Department of Pathology and Oral Medicine Faculty of Dentistry, Universidad de Chile Calle Sergio Livingstone 943, Independencia, Santiago, Chile
Med Oral Patol Oral Cir Bucal. 2021 Nov 1;26(6):e729-e737. doi: 10.4317/medoral.24528.
Oral cancer represents the sixth most common cancer in the world and is associated with 40-50% survival at 5 years. Within oral malignancies, oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, which, according to histopathological criteria, are referred to as oral dysplasia and their diagnosis are associated with higher rates of malignant transformation towards cancer. We recently reported that aberrant activation of the Wnt/β‑catenin pathway is due to overexpression of Wnt ligands in oral dysplasia. However, the expression of other regulators of this pathway, namely components of the β-catenin destruction complex has not been explored in oral dysplasia.
Using immunohistochemical analyses, we evaluated nuclear expression of β‑catenin and its association with Wnt3a and Wnt5a. Likewise, components of the β-catenin destruction complex, including Adenomatous Polyposis Coli (APC), Axin and Glycogen Synthase Kinase 3 beta (GSK-3β) were also evaluated in oral dysplasia and OSCC biopsies.
We found that moderate and severe dysplasia samples, which harbored increased expression of nuclear β‑catenin, depicted augmented cytoplasmic expression of GSK‑3β, Axin and APC, in comparison with OSCC samples. Also, GSK-3β was found nuclear in mild dysplasia and OSCC samples, when compared with other study samples.
Cytoplasmic levels of components of the β-catenin destruction complex are increased in oral dysplasia and might be responsible of augmented nuclear β‑catenin.
口腔癌是世界上第六种最常见的癌症，其 5 年生存率为 40-50%。在口腔恶性肿瘤中，口腔鳞状细胞癌（OSCC）常伴有潜在的恶性病变，根据组织病理学标准，这些病变被称为口腔上皮内瘤变，其诊断与恶性转化为癌症的几率较高相关。我们最近报道，Wnt/β-catenin 通路的异常激活是由于口腔上皮内瘤变中 Wnt 配体的过度表达所致。然而，该通路的其他调节因子的表达，即β-catenin 降解复合物的成分，在口腔上皮内瘤变中尚未得到探索。
我们使用免疫组织化学分析评估了核β-catenin 的表达及其与 Wnt3a 和 Wnt5a 的相关性。同样，我们还评估了β-catenin 降解复合物的成分，包括腺瘤性结肠息肉病（APC）、轴蛋白和糖原合成酶激酶 3β（GSK-3β）在口腔上皮内瘤变和 OSCC 活检中的表达。
我们发现，中重度上皮内瘤变样本中，核β-catenin 表达增加，与 OSCC 样本相比，GSK-3β、轴蛋白和 APC 的细胞质表达增加。此外，与其他研究样本相比，轻度上皮内瘤变和 OSCC 样本中 GSK-3β 为核表达。
口腔上皮内瘤变中β-catenin 降解复合物的细胞质水平增加，可能导致核β-catenin 的增加。
