p14ARF、p53蛋白表达与H101治疗鼻咽癌疗效的关系

目的：观察肿瘤组织p14^ARF、突变型p53蛋白表达状态与E1B缺陷型腺病毒治疗鼻咽癌疗效的关系，探讨E1B缺陷型腺病毒（简称H101）基因治疗的作用机制。方法：应用免疫组织化学方法对36例H101治疗的晚期鼻咽鳞癌病例进行肿瘤组织p14^ARF、突变型p53蛋白检测，分析肿瘤组织p14^ARF、突变型p53蛋白表达与H101临床疗效的关系；结果：突变型p53和p14^ARF蛋白在36例晚期鼻咽鳞癌中总阳性表达率分别为55．6％和44．4％；突变型p53^＋p14^ARF（即p14^ARF蛋白无缺失）患者均无治疗有效病例；突变型p53^＋p14^ARF-（即p14^ARF蛋白有缺失）患者中有4例有效；结论：对于p53基因无突变的恶性肿瘤，p14ARF基因缺失可能是H101能在肿瘤细胞内有效复制并杀死肿瘤细胞的一个重要影响因素。

Relationship between the expressions of p14ARF and p53 proteins and the therapeutic efficacy of H101 on nasopharyngeal carcinoma

Objective: To investigate the relationship between the expressions of p14ARF and p53 protein and the therapeutic efficacy of E1B-deleted adenovirus(H101) on nasopharyngeal carcinoma and to explore the mechanism of the action of H101.Methods: The expressions of p14ARF and p53 proteins in 36 cases of advanced nasopharyngeal carcinoma were detected by immunohistochemical method.The relationship between the expression of p14ARF and mutant p53 protein and the therapeutic efficacy of H101 were analyzed.Results: The total positive rates of mutant p53 and p14ARF proteins were 55.6%(20/36)and 44.4%(16/36)in advanced nasopharyngeal carcinoma,respectively.The total response rate of 36 patients after treated with H101 was 47.1%.Patients with positive p53 and p14ARF expressions(p53+p14ARF+) had no response to H101 treatment.H101 treatment was effective in 4 patients with positive p53 protein expression and negative p14ARF expression(p53+p14ARF+).Conclusion: The loss of p14ARF gene is an important factor for tumor-killing action of H101 on malignant tumor cells with no p53 gene mutation.