title: Differential expression of epithelial–mesenchymal transition and stem cell markers in intrinsic subtypes of breast cancer.
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.
authors.forename: Victoria
authors.initials: V
authors.lastname: Pomp
authors.forename: Cornelia
authors.initials: C
authors.lastname: Leo
authors.forename: Andrea
authors.initials: A
authors.lastname: Mauracher
authors.forename: Dimitri
authors.initials: D
authors.lastname: Korol
authors.forename: Wenjun
authors.initials: W
authors.lastname: Guo
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D055757:SOXE Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D000071250:Snail Family Transcription Factors; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D046888:Tissue Array Analysis / Q000379:methods; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D018719:Erb-b2 Receptor Tyrosine Kinases; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; D000071250:Snail Family Transcription Factors; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C000604407:SNAI1 protein, human; C527923:SOX10 protein, human; C527932:SOX9 protein, human; C546842:MTOR protein, human; C508053:ERBB2 protein, human