Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, Arnold-Heller-Strasse 3, Haus 27, 24105 Kiel, Germany.
Int J Oncol. 2011 Jul;39(1):185-91. doi: 10.3892/ijo.2011.1006. Epub 2011 Apr 14.
Head and neck squamous cell carcinomas (HNSCC) represent the sixth largest group among all human malignancies. However, the exact molecular mechanisms inducing the genesis and the progression of metastasis in these tumors are poorly understood. The identification of molecular alterations involved in metastasis of HNSCC might influence the value of clinical diagnostics, impact therapy strategies and finally improve the prognosis of the patients. The purpose of this study was to identify clinically relevant alterations at the transcriptional and translational levels, when comparing metastatic (N+) and non-metastatic (N0) primary HNSCC. Three transcripts HERPUD1, SLPI and RAD51 were selected for further validation based on their association with carcinogenesis and metastasis. Quantitative real-time-PCR was performed to determine the mRNA expression levels. For subsequent confirmation of the results, immunohistochemistry was performed applying a monoclonal anti-SLPI antibody on 121 HNSCC tumor specimens (N0, n=40; N+, n=81). In metastatic primary cancer, SLPI mRNA showed 5.9-fold lower expression in comparison with non-metastatic primary cancer (p=0.0092). Immunohistochemical staining revealed a fold change of -1.79 between the N+ and the N0 group (p=0.0002). The results presented here clearly indicate the repression of SLPI, measurable on both, mRNA and protein levels in metastatic primary HNSCC as compared to non-metastatic HNSCC. Therefore, it can be assumed that SLPI might have a substantial protective effect on the metastasis process of HNSCC.
头颈部鳞状细胞癌(HNSCC)是人类所有恶性肿瘤中第六大常见类型。然而,导致这些肿瘤发生和转移的确切分子机制仍知之甚少。鉴定与 HNSCC 转移相关的分子改变可能会影响临床诊断的价值、影响治疗策略,并最终改善患者的预后。本研究旨在比较转移性(N+)和非转移性(N0)原发性 HNSCC 时,在转录和翻译水平上确定具有临床意义的改变。基于其与癌变和转移的相关性,选择了三个转录本 HERPUD1、SLPI 和 RAD51 进行进一步验证。通过定量实时 PCR 确定 mRNA 表达水平。为了进一步证实结果,应用抗 SLPI 单克隆抗体对 121 例 HNSCC 肿瘤标本(N0,n=40;N+,n=81)进行了免疫组织化学检测。与非转移性原发性癌症相比,转移性原发性癌症中的 SLPI mRNA 表达水平低 5.9 倍(p=0.0092)。免疫组织化学染色显示 N+组和 N0 组之间的 fold change 为-1.79(p=0.0002)。本研究结果清楚地表明,与非转移性 HNSCC 相比,转移性原发性 HNSCC 中 SLPI 的表达在 mRNA 和蛋白水平上均受到抑制。因此,可以假设 SLPI 可能对头颈部鳞状细胞癌的转移过程具有实质性的保护作用。