de Freitas Filho Silas Antonio Juvencio, Coutinho-Camillo Cláudia Malheiros, Oliveira Katia Klug, Bettim Bárbara Beltrame, Pinto Clóvis Antônio Lopes, Kowalski Luiz Paulo, Oliveira Denise Tostes
Department of Surgery, Stomatology, Pathology and Radiology (Area of Pathology), Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil.
J Oncol. 2021 Feb 13;2021:6663720. doi: 10.1155/2021/6663720. eCollection 2021.
The present study aimed to investigate the clinical significance and prognostic value of the immunoexpression of cancer stem cell markers, ALDH1 and Notch1, in subtypes of oral squamous cell carcinoma.
The expression of ALDH1 and Notch1 in 63 patients with well and poorly differentiated oral squamous cell carcinomas and their subtypes, verrucous carcinoma and basaloid squamous cell carcinoma, was evaluated by immunohistochemistry. The semi-quantitative analysis of the ALDH1 and Notch immunoexpression levels, based on the capture of 10 microscopic fields, at 400X magnification, at the invasive tumor front was performed and associated with clinicopathological variables using the chi-square test or Fisher's exact test. The overall and disease-free survival rates were estimated according to the Kaplan-Meier method and the curves were compared using the log-rank test. The independent effects of variables were calculated using Cox's proportional hazards regression model.
Strong ALDH1 and Notch1 expression was observed in 16 (25.4%) and 27 (42.9%) oral squamous cell carcinomas including their subtypes, respectively. Most tumors with strong immunoexpression of ALDH1 were basaloid squamous cell carcinoma (56.3%). Statistically significant associations were observed between the strong immunoexpression of Notch1 in poorly differentiated oral squamous cell carcinoma with perineural infiltration ( = 0.011) and lymph node involvement (pN+) ( = 0.034). The strong immunoexpression of ALDH1 was a prognostic factor associated with worse overall survival ( = 0.040) for patients with oral cancer.
The strong immunoexpression of Notch1 can contribute to identification of patients with poorly differentiated oral squamous cell carcinoma, who have perineural infiltration or lymph node metastasis. In addition, the strong immunoexpression of ALDH1 may help to identify a worse prognosis in patients with oral squamous cell carcinoma and their subtypes.
本研究旨在探讨癌症干细胞标志物醛脱氢酶1（ALDH1）和Notch1的免疫表达在口腔鳞状细胞癌各亚型中的临床意义及预后价值。
采用免疫组织化学方法评估63例高分化和低分化口腔鳞状细胞癌及其亚型（疣状癌和基底样鳞状细胞癌）患者中ALDH1和Notch1的表达。在400倍放大倍数下，于肿瘤浸润前沿捕获10个显微镜视野，对ALDH1和Notch免疫表达水平进行半定量分析，并使用卡方检验或Fisher精确检验将其与临床病理变量相关联。根据Kaplan-Meier方法估计总生存率和无病生存率，并使用对数秩检验比较曲线。使用Cox比例风险回归模型计算变量的独立效应。
在包括各亚型在内的16例（25.4%）和27例（42.9%）口腔鳞状细胞癌中分别观察到ALDH1和Notch1的强表达。大多数ALDH1强免疫表达的肿瘤为基底样鳞状细胞癌（56.3%）。在低分化口腔鳞状细胞癌中，Notch1的强免疫表达与神经周浸润（P = 0.011）和淋巴结受累（pN+）（P = 0.034）之间存在统计学显著关联。ALDH1的强免疫表达是口腔癌患者总生存率较差相关的预后因素（P = 0.040）。
Notch1的强免疫表达有助于识别伴有神经周浸润或淋巴结转移的低分化口腔鳞状细胞癌患者。此外，ALDH1的强免疫表达可能有助于识别口腔鳞状细胞癌及其亚型患者的较差预后。
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