Attramadal Cecilie Gjøvaag, Kumar Sheeba, Boysen Morten E, Dhakal Hari Prasad, Nesland Jahn Marthin, Bryne Magne
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Anticancer Res. 2015 Nov;35(11):6111-20.
BACKGROUND: Early oral carcinomas have a high recurrence rate despite surgery with clear margins. In an attempt to classify the risk of recurrence of oral squamous cell carcinomas, we explored the significance of tumor budding, epithelial-mesenchymal transition (EMT) and certain cancer stem cell markers (CSC). MATERIALS AND METHODS: Tumor budding (single cells or clusters of ≤5 cells in the tumor front, divided into high- and low-budding tumors), EMT and CSC markers were studied in 62 immunohistochemically stained slides of T1/2N0M0 oral squamous cell carcinomas. Tissues and records of follow-up were obtained from the Oslo University Hospital, Norway. Tumor budding, EMT and CSC markers were scored and analyzed. RESULTS: The only significant prognostic marker was tumor budding (p=0.043). Expression of the EMT marker E-cadherin was lost from the invasive front and tended to be a prognostic factor (p=0.17), and up-regulation of vimentin in tumor cells in the invasive front was found; this indicates that EMT had occurred. CSC markers were not associated with recurrence rate in the present study. CONCLUSION: A high budding index was related to poor prognosis in patients with oral cancer. Budding was associated with EMT-like changes. CSC factors were detected but reflected differentiation rather than stemness. Scoring of buds in patients with oral cancer may help discriminate invasive tumors prone to relapse, and thus, provide an indication for adjuvant therapy.
背景:早期口腔癌即便手术切缘阴性,复发率仍很高。为了对口腔鳞状细胞癌的复发风险进行分类,我们探讨了肿瘤芽生、上皮-间质转化(EMT)及某些癌症干细胞标志物(CSC)的意义。 材料与方法:在62张T1/2N0M0口腔鳞状细胞癌免疫组织化学染色切片中研究肿瘤芽生(肿瘤前沿单个细胞或≤5个细胞的细胞簇,分为高芽生肿瘤和低芽生肿瘤)、EMT及CSC标志物。组织和随访记录来自挪威奥斯陆大学医院。对肿瘤芽生、EMT及CSC标志物进行评分和分析。 结果:唯一显著的预后标志物是肿瘤芽生(p=0.043)。EMT标志物E-钙黏蛋白在浸润前沿表达缺失,且有成为预后因素的趋势(p=0.17),同时发现浸润前沿肿瘤细胞中波形蛋白上调;这表明发生了EMT。在本研究中,CSC标志物与复发率无关。 结论:高芽生指数与口腔癌患者预后不良相关。芽生与类似EMT的改变有关。检测到了CSC因子,但它们反映的是分化而非干性。对口腔癌患者的芽生进行评分可能有助于鉴别易复发的浸润性肿瘤,从而为辅助治疗提供依据。
Anticancer Res. 2015-11
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