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醛脱氢酶1作为口腔鳞状细胞癌淋巴结转移的预后标志物。

ALDH1 as a prognostic marker for lymph node metastasis in OSCC.

作者信息

Götz Carolin, Bissinger Oliver, Nobis Christopher, Wolff Klaus Dietrich, Drecoll Enken, Kolk Andreas

机构信息

Department of Oral and Maxillofacial Surgery, Technical University of Munich, D-81675 Munich, Germany.

Institute of Pathology, Klinikum Rechts der Isar, Technical University of Munich, D-81675 Munich, Germany.

出版信息

Biomed Rep. 2018 Oct;9(4):284-290. doi: 10.3892/br.2018.1131. Epub 2018 Jul 17.

Abstract

Long-term survival in cases of head and neck squamous cell carcinoma, particularly oral squamous cell carcinoma (OSCC), remains a rare achievement in the field of clinical oncology. In recent years, the theory of cancer stem cells (CSCs) has emerged and been used to offer explanations for tumour recurrence and metastasis. The present aim was to investigate the role of aldehyde dehydrogenase 1 (ALDH1) as a CSC-marker for OSCC and to determine the role of p16, which is also a surrogate marker of human papilloma virus (HPV), in the expression of ALDH1. The study cohort comprised of 186 surgically-treated cases of OSCC. The primaries were located in the oral cavity. The expression of the CSC marker (CSCM) ALDH1 was evaluated via immunohistochemistry (IHC) of a tissue microarray. HPV detection was performed by polymerase chain reaction and an HPV Array kit. Furthermore, the IHC expression of p16 was also analysed. Risk regression models as the Kruskal Wallis test was used to assess the association of CSCM and p16 expression with tumour size and lymph node metastasis, and cox proportional hazards were analysed. Additionally, coexpression of the markers ALDH1 and p16 was analysed with regard to associations with tumour classification. Overall, high expression of ALDH1 in lymph nodes was significantly associated with Union for International Cancer Control (UICC) stage IV (P=0.044) and T4 stage cancer (P=0.03). p16 positivity, in cases of HPV negativity, was associated with worse survival rate compared with that of the total cohort (P=0.048). Collectively the data indicate that ALDH1 expression may be suitable for detection of unfavourable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. HPV status was not statistically predictive of patient outcome or CSCM expression; however, p16 remains a potential marker in HNSCC Further studies with ALDH1 and p16 should be performed to evaluate the expression of ALDH1 and HPV in cell culture and to clarify the role of ALDH1 as a marker for increased invasiveness of OSCC cells.

摘要

在头颈鳞状细胞癌,尤其是口腔鳞状细胞癌(OSCC)病例中,长期生存仍是临床肿瘤学领域一项罕见的成果。近年来,癌症干细胞(CSC)理论已出现,并被用于解释肿瘤复发和转移。目前的目的是研究醛脱氢酶1(ALDH1)作为OSCC的CSC标志物的作用,并确定同样作为人乳头瘤病毒(HPV)替代标志物的p16在ALDH1表达中的作用。研究队列包括186例接受手术治疗的OSCC病例。原发灶位于口腔。通过组织微阵列的免疫组织化学(IHC)评估CSC标志物(CSCM)ALDH1的表达。通过聚合酶链反应和HPV Array试剂盒进行HPV检测。此外,还分析了p16的IHC表达。使用Kruskal Wallis检验等风险回归模型来评估CSCM和p16表达与肿瘤大小和淋巴结转移的相关性,并分析Cox比例风险。此外,分析了标志物ALDH1和p16的共表达与肿瘤分类的相关性。总体而言,淋巴结中ALDH1的高表达与国际癌症控制联盟(UICC)IV期(P=0.044)和T4期癌症(P=0.03)显著相关。在HPV阴性的病例中,p16阳性与整个队列相比生存率较差相关(P=0.048)。总体而言,数据表明ALDH1表达可能适用于检测OSCC患者的不良预后,部分基于其作为转移标志物的明显作用。HPV状态对患者预后或CSCM表达没有统计学预测价值;然而,p16仍然是头颈部鳞状细胞癌的一个潜在标志物。应进一步开展关于ALDH1和p16的研究,以评估ALDH1和HPV在细胞培养中的表达,并阐明ALDH1作为OSCC细胞侵袭性增加标志物的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2ae/6142035/da590a60d689/br-09-04-0284-g00.jpg

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