title: Prognostic significance of macrophage polarization in early stage oral squamous cell carcinomas.
abstract: BACKGROUND
  Polarization of tumor infiltrating macrophages is associated with the prognosis of solid malignancies and correlates with the occurrence of lymph node metastases in oral squamous cell carcinomas (oscc). Early stage (T1/T2, N0) oscc are characterized by a good prognosis and can be cured by surgery. The postoperative regime usually contains no adjuvant radio-/chemotherapy. The current pilot study was conducted to elucidate whether macrophage polarization in tumor resection specimens and diagnostic biopsies of early stage oscc is associated with tumor outcome.
  
  
  METHODS
  Patients with T1/T2, N0, and R0>5mm oscc without adjuvant therapy and 3-year follow-up after tumor resection were retrospectively selected. Tissue microarrays (TMA) containing diagnostic biopsies (n=17) and tumor resection specimens (n=17) were processed for immunohistochemistry in this pilot study to detect CD68-, CD11c-, CD163- and MRC1-positive macrophages. Samples were digitized, and the expression of macrophage markers was quantitatively analyzed.
  
  
  RESULTS
  High infiltration of M2 polarized macrophages correlated with poor tumor outcome in early stage (T1/T2, N0) oscc. This correlation was observed in tumor resection specimens, but was also observed in diagnostic biopsies. M2 macrophage polarization in biopsies - but not in tumor resection samples - correlated with high scores in tumor grading.
  
  
  CONCLUSIONS
  Macrophage polarization in early stage oscc is a potential prognostic marker for tumor outcome. The correlation of M2 polarized macrophages with tumor outcome can already be detected in the initial biopsies. Furthermore, M2 polarization of macrophages in biopsies is associated with an increased dedifferentiation.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. Electronic address: manuel.weber@uk-erlangen.de.
authors.forename: Manuel
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Iliopoulos
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Moebius
authors.affiliation: Institute of Pathology, Department of Nephropathology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Büttner-Herold
authors.affiliation: Institute of Pathology, Department of Nephropathology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Ries
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Preidl
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Neukam
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Wehrhan
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000473:pathology*; D008562:Membrane Glycoproteins; D009062:Mouth Neoplasms / Q000473:pathology*; D010865:Pilot Projects; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D039521:CD11c Antigen; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C573543:MRC1 protein, human
keywords: Biopsy; M1; M2; Macrophage polarization; Oral cancer; Oral squamous cell carcinoma; Oscc; Prognosis; TMA; Tumor outcome