Zisis Vasileios, Paraskeuopoulos Konstantinos, Athanasios Poulopoulos, Panta Prashanth, Dimitrios Andreadis
Oral Medicine/ Pathology, Aristotle University of Thessaloniki, Thessaloniki, GRC.
Oral & Maxillofacial Surgery, Aristotle University of Thessaloniki, Thessaloniki, GRC.
Cureus. 2023 Jun 22;15(6):e40836. doi: 10.7759/cureus.40836. eCollection 2023 Jun.
Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis by enabling the self-renewal and self-proliferation of the cancer cells. This study aimed to investigate the presence of epithelial cells with cancer stem cells characteristics (ALDH+) in the early stages of oral precancerous lesions (Oral Leukoplakias) and the frequency of these cells in the different stages of oral squamous cell carcinomas (OSCCs).
MATERIALS & METHODS: The aim of this study was the detection of the immunohistochemical pattern of expression of CSC protein-biomarker ALDH1&2 (sc-166362, Santa Cruz Co, Dallas, Texas, USA) in paraffin-embedded samples of 30 cases of leukoplakia of all degrees of dysplasia and 21 cases of oral squamous cell carcinomas (OSCC) of all degrees of differentiation compared to the histologically normal oral epithelium. The samples were retrieved from 2009-2019 from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece. The samples were evaluated through a three-tier scale (positive cells Ι: 6-35%, ΙΙ: 36-70%, ΙΙΙ: 71-100%). Statistical analysis was performed through SPSS Pearson Chi-square, and the significance level was set at 0.05 (p=0.05). Results: The staining of ALDH1&2 was observed mildly in the cell membrane of cells in the stratum spinosum of the normal epithelium and the cell membrane of cells in the stratum basale of the normal epithelium, characteristically at the interface point with the basal membrane. ALDH1&2 were expressed significantly more in the OSCC than in the leukoplakia (p-value=0.0001) and the normal epithelium (p-value=0.0001). Mainly, ALDH1&2 were expressed significantly more in the severely and moderately dysplastic oral leukoplakia compared to the mildly dysplastic and non-dysplastic leukoplakia (p-value=0.001).
The characteristic expression of ALDH in potentially malignant oral and OSCC lesions suggests the presence of CSCs and their possible implication in the early stages of oral tumorigenesis, even at the stage of oral leukoplakia.
癌症干细胞(CSCs)通过使癌细胞自我更新和自我增殖,引发致癌过程。本研究旨在调查口腔癌前病变(口腔白斑)早期具有癌症干细胞特征的上皮细胞(ALDH+)的存在情况,以及这些细胞在口腔鳞状细胞癌(OSCC)不同阶段的频率。
本研究的目的是检测癌症干细胞蛋白生物标志物ALDH1&2(sc-166362,美国德克萨斯州达拉斯市圣克鲁斯公司)在30例不同程度发育异常的白斑石蜡包埋样本和21例不同分化程度的口腔鳞状细胞癌(OSCC)中的免疫组化表达模式,并与组织学正常的口腔上皮进行比较。样本于2009年至2019年从希腊塞萨洛尼基亚里士多德大学牙科学院口腔医学/病理学系档案中获取。样本通过三级评分标准进行评估(阳性细胞Ⅰ:6 - 35%,Ⅱ:36 - 70%,Ⅲ:71 - 100%)。通过SPSS Pearson卡方检验进行统计分析,显著性水平设定为0.05(p = 0.05)。结果:在正常上皮棘层细胞的细胞膜和正常上皮基底层细胞的细胞膜中,观察到ALDH1&2呈轻度染色,特征性地出现在与基底膜的交界点。ALDH1&2在OSCC中的表达明显高于白斑(p值 = 0.0001)和正常上皮(p值 = 0.0001)。主要地,与轻度发育异常和无发育异常的白斑相比,ALDH1&2在重度和中度发育异常的口腔白斑中的表达明显更高(p值 = 0.001)。
ALDH在潜在恶性的口腔和OSCC病变中的特征性表达表明癌症干细胞的存在及其在口腔肿瘤发生早期阶段(甚至在口腔白斑阶段)可能的作用。