Thankappan Prasanth, Ramadoss Madhavan Nirmal, Joseph Tharmasahayam Isaac, Augustine Percy Ida, Shaga Isaacjoseph Bevin, Thilak Jashree
Department of Oral and Maxillofacial Pathology, Sree Mookambika Institute of Dental Sciences, Kulasekharam, Kanyakumari District, Tamil Nadu, India.
Department of Oral and Maxillofacial Pathology, Rajah Muthiah Dental College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India.
Rambam Maimonides Med J. 2021 Oct 25;12(4):e0028. doi: 10.5041/RMMJ.10451.
To study the correlation between the putative cancer stem cell (CSC) markers aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 44 (CD44), sex-determining region Y-box 2 (SOX2), and octamer-binding protein 4 (OCT4) and human papilloma virus (HPV) infection using p16, the surrogate marker of HPV in oral epithelial dysplasia (OED) and normal mucosa.
Five sections each from 40 histopathologically diagnosed cases of different grades of OED and 10 cases of normal oral mucosa without dysplasia were immunohistochemically stained with p16, ALDH1, CD44, SOX2, and OCT4, respectively.
Expression of ALDH1 and SOX2 was significantly increased in OED cases, whereas CD44 and OCT4 expression was increased in normal mucosa. P16-positive OED cases showed upregulation of ALDH1 and OCT4 expression as compared to p16-negative cases, while CD44 and SOX2 expression was downregulated in p16-positive OED cases; however, the results were not statistically significant.
The present study indicated a suggestive link between p16 and cancer stem cell marker expression in HPV-associated OED, and that p16 has a significant role in CSC progression in OED. This is the first study to evaluate the expression of putative CSC markers in HPV-associated OED. However, low study numbers are a potential limiting factor in this study.
使用p16(口腔上皮发育异常(OED)和正常黏膜中HPV的替代标志物)研究假定的癌症干细胞(CSC)标志物醛脱氢酶1(ALDH1)、分化簇44(CD44)、性别决定区Y框2(SOX2)和八聚体结合蛋白4(OCT4)与人类乳头瘤病毒(HPV)感染之间的相关性。
分别对40例经组织病理学诊断的不同等级OED病例和10例无发育异常的正常口腔黏膜病例各取5个切片,进行p16、ALDH1、CD44、SOX2和OCT4的免疫组织化学染色。
OED病例中ALDH1和SOX2的表达显著增加,而正常黏膜中CD44和OCT4的表达增加。与p16阴性病例相比,p16阳性的OED病例中ALDH1和OCT4的表达上调,而p16阳性的OED病例中CD44和SOX2的表达下调;然而,结果无统计学意义。
本研究表明在HPV相关的OED中p16与癌症干细胞标志物表达之间存在提示性联系,且p16在OED的CSC进展中起重要作用。这是第一项评估HPV相关OED中假定的CSC标志物表达的研究。然而,样本量少是本研究的一个潜在限制因素。