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.

中文翻译：

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口腔白斑的恶变与巨噬细胞极化有关。

背景技术大多数口腔鳞状细胞癌（OSCC）以口腔白斑（OLP）为基础发生。不典型增生的组织学程度不足以预测OLP恶性转化。免疫学参数对于癌症的预后评估和治疗越来越重要。M2极化的巨噬细胞显示与OSCC进展和不良预后有关。当前的研究旨在回答在5年内具有恶性转化为OSCC的OLP是否与没有转化的OLP在巨噬细胞浸润和极化方面有所不同。方法对201份标本（50份转化型OLP，53份非转化型OLP，49份相应的OSCC和49份健康的口腔粘膜对照）进行免疫组织化学处理。对样品进行CD68，CD163和CD11c表达染色，完全数字化并进行计算机辅助细胞计数。差异评估上皮和上皮下隔室。使用Mann-Whitney U检验对各组进行统计学比较。确定了用于区分转化和非转化OLP的临界点，并使用卡方检验（χ2检验）计算了巨噬细胞浸润和恶性转化之间的关联。结果与没有恶性转化的OLP相比，在5年内发生恶性转化的OLP中的巨噬细胞浸润和M2极化显着增加（p <0.05）。OSCC样品显示出最高的巨噬细胞浸润和最强的M2极化（p <0.05）。另外，转化的OLP显示巨噬细胞浸润向上皮区室转移（p <0.05）。χ2检验显示巨噬细胞浸润增加与恶性转化显着相关（p <0.05）。结论免疫学改变先于OLP恶性转化。巨噬细胞浸润增加和M2极化与OLP口腔癌的发展有关。巨噬细胞浸润可作为恶性转化的预测指标。