journals Matrix Metalloproteinase Expression Patterns in Luminal A Type Breast Carcinomas

2007 ◽  
Vol 23 (3) ◽  
pp. 189-196 ◽  
Author(s):  
J. Decock ◽  
W. Hendrickx ◽  
M. Drijkoningen ◽  
H. Wildiers ◽  
P. Neven ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Expression Patterns ◽  
Menopausal Status ◽  
Clinicopathological Parameters ◽  
Rna Expression ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Aberrant Expression ◽  
Ductal Carcinomas

Objective:Aberrant expression of individual matrix metalloproteinases has been associated with poor prognosis in various human carcinomas. The current study aimed at defining an RNA expression profile of various MMPs in breast cancer and correlating their expression with clinicopathological parameters.Methods:The RNA expression patterns of 6 MMPs (MMP2, MMP8, MMP9, MMP10, MMP11, MMP13) were determined in 25 breast carcinomas using quantitative RT-PCR and correlated with clinicopathological parameters, including menopausal status, tumor size and grade, and lymph node involvement.Results:We observed high MMP2 levels more frequently in premenopausal than in postmenopausal women (p= 0.02). Analysis of luminal A type invasive ductal carcinomas (19/25), revealed an even stronger association of MMP2 with menopausal status (p= 0.005). Within this subgroup, we also found a correlation between MMP11 and menopausal status (p= 0.02). No correlation was found between MMP expressions and other clinicopathological parameters. In co-expression analyses MMP2-MMP10 and MMP8-MMP9 showed a weak correlation of their expression.Conclusions:Although this is a pilot study, our findings indicate that luminal A invasive ductal carcinomas commonly express high MMP2 and MMP11 levels in premenopausal breast cancer patients and suggest a co-regulation of MMP2-MMP10 and MMP8-MMP9.

scholarly journals Role of miR-10b-5p in the prognosis of breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7728 ◽  
Author(s):  
Junmin Wang ◽  
Yanyun Yan ◽  
Zhiqi Zhang ◽  
Yali Li
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cancer Development ◽  
Clinicopathological Parameters ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Ppi Networks

Breast cancer is the leading cause of cancer-related death in women worldwide. Aberrant expression levels of miR-10b-5p in breast cancer has been reported while the molecular mechanism of miR-10b-5p in tumorigenesis remains elusive. Therefore, this study was aimed to investigate the role of miR-10b-5p in breast cancer and the network of its target genes using bioinformatics analysis. In this study, the expression profiles and prognostic value of miR-10b-5p in breast cancer were analyzed from public databases. Association between miR-10b-5p and clinicopathological parameters were analyzed by non-parametric test. Moreover, the optimal target genes of miR-10b-5p were obtained and their expression patterns were examined using starBase and HPA database. Additionally, the role of these target genes in cancer development were explored via Cancer Hallmarks Analytics Tool (CHAT). The protein–protein interaction (PPI) networks were constructed to further investigate the interactive relationships among these genes. Furthermore, GO, KEGG pathway and Reactome pathway analyses were carried out to decipher functions of these target genes. Results demonstrated that miR-10b-5p was down-regulated in breast cancer and low expression of miR-10b-5p was significantly correlated to worse outcome. Five genes, BIRC5, E2F2, KIF2C, FOXM1, and MCM5, were considered as potential key target genes of miR-10b-5p. As expected, higher expression levels of these genes were observed in breast cancer tissues than in normal tissues. Moreover, analysis from CHAT revealed that these genes were mainly involved in sustaining proliferative signaling in cancer development. In addition, PPI networks analysis revealed strong interactions between target genes. GO, KEGG, and Reactome pathway analysis suggested that these target genes of miR-10b-5p in breast cancer were significantly involved in cell cycle. Predicted target genes were further validated by qRT-PCR analysis in human breast cancer cell line MDA-MB-231 transfected with miR-10b mimic or antisense inhibitors. Taken together, our data suggest that miR-10b-5p functions to impede breast carcinoma progression via regulation of its key target genes and hopefully serves as a potential diagnostic and prognostic marker for breast cancer.

