De Schutter Harlinde, Landuyt Willy, Verbeken Erik, Goethals Laurence, Hermans Robert, Nuyts Sandra
Department of Radiation Oncology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
BMC Cancer. 2005 Apr 25;5:42. doi: 10.1186/1471-2407-5-42.
Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC) treated by radiotherapy +/- chemotherapy.
We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67), immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1 (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated.
For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005).
To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be the most important parameter to judge radiotherapy responses. Furthermore, the combined assessment of CA IX and GLUT-1 correlated independently with prognosis. This is a valuable indication that a combined approach is important in the investigation of prognostic markers.
肿瘤微环境的几个参数，如缺氧、炎症和血管生成，在肿瘤侵袭性和治疗反应中起关键作用。这些标志物是否可用于将患者分层至特定治疗方案仍是一个主要问题。本研究的目的是调查接受放疗±化疗的头颈部鳞状细胞癌（HNSCC）患者中几种生物学和临床病理参数的相互关系及预后意义。
我们使用了一个回顾性系列的两个亚组，其中CT测定的肿瘤灌注与局部控制相关。在第一个亚组（n = 67）中，对预处理的肿瘤活检组织进行碳酸酐酶IX（CA IX）和葡萄糖转运蛋白-1（GLUT-1）的免疫组织化学检测。在第二个亚组（n = 34）中，使用酶联免疫吸附测定（ELISA）来测定血清中细胞因子血管内皮生长因子（VEGF）和白细胞介素-6（IL-6）的预处理水平。研究肿瘤灌注与这些生物学标志物中的每一个之间的相关性，以及标志物之间的相互相关性。还评估了这些微环境参数的预后价值。
对于CA IX和GLUT-1，两种标志物表达均高于中位数的患者的联合评估显示与局部控制（p = 0.02）和无病生存（p = 0.04）独立相关，区域控制有趋势（p = 0.06）。在第二个亚组中，预处理血清IL-6水平高于中位数是局部控制（p = 0.009）、无病生存（p = 0.02）和总生存（p = 0.005）的唯一独立预测因素。
据我们所知，我们是第一个报道HNSCC中IL-6预处理血清水平与体内放射抗性之间联系的。这种联系得到了预处理IL-6与局部控制的强预后关联的支持，局部控制是判断放疗反应的最重要参数。此外，CA IX和GLUT-1的联合评估与预后独立相关。这有力地表明联合方法在预后标志物研究中很重要。
