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

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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