Diagnostic and prognostic role of protein and ultrastructural alterations at cell–extracellular matrix junctions in neoplastic progression of human oral malignancy

Despite advancements in technology and increase in favorable outcomes associated with oral cancer, early detection remains the most significant factor in limiting mortality. The current study aimed to develop early diagnostic and prognostic markers for oral tumorigenesis. Protein and ultrastructural alterations at cell-extracellular matrix (ECM) adhesion junctions were examined concurrently using immunohistochemistry (IHC) and transmission electron microscopy (TEM) on progressive grade of oral carcinomas (n = 285). The expression of hemidesmosome (HD) proteins-integrin β4, BP180, and laminin-5 increased in hyperplasia as compared to normal, and significantly increased further, as the disease progressed. TEM analysis in parallel tissues revealed a significant decrease in HD number and increase in the length of basal lamina (BL) in hyperplasia. With cancer progression, the severity of ultrastructural alterations increased gradually and significantly. Overexpression of HD proteins, decrease in HD number and increase in BL length significantly correlated with nodal metastasis, local recurrence, and recurrence-free survival of patients. Concurrent use of IHC and TEM can add value to early recognition of neoplastic changes in primary carcinomas of oral cavity. In this regard, altered expression of integrin β4 and laminin-5, loss of HDs, and increased BL length could offer criteria for early diagnosis and prognosis of oral malignancy.

尽管当前技术已取得进步，口腔癌的相关获益也有所提升，但早期检测仍是限制该病死亡率的最核心因素。本研究旨在开发用于口腔肿瘤发生的早期诊断与预后标志物。研究采用免疫组织化学（IHC）与透射电子显微镜（TEM）联合方案，对285例不同进展分级的口腔癌样本中，细胞-细胞外基质（ECM）黏附连接处的蛋白质与超微结构改变进行同步分析。与正常组织相比，增生组织中半桥粒（HD）相关蛋白——整合素β4、BP180及层粘连蛋白-5的表达水平升高；且随着疾病进展，这些蛋白的表达进一步显著上调。配对组织的TEM分析显示，增生组织内的半桥粒数量显著减少，而基膜（BL）长度显著增加。随着癌症病程推进，超微结构改变的严重程度逐渐且显著加重。半桥粒蛋白过表达、半桥粒数量减少及基膜长度增加，均与患者的淋巴结转移、局部复发及无复发生存期显著相关。免疫组织化学与透射电子显微镜的联合应用，可为口腔原发性癌的肿瘤性改变早期识别提供辅助价值。在此背景下，整合素β4与层粘连蛋白-5的表达异常、半桥粒缺失及基膜长度增加，可作为口腔恶性肿瘤早期诊断与预后评估的参考指标。