Header

UZH-Logo

Maintenance Infos

Differential expression of epithelial-mesenchymal transition and stem cell markers in intrinsic subtypes of breast cancer


Pomp, Victoria; Leo, Cornelia; Mauracher, Andrea; Korol, Dimitri; Guo, Wenjun; Varga, Zsuzsanna (2015). Differential expression of epithelial-mesenchymal transition and stem cell markers in intrinsic subtypes of breast cancer. Breast Cancer Research and Treatment, 154(1):45-55.

Abstract

The transcription factors SLUG and SOX9 have been shown to define mammary stem cell state. Similarly, epithelial-mesenchymal transition (EMT) markers (E-Cadherin, mTOR) have been shown to play a role in tumor-progression and metastatic potential in breast cancer. Finally, SOX10 is known to be expressed in breast cancer as well. The overexpressions of EMT and stem cell markers have been shown to correlate with poor overall survival. In this study, we examined whether the expression of these markers correlates with intrinsic subtypes of breast cancer and whether there is a prognostic difference in their expression-profile. We analyzed 617 breast cancer samples from two tissue micro arrays. Breast cancer samples were categorized into three groups according to hormone receptor expression and HER2-status as Luminal A/B, HER2-positive, and triple negative subgroup. Immunohistochemical expressions of SLUG, SOX9, SOX10, E-Cadherin, and mTOR were semi-quantitatively analyzed using a two-tiered and three-tiered scoring system in which cytoplasmic and nuclear stains were considered. Strong nuclear expression of SLUG was observed preferentially in triple negative but not in Luminal A/B or HER2-positive cases (24 vs. 3 and 0 %, p < 0.001). Loss of SOX9 in the nuclear stain was less frequent in triple negative than in Luminal A/B or HER2-positive cases (4 vs. 9 vs. 13 %, p < 0.001). Expression of nuclear SOX10 was lower in triple negative than in Luminal A/B and HER2-positive cases (67 vs.78 and 79 %, p = 0.012). E-Cadherin loss was observed only in Luminal A/B tumors (p = 0.016), no difference in the mTOR expression was seen between any of the three groups. No correlation to conventional histopathological-parameters or stage could be established in our cohort. Our study shows an inversed preferential nuclear expression of SLUG, SOX10, and SOX9 in triple negative and non-triple negative cases. This information is important in understanding the biology of triple negative breast cancer, also in terms of future studies dealing with targeted therapies based on the alterations of EMT and stem cell markers.

Abstract

The transcription factors SLUG and SOX9 have been shown to define mammary stem cell state. Similarly, epithelial-mesenchymal transition (EMT) markers (E-Cadherin, mTOR) have been shown to play a role in tumor-progression and metastatic potential in breast cancer. Finally, SOX10 is known to be expressed in breast cancer as well. The overexpressions of EMT and stem cell markers have been shown to correlate with poor overall survival. In this study, we examined whether the expression of these markers correlates with intrinsic subtypes of breast cancer and whether there is a prognostic difference in their expression-profile. We analyzed 617 breast cancer samples from two tissue micro arrays. Breast cancer samples were categorized into three groups according to hormone receptor expression and HER2-status as Luminal A/B, HER2-positive, and triple negative subgroup. Immunohistochemical expressions of SLUG, SOX9, SOX10, E-Cadherin, and mTOR were semi-quantitatively analyzed using a two-tiered and three-tiered scoring system in which cytoplasmic and nuclear stains were considered. Strong nuclear expression of SLUG was observed preferentially in triple negative but not in Luminal A/B or HER2-positive cases (24 vs. 3 and 0 %, p < 0.001). Loss of SOX9 in the nuclear stain was less frequent in triple negative than in Luminal A/B or HER2-positive cases (4 vs. 9 vs. 13 %, p < 0.001). Expression of nuclear SOX10 was lower in triple negative than in Luminal A/B and HER2-positive cases (67 vs.78 and 79 %, p = 0.012). E-Cadherin loss was observed only in Luminal A/B tumors (p = 0.016), no difference in the mTOR expression was seen between any of the three groups. No correlation to conventional histopathological-parameters or stage could be established in our cohort. Our study shows an inversed preferential nuclear expression of SLUG, SOX10, and SOX9 in triple negative and non-triple negative cases. This information is important in understanding the biology of triple negative breast cancer, also in terms of future studies dealing with targeted therapies based on the alterations of EMT and stem cell markers.

Statistics

Citations

5 citations in Web of Science®
6 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 30 Oct 2015
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:14 October 2015
Deposited On:30 Oct 2015 07:15
Last Modified:05 Apr 2016 19:28
Publisher:Springer
ISSN:0167-6806
Publisher DOI:https://doi.org/10.1007/s10549-015-3598-6
PubMed ID:26467042

Download

Preview Icon on Download
Content: Published Version
Filetype: PDF - Registered users only
Size: 6MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations