Malignant transformation of oral leukoplakia is associated with macrophage polarization
Abstract Background Most oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of c...
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doaj-b0f83a9922b24276bf149519fe3587262021-01-10T12:16:39ZengBMCJournal of Translational Medicine1479-58762020-01-0118111810.1186/s12967-019-02191-0Malignant transformation of oral leukoplakia is associated with macrophage polarizationManuel Weber0Falk Wehrhan1Christoph Baran2Abbas Agaimy3Maike Büttner-Herold4Hatice Öztürk5Kristina Neubauer6Claudia Wickenhauser7Marco Kesting8Jutta Ries9Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Department of Nephropathology, Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Institute of Pathology, Halle (Saale) University Hospital, Martin-Luther University Halle-Wittenberg (MLU)Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU)Abstract Background Most oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization. Methods 201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann–Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2 test). Results Macrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p < 0.05). OSCC samples showed the highest macrophage infiltration and strongest M2 polarization (p < 0.05). Additionally, transforming OLP revealed a significant shift of macrophage infiltration towards the epithelial compartment (p < 0.05). χ2 test revealed a significant association of increased macrophage infiltration with malignant transformation (p < 0.05). Conclusion Immunological changes precede malignant transformation of OLP. Increased macrophage infiltration and M2 polarization was associated with the development of oral cancer in OLP. Macrophage infiltration could serve as predictive marker for malignant transformation.https://doi.org/10.1186/s12967-019-02191-0Macrophage polarizationOral leukoplakiaM1M2CD68CD163 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Manuel Weber Falk Wehrhan Christoph Baran Abbas Agaimy Maike Büttner-Herold Hatice Öztürk Kristina Neubauer Claudia Wickenhauser Marco Kesting Jutta Ries |
spellingShingle |
Manuel Weber Falk Wehrhan Christoph Baran Abbas Agaimy Maike Büttner-Herold Hatice Öztürk Kristina Neubauer Claudia Wickenhauser Marco Kesting Jutta Ries Malignant transformation of oral leukoplakia is associated with macrophage polarization Journal of Translational Medicine Macrophage polarization Oral leukoplakia M1 M2 CD68 CD163 |
author_facet |
Manuel Weber Falk Wehrhan Christoph Baran Abbas Agaimy Maike Büttner-Herold Hatice Öztürk Kristina Neubauer Claudia Wickenhauser Marco Kesting Jutta Ries |
author_sort |
Manuel Weber |
title |
Malignant transformation of oral leukoplakia is associated with macrophage polarization |
title_short |
Malignant transformation of oral leukoplakia is associated with macrophage polarization |
title_full |
Malignant transformation of oral leukoplakia is associated with macrophage polarization |
title_fullStr |
Malignant transformation of oral leukoplakia is associated with macrophage polarization |
title_full_unstemmed |
Malignant transformation of oral leukoplakia is associated with macrophage polarization |
title_sort |
malignant transformation of oral leukoplakia is associated with macrophage polarization |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2020-01-01 |
description |
Abstract Background Most oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization. Methods 201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann–Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2 test). Results Macrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p < 0.05). OSCC samples showed the highest macrophage infiltration and strongest M2 polarization (p < 0.05). Additionally, transforming OLP revealed a significant shift of macrophage infiltration towards the epithelial compartment (p < 0.05). χ2 test revealed a significant association of increased macrophage infiltration with malignant transformation (p < 0.05). Conclusion Immunological changes precede malignant transformation of OLP. Increased macrophage infiltration and M2 polarization was associated with the development of oral cancer in OLP. Macrophage infiltration could serve as predictive marker for malignant transformation. |
topic |
Macrophage polarization Oral leukoplakia M1 M2 CD68 CD163 |
url |
https://doi.org/10.1186/s12967-019-02191-0 |
work_keys_str_mv |
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