Bacchiocchi Roberta, Rubini Corrado, Pierpaoli Elisa, Borghetti Giulia, Procacci Pasquale, Nocini Pier Francesco, Santarelli Andrea, Rocchetti Romina, Ciavarella Domenico, Lo Muzio Lorenzo, Fazioli Francesca
Department of Molecular Pathology and Innovative Therapies, Polytechnic University of the Marche Region, Ancona, Italy.
BMC Cancer. 2008 Aug 1;8:220. doi: 10.1186/1471-2407-8-220.
Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia.
In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate.
In our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives.
The results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients.
口腔鳞状细胞癌（OSCC）是最常见的口腔恶性肿瘤。尽管近年来治疗方法有所进展，但仍有高达50%的病例会复发和/或转移。因此，迫切需要鉴定能够预测这些病变临床行为的新生物标志物，以提高生活质量和总体生存率。在已知参与其他肿瘤形成的肿瘤进展生物标志物中，尿激酶型纤溶酶原激活物受体（uPAR）起着关键作用，它不仅作为酶原pro-uPA的受体，而且作为细胞黏附成分和趋化因子，在细胞外蛋白水解、细胞迁移和组织重塑中发挥多种作用。本研究的目的是获取有关uPAR在OSCC中表达的信息，并验证该分子是否可作为这种肿瘤的预后/预测标志物。
在一项回顾性研究中，通过免疫组织化学对189例OSCC患者队列进行uPAR表达及其细胞定位的研究。作为标准对照，对8例无口腔肿瘤证据或病史的患者的正常口腔黏膜组织进行同样的研究。根据uPAR表达分组后，对OSCC患者的年龄、性别、组织学分级（G）、肿瘤大小、复发情况、TNM分期和总生存率等变量进行统计学分析。
在我们的免疫组织化学研究中，74例（39.1%）OSCC显示uPAR主要呈细胞质阳性，而115例为阴性。uPAR表达与肿瘤分化程度和预后相关：G3组阳性病例百分比最高（70.4%），uPAR表达阳性的患者预期寿命低于uPAR阴性患者。
本研究结果表明uPAR作为一种潜在生物标志物，有助于识别OSCC患者中高风险亚组。
