title: Small oral squamous cell carcinomas with nodal lymphogenic metastasis show increased infiltration of M2 polarized macrophages--an immunohistochemical analysis.
abstract: BACKGROUND
  In solid malignancies the influence of immunological parameters - especially of macrophages - on invasiveness, metastatic potential and prognosis has been shown. There are no studies quantitatively analysing the macrophage polarization in oral squamous cell carcinoma (oscc). The aim of this study was to correlate macrophage polarization in the epithelial and stromal compartment of oscc with histopathologic parameters.
  
  
  METHODS
  T1 and T2 oscc samples (n = 34) were used. Automated immunohistochemical staining detected CD68, CD11c, CD163 and MRC1 positive cells. All samples were completely digitalized using whole slide imaging and the number of stained cells per area was assessed quantitatively.
  
  
  RESULTS
  Primary tumours with lymphogenic metastasis (N+) showed a significantly (p < 0.05) increased count of CD68, CD11c, CD163 and MRC1 positive cells in the epithelial fraction compared to N0 tumours. The ratio of CD163 positive cells (M2 macrophages) to CD68 positive cells (M1 and M2 macrophages) was significantly (p < 0.05) increased in N+ tumours.
  
  
  CONCLUSIONS
  An increased macrophage infiltration and an increased M2 polarization in primary oral squamous cell carcinomas with lymphogenic metastasis was shown. Macrophages that migrated into the epithelial tumour fraction seem to be of special biological importance. The results indicate a central role of macrophages in the progression of oscc.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Germany. Electronic address: manuel.weber@uk-erlangen.de.
authors.forename: Manuel
authors.initials: M
authors.lastname: Weber
authors.affiliation: Institute of Pathology, Department of Nephropathology, University of Erlangen-Nuremberg, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Büttner-Herold
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hyckel
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Moebius
authors.affiliation: Department of Radiation Oncology, University of Erlangen-Nuremberg, Germany.
authors.forename: Luitpold
authors.initials: L
authors.lastname: Distel
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Ries
authors.affiliation: Institute of Pathology, Department of Nephropathology, University of Erlangen-Nuremberg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Germany.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Neukam
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Wehrhan
mesh_terms: D000539:Alveolar Process / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary; D002452:Cell Count; D016764:Cell Polarity / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D003238:Connective Tissue / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009060:Mouth Floor / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011956:Receptors, Cell Surface / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis; D051116:Receptors, Scavenger / Q000032:analysis; D014062:Tongue Neoplasms / Q000473:pathology; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039521:CD11c Antigen; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C573543:MRC1 protein, human
keywords: M1; M2; Macrophage polarization; Oral cancer; Oral squamous cell carcinoma; oscc