scholarly journals Expression of ICOSL is associated with decreased survival in invasive breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6903 ◽  
Author(s):  
Bin Wang ◽  
Huayong Jiang ◽  
Tingyang Zhou ◽  
Ning Ma ◽  
Wei Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Breast Tumor ◽  
Critical Role ◽  
Menopausal Status ◽  
Chinese Patients ◽  
Clinicopathological Parameters ◽  
Depth Of Invasion ◽  
Breast Carcinomas ◽  
Invasive Breast Carcinomas

Background Inducible co-stimulator (ICOS) is a CD28-related molecule exclusively expressed on activated T cells and plays a critical role in modulating the immune response in breast cancer. The blockage of ICOS pathway has been shown to inhibit the activity of Type 2 T helper cells, thus potentially protecting against cancer growth. The current study aims to investigate the correlation between inducible co-stimulator ligand (ICOSL) expression in tumor tissues and the prognoses of patients with invasive breast cancer. Methods Tumor samples from 562 Chinese patients with invasive breast carcinomas were collected between 2003 and 2010. The expression of ICOSL on breast tumor and adjacent non-cancerous tissue was determined via immunohistochemistry. The overall survival (OS) of patients with positive and negative ICOSL expression were described using Kaplan–Meier curves, respectively. Parametric correlation method was used to analyze the correlation between ICOSL expression and other clinicopathological parameters. ICOSL was selected as a dependent variable for multivariate analysis. Results Positive ICOSL expression was identified on the plasma membrane in both cytoplasm and the nucleus of breast cancer cells. Membrane-expressed ICOSL is determined as an independent prognostic factor for OS in breast cancer but without significantly correlating with other clinicopathologic parameters such as age, menopausal status, depth of invasion, lymph node metastasis status, histologic classification, etc. Conclusion Our study suggests that the up-regulated expression of ICOSL protein in breast tumor cells can be associated with poor prognoses in invasive breast carcinomas.

Expression Patterns of ER, HER2, and NM23-H1 in Breast Cancer Patients with Different Menopausal Status

2011 ◽  
Vol 15 (4) ◽  
pp. 211-219 ◽  
Author(s):  
Su-Wei Dong ◽  
Lin Wang ◽  
Jun Sui ◽  
Xi-Yun Deng ◽  
Xiao-Dan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Expression Patterns ◽  
Menopausal Status ◽  
Breast Cancer Patients

scholarly journals Expression of the Androgen Receptor and its Correlation with Molecular Subtypes in 980 Chinese Breast Cancer Patients

2011 ◽  
Vol 6 ◽  
pp. BCBCR.S8323 ◽  
Author(s):  
Ji-ping Qi ◽  
You-lin Yang ◽  
Hong Zhu ◽  
Jianmin Wang ◽  
Ying Jia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Therapeutic Target ◽  
Expression Patterns ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Potential Therapeutic Target ◽  
Ki 67 ◽  
Er Positive

Background Recent studies have shown that androgen displays an inhibitory effect on breast cancer cell lines that express androgen receptor (AR) but not estrogen receptor (ER) and progesterone receptor (PR). We have previously reported that approximately 1/3 of ER negative high grade invasive ductal carcinomas express AR. Thus, AR can serve as a potential therapeutic target for this group of patients. Aim Here we investigated AR expression patterns in 980 consecutive breast carcinomas. Results We found that (1) AR was expressed more frequently (77%) than ER (61%) and PR (60%) in breast carcinomas; (2) AR expression was associated with ER and PR expression ( P < 0.0001), small tumor size ( P = 0.0324) and lower Ki-67 expression ( P = 0.0013); (3) AR expression was found in 65% of ER negative tumors; (4) AR expression was associated with PR and Ki-67 in ER negative tumors, but not in ER positive tumors; (5) AR expression was higher in ER positive subtypes (Luminal A, Luminal B and Luminal HER2 subtypes, 80%-86%) and lower in ER negative subtypes [HER2, triple negative (TN), and TN EFGR positive subtypes; 52%-66%], with over 50% of TN tumors expressing AR. Conclusion More breast carcinomas express AR than ER and PR, including significant numbers of ER negative and TN tumors, for which AR could serve as a potential therapeutic target.

