Bradford C R, Zhu S, Wolf G T, Poore J, Fisher S G, Beals T, McClatchey K D, Carey T E
University of Michigan, Ann Arbor, USA.
Otolaryngol Head Neck Surg. 1995 Oct;113(4):408-12. doi: 10.1016/s0194-5998(95)70077-3.
A critical research frontier in head and neck oncology involves defining the use of induction chemotherapy regimens to allow organ preservation and to avoid functionally debilitating surgical resections. Completed clinical trials in laryngeal cancer indicate that such an approach is feasible, but progress thus far has been limited by our inability to predict which patients are likely to respond to chemotherapy and preserve their larynx. Mutation of the p53 tumor-suppressor gene is the most common genetic alteration identified thus far in human cancers, and it may be important in regulation of cell proliferation and chemosensitivity. To determine whether p53 overexpression predicts chemotherapy response, organ preservation, and survival in patients with advanced laryngeal cancer, we analyzed immunohistologic expression of p53 in tissue sections from 178 patients with advanced laryngeal cancer who were entered in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multiinstitutional clinical trial comparing induction chemotherapy (cis-platinum and 5-fluorouracil) plus radiation therapy (94 patients) to surgery plus postoperative radiation therapy (84 patients). Larynx preservation was significantly higher in the group of patients whose tumors overexpressed p53 (74% vs. 52.5%; p = 0.03). The presence of p53 overexpression did not predict survival in either the surgery or the chemotherapy groups (p = 0.82 and p = 0.53).
头颈肿瘤学领域一个关键的研究前沿是确定诱导化疗方案的使用，以实现器官保留并避免造成功能衰弱的手术切除。喉癌的已完成临床试验表明，这种方法是可行的，但迄今为止，由于我们无法预测哪些患者可能对化疗有反应并保留其喉部，进展有限。p53肿瘤抑制基因的突变是迄今为止在人类癌症中发现的最常见的基因改变，它可能在细胞增殖和化疗敏感性的调节中起重要作用。为了确定p53过表达是否能预测晚期喉癌患者的化疗反应、器官保留情况和生存率，我们分析了178例晚期喉癌患者组织切片中p53的免疫组织化学表达，这些患者参加了退伍军人事务部喉癌合作研究，这是一项多机构临床试验，比较诱导化疗（顺铂和5-氟尿嘧啶）加放射治疗（94例患者）与手术加术后放射治疗（84例患者）。肿瘤过表达p53的患者组中喉保留率显著更高（74%对52.5%；p = 0.03）。p53过表达的存在在手术组或化疗组中均不能预测生存率（p = 0.82和p = 0.53）。
