MOLECULAR-BIOLOGICAL APPROACHES TO HEAD AND NECK CANCER AND THE CLINICAL APPLICATION

1. 间咽癌中p53改变的多因素分析：采用免疫组织染色法检测p53蛋白。26例肿瘤中有15例（62%）存在显著过表达。在临床III期和IV期，p53过表达患者的5年总生存率为0%，而阴性患者的5年总生存率为41.7%。采用elisa法检测了中咽癌患者血清中p53抗体的含量，40%的患者血清中p53抗体呈阳性。血清学分析是有利的，因为它不需要肿瘤样本。此外，还可用于患者的随访。粘附分子、蛋白水解酶和血管生成因子在头颈癌转移中的意义：头颈癌组织中E-cadherin表达及其与生存率的关系研究显示，E-cadherin表达降低与预后不良相关。因此，e -钙粘蛋白的功能可能与肿瘤细胞的转移活性密切相关。血管生成是转移性菌落扩张和肿瘤生长所必需的。来源于头颈部癌细胞的细胞系显示出大量血管内皮生长因子（VEGF）的产生，这是一种最常见的血管生成因子，表明肿瘤细胞为自身生长诱导血管生成。结合免疫组织化学技术和计算机图像分析清楚地表明微血管密度是头颈部肿瘤远处转移的重要预后因素。通过抗E-cadherin抗体抑制E-cadherin功能可上调VEGF的产生，这有力地支持了E-cadherin功能与血管生成的密切关系。ELISA法检测头颈癌患者血清中可溶性E-cadherin水平，发现可溶性E-cadherin水平升高与预后不良密切相关。这些数据强烈提示血清可溶性e -钙粘蛋白可能是预测远处转移非常有用的参数。少

1. Multifactorial analysis of p53 alteration in mesopharyngeal carcinoma : Immunohistological staining for the detection of p53 protein was performed. Significant overexpression was observed in 15 of 26 tumors (62%). In clinical stages III and IV, a five-year overall survival of patients with p53 overexpression was 0%, showing apparent contrast to 41.7% for the negative patients. A p53 antibody in the sera of mesopharyngeal carcinoma patients was measured by ELISA.4O% of the patients were positive for p53 antibody. Serological analysis is advantageous because it does not require tumor samples. Furthermore, it can be used for the follow-up of patients.2. Implication of adhesion molecules, proteolytic enzymes and angiogenic factors in head and neck cancer metastasis : Study of E-cadherin expression in head and neck cancer tissues and its relation with survival rate revealed that decreased E-cadherin expression was correlated with poor prognosis. Thus, the function of E-cadherin may be cl … More osely related with metastatic activity of tumor cells. Angiogenesis is required for expansion of metastatic colonies as well as tumor growth. Cell lines derived from head and neck cancer cells showed significant production of vascular endothelial growth factor (VEGF), a most common angiogenic factor, indicating that tumor cells induce angiogenesis for their own growth. Combination of the immunohistochemical technique and computer-image analysis clearly showed that microvascular density was an important prognostic factor for distant metastasis in head and neck cancer. Suppression of E-cadherin function by anti-E-cadherin antibody upregulated the production of VEGF, which strongly support the close relationship between E-cadherin function and angiogenesis. Evaluation of soluble E-cadherin in sera of head and neck cancer patients by ELISA revealed that an increase of soluble E-cadherin closely related to poorer prognosis. The data strongly suggest that serum soluble E-cadherin may be very useful parameter predicting distant metastasis. Less