title: Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma.
abstract: BACKGROUND
  The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients.
  
  
  METHODS
  Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for SOX2, NANOG and OCT4 gene expression by real-time PCR.
  
  
  RESULTS
  SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432).
  
  
  CONCLUSIONS
  In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.
authors.affiliation: University of Tuebingen Medical Center II, Otfried-Mueller-Strasse 10, 72076 Tuebingen, Germany. claudia.lengerke@med.uni-tuebingen.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Lengerke
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Ralf
authors.initials: R
authors.lastname: Kurth
authors.forename: Hans
authors.initials: H
authors.lastname: Neubauer
authors.forename: Veit
authors.initials: V
authors.lastname: Scheble
authors.forename: Friederike
authors.initials: F
authors.lastname: Müller
authors.forename: Friederike
authors.initials: F
authors.lastname: Schneider
authors.forename: Karen
authors.initials: K
authors.lastname: Petersen
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Petra M
authors.initials: PM
authors.lastname: Bareiss
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005784:Gene Amplification; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009367:Neoplasm Staging; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D055748:SOXB1 Transcription Factors