scholarly journals Aberrant expression of E-cadherin in infiltrating ductal and lobular breast carcinomas and its correlation with clinicopathological parameters – A hospital-based study

2021 ◽  
Vol 7 (3) ◽  
pp. 99-109
Author(s):  
Shruthi T ◽  
◽  
Dr. Ramesh Chavan ◽  
Dr. Naresh Jaikumar Kulkarni ◽  
◽  
...  
Keyword(s):  
Lobular Carcinoma ◽  
Surgical Margin ◽  
Clinicopathological Parameters ◽  
Breast Carcinomas ◽  
Malignant Tumours ◽  
Aberrant Expression ◽  
Retrieval Method ◽  
Calcium Dependent ◽  
Ductal Carcinomas ◽  
E Cadherin

Introduction: Breast carcinoma is one of the commonest malignant tumours in women, leading topremature deaths and morbidity. E-cadherin is a 120kDa calcium-dependent transmembraneglycoprotein encoded by the CDH1 gene located on chromosome 16q21 and is expressed in mostepithelial cells. Loss of E Cadherin expression implies cell discohesion and favours metastasis.Materials and Methods: A total of 30 cases of breast carcinomas were studied, over two years.Histological grade and type were assessed by staining the paraffin-embedded sections with H & E.Using IHC technique, E-cadherin antigen was retrieved by Heat-Induced Epitome Retrieval method,and immunostaining was scored semiquantitatively. Cases were grouped as ‘preserved,’ whenpositivity was strong membranous, and occurred in more than 75% of the neoplastic epithelial cellsand ‘aberrant’ in all the remaining cases. Results: E-cadherin was found to be preserved in 46.7%of all the breast carcinomas and aberrant in 51.7% of invasive ductal carcinomas (IDC) alone, while100% of invasive lobular carcinomas showed aberrant expression. No significant correlation wasfound with E-cadherin grading and histological type of carcinoma, histopathological grade orinvolvement of deep surgical margin. Conclusion: Differentiation between invasive ductal andinvasive lobular carcinoma based on the loss of E-cadherin has to be done cautiously given itsaberrant expression in ductal carcinomas as well.

scholarly journals Impact of Epithelial–Mesenchymal Transition on the Immune Landscape in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5099
Author(s):  
Fatima-Zohra Khadri ◽  
Marianne Samir Makboul Issac ◽  
Louis Arthur Gaboury
Keyword(s):  
Breast Cancer ◽  
Inflammatory Infiltrate ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Clinicopathological Parameters ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Cancer Tumor ◽  
The Impact ◽  
E Cadherin

The impact of epithelial–mesenchymal transition (EMT) signature on the immune infiltrate present in the breast cancer tumor microenvironment (TME) is still poorly understood. Since there is mounting interest in the use of immunotherapy for the treatment of subsets of breast cancer patients, it is of major importance to understand the fundamental tumor characteristics which dictate the inter-tumor heterogeneity in immune landscapes. We aimed to assess the impact of EMT-related markers on the nature and magnitude of the inflammatory infiltrate present in breast cancer TME and their association with the clinicopathological parameters. Tissue microarrays were constructed from 144 formalin-fixed paraffin-embedded invasive breast cancer tumor samples. The protein expression patterns of Snail, Twist, ZEB1, N-cadherin, Vimentin, GRHL2, E-cadherin, and EpCAM were examined by immunohistochemistry (IHC). The inflammatory infiltrate in the TME was assessed semi-quantitatively on hematoxylin and eosin (H&E)-stained whole sections and was characterized using IHC. The inflammatory infiltrate was more intense in poorly differentiated carcinomas and triple-negative carcinomas in which the expression of E-cadherin and GRHL2 was reduced, while EpCAM was overexpressed. Most EMT-related markers correlated with plasma cell infiltration of the TME. Taken together, our findings reveal that the EMT signature might impact the immune response in the TME.

scholarly journals L1CAM Expression in Recurrent Estrogen Positive/HER2 Negative Breast Cancer

