INSERM U728, RayLab, and Departments of Medical Oncology, Beaujon University Hospital (AP-HP - Paris 7 Diderot), Clichy, France.
Oral Oncol. 2012 Dec;48(12):1263-71. doi: 10.1016/j.oraloncology.2012.06.010. Epub 2012 Jul 7.
The aim of this study was to evaluate the expression and the prognostic value of chemokine receptor 4 (CXCR4), its cognate ligand the CXCL12, and markers of epithelial-to-mesenchymal transition (EMT) in squamous cell carcinoma (SCC) of the mobile tongue.
Patients with primary SCC of the mobile tongue who underwent surgery in our center were screened retrospectively. Patients without prior treatment, who had pre-surgery TNM staging and available tumor samples, were eligible. Protein expression of CXCL12, CXCR4, CA9, E-cadherin, and vimentin was determined by immunohistochemical staining, scored, and correlated with clinical and pathological parameters and overall survival. Multivariate and Cox proportional hazards analyses were performed.
Among 160 patients treated and screened, 47 were analyzed. CXCR4 and CXCL12 expression was high in tumor cells. CXCR4 expression in primary tumor samples was significantly higher in patients with high-grade tumors, lymph node metastases, and microscopic nerve invasion (p ≤ 0.05). There was a non-significant trend towards a correlation between high CXCL12 expression and pathologic tumor stage (p=0.07). Tumors with high CXCR4 expression correlated with poor overall survival (hazard ratio=3.6, 95% confidence interval 1.3-9.7; p=0.011), notably in the CXCR4(high)/vimentin-positive subgroup. Vimentin-positive tumors, characterizing EMT, were associated with lower survival (hazard ratio=4.5, 95% confidence interval 1.6-12.3; p=0.0086). Multivariate analysis confirmed vimentin (but not CXCR4) expression as an independent prognostic factor of poor overall survival (p=0.016).
Our results suggest that CXCR4 is a marker of tumor aggressiveness and vimentin is an important and independent prognostic factor in patients with SCC of the mobile tongue.
本研究旨在评估趋化因子受体 4（CXCR4）及其配体趋化因子 12（CXCL12）以及上皮间质转化（EMT）标志物在舌移动部鳞状细胞癌（SCC）中的表达及其预后价值。
我们对在中心接受手术的原发性舌移动部 SCC 患者进行了回顾性筛选。符合以下条件的患者可入选：未经前期治疗、术前 TNM 分期明确且有肿瘤样本可用。采用免疫组化染色法测定 CXCL12、CXCR4、CA9、E-钙黏蛋白和波形蛋白的蛋白表达情况，进行评分，并与临床病理参数和总生存相关联。进行了多变量和 Cox 比例风险分析。
在 160 例经治疗和筛选的患者中，有 47 例进行了分析。肿瘤细胞中 CXCR4 和 CXCL12 的表达较高。在高级别肿瘤、淋巴结转移和显微镜下神经侵犯的患者中，原发肿瘤标本中 CXCR4 的表达明显更高（p≤0.05）。CXCL12 高表达与病理肿瘤分期呈非显著相关趋势（p=0.07）。CXCR4 高表达的肿瘤与总生存不良相关（风险比=3.6，95%置信区间 1.3-9.7；p=0.011），尤其是在 CXCR4（高）/波形蛋白阳性亚组中。EMT 特征的波形蛋白阳性肿瘤与生存率降低相关（风险比=4.5，95%置信区间 1.6-12.3；p=0.0086）。多变量分析证实，波形蛋白（而非 CXCR4）表达是总生存不良的独立预后因素（p=0.016）。
我们的研究结果表明，CXCR4 是肿瘤侵袭性的标志物，而波形蛋白是舌移动部 SCC 患者重要的独立预后因素。
