Searching for new early detection markers of oral epithelial dysplasia and oral squamous cell carcinoma using oral liquid-based cytology

IF 0.4 Q4 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Oral and Maxillofacial Surgery Medicine and Pathology Pub Date : 2023-11-25 DOI:10.1016/j.ajoms.2023.11.007

Toshiyuki Akimori , Manabu Yamazaki , Tatsuya Abé , Satoshi Maruyama , Kei Tomihara , Takeyasu Maeda , Jun-ichi Tanuma

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Abstract

Objective

Oral squamous cell carcinomas (SCCs) arise from oral potentially malignant disorders (OPMDs), including oral epithelial dysplasia (OED); however, useful detections markers for early detection of OED and oral SCC are lacking. In this study, we aimed to evaluate the sequential mRNA and protein expression patterns of BRD4, c-MYC, TP53, and MUC21 in human oral samples by liquid-based cytology (LBC) and determine whether these markers are useful for early detection of OED and oral SCC when combined with oral cytological screening.

Methods

A total 200 patients were obtained from our hospital between 2020 and 2022. These are samples from same cases with oral cytology and corresponding histological diagnosis. The expression of these markers was examined by immunocytochemistry and mRNA analysis. The percentages of cells with nuclear or cytoplasmic immunostaining were calculated using the labeling index (LI). BRD4, c-MYC, and TP53 mRNA expression levels were upregulated in tissue during progression from a status of negative for intraepithelial lesions or malignancy (NILM) to positive for SCC. BRD4-LI and c-MYC-LI significantly increased in low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) and SCC samples, whereas the expression of MUC21 mRNA and MUC21-LI gradually decreased. TP53-LI increased only in SCC samples.

Conclusions

We conclude that monitoring BRD4 and c-MYC expression with immunocytochemistry could improve the early detection of OED and oral SCC.

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利用口腔液基细胞学寻找新的 OED 和口腔 SCC 早期检测标记物

目的口腔鳞状细胞癌（SCC）源于口腔潜在恶性疾病（OPMD），包括口腔上皮发育不良（OED）；然而，目前还缺乏用于早期检测 OED 和口腔 SCC 的有用检测标记物。在本研究中，我们旨在通过液基细胞学（LBC）评估人类口腔样本中BRD4、c-MYC、TP53和MUC21的mRNA和蛋白表达模式，并确定这些标记物与口腔细胞学筛查相结合是否有助于早期检测OED和口腔SCC。这些样本来自口腔细胞学检查和相应组织学诊断的相同病例。通过免疫细胞化学和 mRNA 分析检测这些标记物的表达。使用标记指数（LI）计算细胞核或细胞质免疫染色的百分比。BRD4、c-MYC和TP53 mRNA的表达水平在组织从上皮内病变或恶性肿瘤阴性（NILM）到SCC阳性的过程中上调。在低级别鳞状上皮内病变（LSIL）、高级别鳞状上皮内病变（HSIL）和 SCC 样本中，BRD4-LI 和 c-MYC-LI 明显增加，而 MUC21 mRNA 和 MUC21-LI 的表达则逐渐减少。结论我们得出结论，用免疫细胞化学方法监测BRD4和c-MYC的表达可提高OED和口腔SCC的早期检测率。

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