2020 ◽  
Author(s):  
Ioana Moisini ◽  
Huina Zhang ◽  
Marcus D’Aguiar ◽  
David G. Hicks ◽  
Bradley M. Turner
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Lymph Node Status ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Er Positive ◽  
L1cam Expression

Abstract Background: We investigate L1CAM expression in ER positive/HER2 negative breast carcinomas. The finding of a potential correlation between high L1CAM expression and recurrent/metastatic disease in luminal A and B breast carcinomas may be helpful for risk stratification and open opportunities for targeted therapies.Methods: 304 cases comprising 152 cases of ER positive, PR positive/negative and HER2 negative recurrent/metastatic breast carcinomas and 152 non-recurrent controls were included. ER, PR, HER-2, Ki-67 status, Nottingham grade, tumor size, tumor stage, number of foci, lymph node status, lymphovascular invasion, phenotype, laterality, age at diagnosis and first distant or local recurrence were recorded. Results: L1CAM positive cases showed increased specificity for recurrence and these patients were significantly younger than L1CAM negative ones. Compared to L1CAM negative recurrent cases, L1CAM positive ones had a noticeably higher Ki-67, tended to be larger and recurred sooner. All L1CAM positive recurrent/metastatic cases were of the luminal B subtype compared to 67.3% of the L1CAM negative cases. Conclusions: L1CAM is highly specific for recurrence in a subset of breast cancer patients and may be associated with more aggressive behavior, particularly in luminal B breast cancers with higher Ki-67 expression. Further investigation about the prognostic value of L1CAM is warranted.

The predictive potential of Neuronatin for neoadjuvant chemotherapy of breast cancer

2021 ◽  
pp. 1-13
Author(s):  
Willi Pieper ◽  
Atanas Ignatov ◽  
Thomas Kalinski ◽  
Johannes Haybaeck ◽  
Piotr Czapiewski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Biomarker ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Cytopathic Effects

BACKGROUND: Neuronatin (NNAT) determined by immunohistochemistry is a negative prognostic biomarker for breast cancer, independent of the major clinicopathological markers. OBJECTIVE: Here, we investigated whether NNAT is also a predictive biomarker for pathological remission after neoadjuvant chemotherapy. METHODS : One hundred and four breast cancer patients, treated with systemic neoadjuvant chemotherapy were included in this retrospective study. NNAT was detected in formaldehyde fixed, paraffin embedded primary cancer tissue by immunohistochemistry and an immuno-reactive score (IRS) determined. Pathological remission was scored according to Sinn and by evaluation of cytopathic effects. NNAT-IRS was correlated with clinicopathological parameters as well as relapse free and overall survival and for pathological remission after neoadjuvant therapy. RESULTS: NNAT IRS was an independent prognostic marker for relapse free and overall survival and the time from diagnosis to the “tumor-free” state. NNAT IRS was associated with Luminal-A tumors and correlated slightly negative with age and lymph-node metastasis. There was no significant correlation of NNAT-IRS with Sinn’s remission score, but with cytopathic effects of chemotherapy. CONCLUSIONS: We confirmed the prognostic impact of NNAT-IRS in an independent cohort of neoadjuvantly treated patients. Additionally, a correlation with a score for pathological remission under systemic neoadjuvant chemotherapy for breast cancer was found.

Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers

2020 ◽  
Vol 21 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Prasuja Rokkam ◽  
Shailender Gugalavath ◽  
Deepak Kakara Gift Kumar ◽  
Rahul Kumar Vempati ◽  
Rama Rao Malla
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Neural Development ◽  
Splice Variants ◽  
Metastatic Breast ◽  
Basic Function ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Cellular Processes

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

scholarly journals Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3366
Author(s):  
Anna-Sophie Liegmann ◽  
Kerstin Heselmeyer-Haddad ◽  
Annette Lischka ◽  
Daniela Hirsch ◽  
Wei-Dong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Genome Instability ◽  
Single Cells ◽  
Gene Mutations ◽  
Intratumor Heterogeneity ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Pik3ca Mutations

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.

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