Malignant transformation of oral leukoplakia is associated with macrophage polarization
Malignant transformation of oral leukoplakia is associated with macrophage polarization
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DOI：
10.1186/s12967-019-02191-0
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发表时间：
2020-01-07
影响因子：
7.4
通讯作者：
Ries, Jutta
中科院分区：
文献类型：
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作者：
Weber, Manuel;Wehrhan, Falk;Ries, Jutta
背景：大多数口腔鳞状细胞癌（OSCC）发生在口腔白斑（OLP）的基础上。不典型增生的组织学程度不足以预测OLP恶变。免疫学参数对于癌症的预后评估和治疗越来越重要。M2极化的巨噬细胞被证明与OSCC进展和较差的预后相关。本研究旨在回答以下问题：在巨噬细胞浸润和极化方面，5年内恶变为OSCC的OLP与未恶变的OLP是否不同。方法对201例口腔扁平苔藓标本（转化型50例，非转化型53例，口腔鳞癌49例，正常口腔黏膜49例）进行免疫组化检测。对样本进行CD 68、CD 163和CD 11 c表达染色，完全数字化并进行计算机辅助细胞计数。对上皮和上皮下室进行了差异评估。使用Mann-Whitney U检验对各组进行统计学比较。确定区分转化型和非转化型OLP的临界点，并使用卡方检验（卡方检验）计算巨噬细胞浸润和恶性转化之间的关联。结果5年内恶变组巨噬细胞浸润和M2极化明显高于未恶变组（p < 0.05）。OSCC样本显示最高的巨噬细胞浸润和最强的M2极化（p < 0.05）。此外，转化OLP显示巨噬细胞浸润向上皮区室的显著转移（p < 0.05）。经χ 2检验，巨噬细胞浸润与肿瘤恶变有显著相关性（P < 0.05）。结论OLP恶变前存在免疫学改变。巨噬细胞浸润和M2极化的增加与OLP中口腔癌的发展相关。巨噬细胞浸润可作为恶性转化的预测指标。
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 (chi(2) 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). chi(2) 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.