Ghazi Narges, Saghravanian Nasrollah, Taghi Shakeri Mohammad, Jamali Mounes
Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran.
Dept. of Community Medicine and Public Health, Mashhad University of Medical Sciences, Mashhad, Iran.
J Dent (Shiraz). 2021 Mar;22(1):33-40. doi: 10.30476/DENTJODS.2020.84393.1079.
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Early diagnosis of OSCC by using biomarkers provides preventive treatment approach to suppress the disease in early stages. CD44 as a cancer stem cell (CSC) marker may be cleaved by MT1-MMP and plays an important role in migration of cancer cells. TGF-B promotes formation of invasive cancer cells phenotype through epithelial mesenchymal transition (EMT) and induces MT1-MMP formation.
The aim of this study was to evaluate the expression of TGF-B and CD44 in leukoplakia (premalignant lesion), squamous cell carcinoma (SCC), and normal oral mucosa to determine the role of these markers in the carcinogenesis process of the oral mucosa.
In this retrospective study, the expression of TGF-B and CD44 were evaluated in 55 paraffin-embedded specimens (10normal mucosa, 15 non-dysplastic leukoplakia, 15 dysplastic leukoplakia, and 15 OSCC) by immunohistochemistry. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney, and Spearman's rank correlation tests.
Evaluation of CD44 and TGF-B expression in the four studied groups showed statistical significant difference for each marker (< 0.001). Pairwise comparison of CD44 and TGF-B expression in all groups except normal mucosa and non-dysplastic leukoplakia demonstrated statistical significant difference. In addition, there was positive significant correlation between two markers (r= 0.914, < 0.001). Diagnostic test's accuracy for identification of OSCC and dysplastic leukoplakia from non-dysplastic leukoplakia and normal tissues and recognition of OSCC from dysplastic leukoplakia showed optimum sensitivity and specificity.
Increased expression of CD44 as a cancer stem cell marker and TGF-B as an EMT marker from normal mucosa to non-dysplastic leukoplakia, dysplastic leukoplakia, and OSCC and also the significant correlation between these two markers indicated their role in carcinogenesis of oral mucosa.
口腔鳞状细胞癌(OSCC)是口腔最常见的恶性肿瘤。通过使用生物标志物对OSCC进行早期诊断可提供预防性治疗方法,以在疾病早期抑制该疾病。CD44作为一种癌症干细胞(CSC)标志物,可能被MT1-MMP裂解,并在癌细胞迁移中起重要作用。转化生长因子-β(TGF-β)通过上皮-间质转化(EMT)促进侵袭性癌细胞表型的形成,并诱导MT1-MMP的形成。
本研究旨在评估TGF-β和CD44在白斑(癌前病变)、鳞状细胞癌(SCC)和正常口腔黏膜中的表达,以确定这些标志物在口腔黏膜癌变过程中的作用。
在这项回顾性研究中,通过免疫组织化学评估了55个石蜡包埋标本(10例正常黏膜、15例非发育异常白斑、15例发育异常白斑和15例OSCC)中TGF-β和CD44的表达。使用Kruskal-Wallis检验、Mann-Whitney检验和Spearman等级相关检验进行统计分析。
对四个研究组中CD44和TGF-β表达的评估显示,每个标志物均有统计学显著差异(<0.001)。除正常黏膜和非发育异常白斑外,所有组中CD44和TGF-β表达的两两比较均显示有统计学显著差异。此外,两种标志物之间存在显著正相关(r = 0.914,<0.001)。从非发育异常白斑和正常组织中识别OSCC和发育异常白斑以及从发育异常白斑中识别OSCC的诊断试验准确性显示出最佳的敏感性和特异性。
从正常黏膜到非发育异常白斑、发育异常白斑和OSCC,作为癌症干细胞标志物的CD44和作为EMT标志物的TGF-β表达增加,并且这两种标志物之间的显著相关性表明它们在口腔黏膜癌变中的作用。