Nader Marina, Soliman Samar, Yussif Shaimaa M, El-Sissi Azza Abbas
Faculty of Dentistry, Mansoura University, Mansoura, Egypt.
Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Diagn Pathol. 2025 Apr 11;20(1):41. doi: 10.1186/s13000-025-01627-0.
Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral malignancies. The poorly understood molecular and cellular mechanisms underlying the pathogenesis of OSCC remain a subject of paramount importance. For epithelial dysplasia, invasion, and metastasis to occur, tumor cells require energy obtained from the mitochondria and phenotypic cellular changes in the actin cytoskeleton. Dynamin-related protein1 (Drp1) is one of the main mitochondrial proteins regulating the mitochondrial dynamics. Cortactin is an actin-binding protein that promotes the actin polymerization and rearrangement. The interplay between both proteins in OSCC remains elusive. The current study aimed to investigate the immunohistochemical (IHC) expression of Drp1 and cortactin in tissues revealing propagating OSCC cases.
The retrospective study was carried out on 35 formalin-fixed paraffin sections of nodal metastasizing OSCC cases selected from the Oncology Centre, Faculty of Medicine, Mansoura University archives from 2018 to 2023. Immunohistochemistry for Drp1 and cortactin was done. The immune reactivity of both proteins was evaluated using computer-assisted digital image analysis. Statistical analysis was performed to identify significant differences and correlations between both markers in tissues associated with progressing OSCC cases using Chi-Square, Monte Carlo, One-Way ANOVA, and Spearman tests. The p-value less than 0.05 was considered statistically significant.
Drp1 expression was statistically significant to grades of primary OSCC (p = 0.015), while insignificant to grades of epithelial dysplasia (p = 0.123) and metastatic lymph nodes (LNs) (p = 0.212). Statistically significant differences between dysplastic epithelium & primary tumor, dysplastic epithelium & metastatic LNs, and primary tumor and metastatic LNs were observed (p values were 0.014, 0.001, 0.034, respectively). On the other hand, Cortactin expression revealed no statistically significant differences across the three groups. However, statistically significant differences between dysplastic epithelium & primary tumor, dysplastic epithelium & metastatic LNs, and primary tumor and metastatic LNs were found (p values were 0.014, 0.001, 0.034, respectively). Moreover, the Spearman test presented a strong positive correlation between Drp1 and cortactin expression in the studied cases.
Expressions of both Drp1 and cortactin relatively explain their great role in the propagation and the carcinogenesis of OSCC.
口腔鳞状细胞癌（OSCC）占口腔恶性肿瘤的90%以上。OSCC发病机制中尚未完全了解的分子和细胞机制仍然是至关重要的研究课题。为了发生上皮发育异常、侵袭和转移，肿瘤细胞需要从线粒体获得能量以及肌动蛋白细胞骨架的细胞表型变化。动力蛋白相关蛋白1（Drp1）是调节线粒体动力学的主要线粒体蛋白之一。皮层肌动蛋白是一种肌动蛋白结合蛋白，可促进肌动蛋白的聚合和重排。这两种蛋白在OSCC中的相互作用仍不清楚。本研究旨在调查Drp1和皮层肌动蛋白在显示进展期OSCC病例的组织中的免疫组化（IHC）表达。
对2018年至2023年从曼苏拉大学医学院肿瘤中心档案中选取的35例发生淋巴结转移的OSCC病例的福尔马林固定石蜡切片进行回顾性研究。对Drp1和皮层肌动蛋白进行免疫组化。使用计算机辅助数字图像分析评估这两种蛋白的免疫反应性。进行统计分析，以确定使用卡方检验、蒙特卡罗检验、单因素方差分析和Spearman检验在与进展期OSCC病例相关的组织中这两种标志物之间的显著差异和相关性。p值小于0.05被认为具有统计学意义。
Drp1表达与原发性OSCC的分级具有统计学意义（p = 0.015），而与上皮发育异常分级（p = 0.123）和转移性淋巴结（LNs）（p = 0.212）无关。观察到发育异常上皮与原发性肿瘤、发育异常上皮与转移性LNs以及原发性肿瘤与转移性LNs之间存在统计学显著差异（p值分别为0.014、0.001、0.034）。另一方面，皮层肌动蛋白表达在三组之间未显示出统计学显著差异。然而，发现发育异常上皮与原发性肿瘤、发育异常上皮与转移性LNs以及原发性肿瘤与转移性LNs之间存在统计学显著差异（p值分别为0.014、0.001、0.034）。此外，Spearman检验显示在研究病例中Drp1和皮层肌动蛋白表达之间存在强正相关。
Drp1和皮层肌动蛋白的表达相对解释了它们在OSCC的传播和致癌作用中的重要作用。
