Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor

2016 ◽  
Vol 70 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Karama Asleh-Aburaya ◽  
Brandon S Sheffield ◽  
Zuzana Kos ◽  
Jennifer R Won ◽  
Xiu Q Wang ◽  
...  
2006 ◽  
Vol 95 (3) ◽  
pp. 339-346 ◽  
Author(s):  
P Surowiak ◽  
V Materna ◽  
B Györffy ◽  
R Matkowski ◽  
A Wojnar ◽  
...  

1999 ◽  
Vol 81 (6) ◽  
pp. 1042-1051 ◽  
Author(s):  
M Brimmell ◽  
J S Burns ◽  
P Munson ◽  
L McDonald ◽  
M J O’Hare ◽  
...  

Breast cancer is the commonest cancer in women worldwide and represents a highly heterogeneous group of tumours particularly in terms of molecular features, prognosis and response to therapy. Breast cancer molecular classification can predict the prognosis of breast cancer in terms of recurrence and help and guide us regarding the treatment decision about systemic therapy. Breast carcinomas may be stratified into subtypes similar to those defined by Gene expression profiling using a panel of immune-histochemical (IHC) markers. Routine IHC evaluations of breast cancers may, therefore, provide a reasonable alternative to costly genetic assays especially in under-resourced healthcare systems. The purpose of this study is to investigate the prevalence of molecular subtypes and correlate it to clinic-pathological features. Methods: From 2005 to 2017 total of 4847 Breast cancer patients, in whom complete information was available to classify them into luminal subtypes were retrieved and classified into intrinsic subtypes and patients information in each type was collected about age, tumour size, stage, grade and nodal status. Results: In luminal classification, a highly significant difference was found in mean age (p<0.001) tumour size (p<0.001), grade, metastasis and Ki67. The statistical significance of Her 2 positive and triple negative was found with stage, grade, metastasis and Ki67. Conclusions: IHC assignment into Luminal subtypes is clinically informative in our patients and routinely using this in our practice could identify patients that may need a more aggressive treatment to reduce the likelihood of recurrences.


2018 ◽  
Author(s):  
Daniel L. Roden ◽  
Laura A. Baker ◽  
Benjamin Elsworth ◽  
Chia-Ling Chan ◽  
Kate Harvey ◽  
...  

AbstractBreast cancer has long been classified into a number of molecular subtypes that predict prognosis and therefore influence clinical treatment decisions. Cellular heterogeneity is also evident in breast cancers and plays a key role in the development, evolution and metastatic progression of many cancers. How clinical heterogeneity relates to cellular heterogeneity is poorly understood, so we approached this question using single cell gene expression analysis of well established in vitro and in vivo models of disease.To explore the cellular heterogeneity in breast cancer we first examined a panel of genes that define the PAM50 classifier of molecular subtype. Five breast cancer cell line models (MCF7, BT474, SKBR3, MDA-MB-231, and MDA-MB-468) were selected as representatives of the intrinsic molecular subtypes (luminal A and B, basal-like, and Her2-enriched). Single cell multiplex RT-PCR was used to isolate and quantify the gene expression of single cells from each of these models, and the PAM50 classifier applied. Using this approach, we identified heterogeneity of intrinsic subtypes at single-cell level, indicating that cells with different subtypes exist within a cell line. Using the Chromium 10X system, this study was extended into thousands of cells from the MCF7 cell-line and an ER+ patient derived xenograft (PDX) model and again identified significant intra-tumour heterogeneity of molecular subtype.Estrogen Receptor (ER) is an important driver and therapeutic target in many breast cancers. It is heterogeneously expressed in a proportion of clinical cases but the significance of this to ER activity is unknown. Significant heterogeneity in the transcriptional activation of ER regulated genes was observed within tumours. This differential activation of the ER cistrome aligned with expression of two known transcriptional co-regulatory factors of ER (FOXA1 and PGR).To examine the degree of heterogeneity for other important phenotypic traits, we used an unsupervised clustering approach to identify cellular sub-populations with diverse cancer associated transcriptional properties, such as: proliferation; hypoxia; and treatment resistance. In particular, we show that we can identify two distinct sub-populations of cells that may have denovo resistance to endocrine therapies in a treatment naïve PDX model of ER+ breast cancer. One of these consists of cells with a non-proliferative transcriptional phenotype that is enriched for transcriptional properties of ERBB2 tumours. The other is heavily enriched for components of the primary cilia. Gene regulatory networks were used to identify transcription factor regulons that are active in each cell, leading us to identify potential transcriptional drivers (such as E2F7, MYB and RFX3) of the cilia associated endocrine resistant cells. This rare subpopulation of cells also has a highly heterogenous mix of intrinsic subtypes highlighting a potential role of intra-tumour subtype heterogeneity in endocrine resistance and metastatic potential.Overall, These results suggest a high degree of cellular heterogeneity within breast cancer models, even cell lines, that can be functionally dissected into sub-populations of cells with transcriptional phenotypes of potential clinical relevance.


2019 ◽  
Vol 475 (2) ◽  
pp. 151-162 ◽  
Author(s):  
Stina Garvin ◽  
Eva Vikhe Patil ◽  
Lars-Gunnar Arnesson ◽  
Husam Oda ◽  
Elham Hedayati ◽  
...  

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