title: Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes - an immunohistochemical study.
abstract: BACKGROUND
  It is largely accepted that specific immunological parameters in solid malignancies are associated with patient's prognosis. Recently a correlation of macrophage polarization with histomorphological parameters could also be shown in oral squamous cell carcinoma (oscc). The observed tumor derived peripheral immune tolerance could be associated with the macrophage polarization in regional tumor draining lymph nodes.So far there are no studies analyzing the macrophage polarization in cervical lymph nodes of oscc patients. In the present study we aimed to correlate macrophage polarization in different anatomical lymph node compartments of patients diagnosed with oscc with histopathologic parameters of the primary tumor (T-, N-, L-, V-, Pn-status, grading).
  
  
  METHODS
  Tumor free (n = 37) and metastatic (n = 17) lymph nodes of T1 and T2 oscc patients were processed for immunohistochemistry to detect CD68, CD11c, CD163 and MRC1 positive cells. Samples were digitized using whole slide imaging and the number of cells expressing the aforementioned markers in the region of interest quantitatively analyzed.
  
  
  RESULTS
  The malignancy of the primary tumor (defined by T-, L-, Pn-status, grading) correlated with the lymph node macrophage polarization. L1 and Pn1 tumor cases displayed a significantly (p < 0.05) decreased M1 and increased M2 polarization in the sinus of the lymph nodes. G3 cases presented a significantly (p < 0.05) increased M2 polarization in the sinus compared to G2 cases. T2 tumors had significantly (p < 0.05) increased M2 polarization in the interfollicular zone of regional lymph nodes compared to T1 tumors. Metastatic and non-metastatic lymph nodes did not differ regarding their macrophage polarization.
  
  
  CONCLUSIONS
  The current study revealed for the first time an influence of oscc on the macrophage polarization in regional lymph nodes. Markers of malignant behavior in the primary tumor were associated with a shift of macrophage polarization in lymph nodes from the anti-tumoral M1 type to the tumor-promoting M2 type. As tumor free and metastatic lymph nodes did not differ in terms of their macrophage polarization pattern, there must be other factors influencing the location for lymph node metastasis formation.
authors.forename: Falk
authors.initials: F
authors.lastname: Wehrhan
authors.forename: Maike
authors.initials: M
authors.lastname: Büttner-Herold
authors.forename: Peter
authors.initials: P
authors.lastname: Hyckel
authors.forename: Patrick
authors.initials: P
authors.lastname: Moebius
authors.forename: Raimund
authors.initials: R
authors.lastname: Preidl
authors.forename: Luitpold
authors.initials: L
authors.lastname: Distel
authors.forename: Jutta
authors.initials: J
authors.lastname: Ries
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Christian
authors.initials: C
authors.lastname: Schmitt
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Neukam
authors.affiliation: Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Glueckstrasse 11, 91054 Erlangen, Germany. manuel.weber@uk-erlangen.de.
authors.forename: Manuel
authors.initials: M
authors.lastname: Weber
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology* / Q000473:pathology