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

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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.

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Acknowledgments

The authors wish to thank to Mrs. Martina Storz for preparing the TMA sections, to Mr André Fitsche for performing all immunohistochemical stains and to Mr. André Wethmar and Mr Norbert Wey for preparing the high quality illustrations and performing the digitalization of the stained TMA slides.

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Authors and Affiliations

  1. Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland

    Victoria Pomp & Zsuzsanna Varga

  2. Department of Gynecology, Cantonal Hospital Baden, Baden, Switzerland

    Cornelia Leo

  3. University Children’s Hospital Zurich, Zurich, Switzerland

    Andrea Mauracher

  4. Cancer Registry, University Hospital Zurich, Zurich, Switzerland

    Dimitri Korol

  5. Ruth L and Davis S Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA

    Wenjun Guo

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  1. Victoria Pomp
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  6. Zsuzsanna Varga
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Correspondence to Zsuzsanna Varga.

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Pomp, V., Leo, C., Mauracher, A. et al. Differential expression of epithelial–mesenchymal transition and stem cell markers in intrinsic subtypes of breast cancer. Breast Cancer Res Treat 154, 45–55 (2015). https://doi.org/10.1007/s10549-015-3598-6

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  • DOI: https://doi.org/10.1007/s10549-015-3598-6

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