title: In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer.
abstract: Tumor surgery is aimed at complete resection of the lesion while ensuring a sufficient tumor-specific safety distance. Nevertheless, in many cases the most peripheral part - the invasion front - remains in situ. Tumor cells at the tumor margin have been reported to lose their epithelial properties and acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal transition (EMT) is believed to be of prime importance for tissue and vessel invasion. Furthermore, the detection of tumor-infiltrating lymphocytes in the microenvironment of breast cancer might serve as a reliable prognostic marker.
  
  
  
  We investigated tissue microarrays of 352 breast cancer patients with regard to the presence and distribution of the EMT factor Snail, and the presence of FoxP3, CD3 and CD8 in the immune microenvironment.
  
  
  
  The expression of the transcription factor Snail is strongly associated with longer disease-free and overall survival. The presence of CD3, CD8 or FoxP3 is associated with a better outcome, although statistically significant results were noted only for FoxP3. The prognostic significance of FoxP3 and Snail were also proven in multivariate analysis.
  
  
  
  Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein, Campus Kiel, Germany. Electronic address: kiel.school@uksh.de.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Alkatout
authors.affiliation: Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Hübner
authors.affiliation: Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Antonia
authors.initials: A
authors.lastname: Wenners
authors.affiliation: Institute of Medical Informatics and Statistics, University Hospitals Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hedderich
authors.affiliation: Department of Radiology and Neuroradiology, Klinikum Dortmund, Dortmund, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Wiedermann
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, and Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez
authors.affiliation: Department of Pathology, General Pathology and Hematopathology, University Hospitals Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Department of Pathology, General Pathology and Hematopathology, University Hospitals Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Micaela
authors.initials: M
authors.lastname: Mathiak
authors.affiliation: Department of Gynecology and Obstetrics, University Hospitals Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.affiliation: Department of Pathology, General Pathology and Hematopathology, University Hospitals Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005819:Genetic Markers; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012959:Socioeconomic Factors; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D017252:CD3 Complex; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D000071250:Snail Family Transcription Factors
keywords: Breast cancer; CD3; CD8; Epithelial-to-mesenchymal transition; FoxP3; Microenvironment; Prognostic factor; Snail; Tissue microarray; Tumor heterogeneity