Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul.
Molecular Pathology Area, School of Dentistry, Universidad de La Republica (UDELAR), Montevideo, Uruguay.
Appl Immunohistochem Mol Morphol. 2021;29(5):366-373. doi: 10.1097/PAI.0000000000000874.
Odontogenic lesions (OL) are an important group of oral and maxillofacial diseases represented by odontogenic cysts, benign, and malignant tumors. The brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling pathway has multiple biological actions and has been identified as an important pathway in the proliferation, invasion, and survival of different epithelial tumors. Its role in the development of OL, however, has so far been unexplored. Our aim was to evaluate the BDNF/TrkB/Akt/p-RPS6 signaling pathway in OL of epithelial origin. This cross-sectional study comprised 3 cases of tooth germs, 25 cases of odontogenic keratocyst (OK), 29 cases of ameloblastoma (Am), and 6 cases of ameloblastic carcinoma. Immunohistochemical staining for BDNF, TrkB, p-Akt, and p-RPS6 was performed. OLs were evaluated according to the pattern of immunohistochemical expression in epithelial cells and by semiquantitative scores that considered the intensity of staining and percentage of positive cells. BDNF stromal expression was also assessed. No significant differences were observed with respect to the percentage of positive cases for all markers. Regarding the immunoreactive scores, BDNF and p-RPS6 expressions were similar in the odontogenic epithelium of all OL. However, TrkB and p-Akt were overexpressed in OK compared with ameloblastic carcinoma. In Am, epithelial BDNF was significantly higher compared with stromal expression. In conclusion, BDNF seems to participate in the development of cystic, benign, and malignant odontogenic epithelium to similar degrees. The acquisition of the invasive or malignant phenotype in odontogenic neoplasms is not associated with alterations in the BDNF/TrkB/Akt/RPS6 axis, which could be implicated in the differentiation process.
牙源性病变（OL）是一组重要的口腔颌面部疾病，包括牙源性囊肿、良性和恶性肿瘤。脑源性神经营养因子（BDNF）/原肌球蛋白受体激酶 B（TrkB）信号通路具有多种生物学作用，已被确定为不同上皮肿瘤增殖、侵袭和存活的重要途径。然而，其在 OL 发生发展中的作用尚未得到探索。我们的目的是评估上皮源性 OL 中的 BDNF/TrkB/Akt/p-RPS6 信号通路。本横断面研究包括 3 例牙胚、25 例牙源性角化囊肿（OKC）、29 例成釉细胞瘤（Am）和 6 例成釉细胞瘤。进行 BDNF、TrkB、p-Akt 和 p-RPS6 的免疫组织化学染色。根据上皮细胞免疫组织化学表达模式和考虑染色强度和阳性细胞百分比的半定量评分评估 OL。还评估了 BDNF 基质表达。所有标志物的阳性病例百分比均无显著差异。关于免疫反应性评分，所有 OL 的牙源性上皮中 BDNF 和 p-RPS6 的表达相似。然而，TrkB 和 p-Akt 在 OKC 中的表达高于 ameloblastic carcinoma。在 Am 中，上皮 BDNF 明显高于基质表达。总之，BDNF 似乎参与了囊性、良性和恶性牙源性上皮的发育，程度相似。牙源性肿瘤获得侵袭性或恶性表型与 BDNF/TrkB/Akt/RPS6 轴的改变无关，该轴可能与分化过程有关。
