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Open Access Highly Accessed Research article

Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes – an immunohistochemical study

Falk Wehrhan1, Maike Büttner-Herold2, Peter Hyckel3, Patrick Moebius1, Raimund Preidl1, Luitpold Distel4, Jutta Ries1, Kerstin Amann2, Christian Schmitt1, Friedrich W Neukam1 and Manuel Weber1*

Author Affiliations

1 Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Glueckstrasse 11, 91054 Erlangen, Germany

2 Institute of Pathology, Department of Nephropathology, Friedrich-Alexander University Erlangen-Nürnberg, Krankenhausstraße 12, 91054 Erlangen, Germany

3 Department of Oral and Maxillofacial Surgery, University of Jena, Erlanger Allee 101, 07749 Jena, Germany

4 Department of Radiation Oncology, Friedrich-Alexander University Erlangen-Nürnberg, Universitätsstraße 27, 91054 Erlangen, Germany

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BMC Cancer 2014, 14:522  doi:10.1186/1471-2407-14-522

Published: 21 July 2014



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).


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.


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.


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.

Oral squamous cell carcinoma; Oral cancer; Lymph node; Macrophage polarization; Peripheral tolerance; oscc; M1; M2