Lack of claudin-7 is a strong predictor of regional recurrence in oral and oropharyngeal squamous cell carcinoma
Lack of claudin-7 is a strong predictor of regional recurrence in oral and oropharyngeal squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2013.07.008
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发表时间：
2013-10-01
期刊：
影响因子：
4.8
通讯作者：
Schuuring, E.
中科院分区：
文献类型：
--
作者：
Melchers, L. J.;de Bruin, L. Bruine;Schuuring, E.
目的：口腔和口咽鳞状细胞癌（OSCC）的充分治疗取决于正确预测淋巴结转移的存在。目前诊断淋巴结转移的方法部分导致过度治疗与相关的发病率和治疗不足与无病生存率下降。钙粘蛋白作为淋巴结转移的潜在标志物已被广泛研究。EpCAM和claudin-7与E-钙粘蛋白具有功能关系，形成促进体外致瘤性的复合物。我们假设这些相关分子的共表达模式是一个更好的预后指标，为nodal status和regional recurrency.Materials和Methods：我们构建了单独的组织芯片的肿瘤中心和肿瘤浸润前沿的227口腔鳞癌完整的临床病理和随访数据，包括HPV状态，并进行免疫组化这些分子。缺乏E-钙粘蛋白和存在的细胞质EpCAM表达的肿瘤前沿预测淋巴结转移，但没有发现临床相关的共表达模式。在肿瘤中心缺乏claudin-7高度独立地预测较短的区域无病生存期（HR = 0.19; 95%CI：0.06-0.62）和疾病特异性生存期（HR = 0.43; 95%CI：0.21-0.87）。高危型HPV与任何marker.Conclusions：E-cadherin和EpCAM的表达，取决于特定的肿瘤亚定位，是预测淋巴结状态。然而，共表达并没有改善对淋巴结状态的预测，表明所提出的体外复合物在临床样品中没有功能。此外，在肿瘤中心缺乏claudin-7表达可用于识别区域复发风险增加的患者。(C)2013爱思唯尔有限公司保留所有权利。
Objectives: Adequate treatment of oral and oropharyngeal squamous cell carcinoma (OSCC) is dependent on correctly predicting the presence of lymph node metastases. Current methods to diagnose nodal metastases partly result in overtreatment with associated morbidity and undertreatment with decreased disease-free survival. E-cadherin has been studied extensively as potential marker for lymph node metastases. EpCAM and claudin-7 have a functional relationship with E-cadherin, forming a complex that promotes tumourigenicity in vitro. We hypothesize that the co-expression patterns of these related molecules is a better prognostic marker for nodal status and regional recurrences.Materials and methods: We constructed separate tissue microarrays of tumour centre and tumour invasive front of 227 OSCC with complete clinicopathological and follow-up data, including HPV status, and performed immunohistochemistry for these molecules.Results: Lack of E-cadherin and presence of cytoplasmic EpCAM expression in the tumour front were predictive for nodal metastasis, but no co-expression pattern was found clinically relevant. Lack of claudin-7 in the tumour centre was highly and independently predictive for shorter regional disease-free survival (HR = 0.19; 95% CI: 0.06-0.62) and disease-specific survival (HR = 0.43; 95% CI: 0.21-0.87). High-risk HPV was not associated with any marker.Conclusions: The expression of E-cadherin and EpCAM, depending on the specific tumour sublocalization, is predictive for nodal status. However, co-expression did not improve the prediction of nodal status, indicating that the proposed in vitro complex is not functional in clinical samples. Additionally, lack of claudin-7 expression in the tumour centre may be used to identify patients with increased risk for regional recurrence. (C) 2013 Elsevier Ltd. All rights reserved.