PDF(Pubmed)
Abstract：
The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the \"classical\" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.
摘要：
场癌化理论是头颈部癌的重要范例，因为其肿瘤影响以多种方式影响治疗结果。这项研究的目的是评估肿瘤周围粘膜与肿瘤新血管生成过程之间可能的相互联系。本研究纳入了60例晚期喉癌患者。大多数患者表达典型的HIF上调的促血管生成特征,HIF-1α过表达和HIF-2α同种型的正常表达水平几乎完全占优势。值得注意的是,在肿瘤周围良性粘膜中,超过60%的队列也显示出HIF上调的促血管生成特征.此外,与肿瘤组织相比，后一个亚组的HIF-2α上调表型明显偏移，即，与由HIF-1α肿瘤表型主导的情况相反,观察到HIF开关的趋势。ETS-1在肿瘤和肿瘤周围粘膜中存在的促血管生成表型中均显示稳定且相同的显着过表达。在目前的研究中,我们首次报道了与成对的远端喉粘膜相比，晚期喉癌瘤周粘膜中存在异常的促血管生成表达谱。此外，我们描述了这种促血管生成特征的特定表型，该表型与肿瘤组织中存在的表型显着不同，因为我们描述了两种表型，定量和定性。这个发现是癌症的异质性，本身，超出了恶性肿瘤的“经典”边界，这证明了场癌变和癌症的经典标志之一——肿瘤新血管生成的过程之间有很强的联系。
