Awwad S, Jaros E, Somes J, Lunec J
Northern Center for Cancer Treatment, Newcastle General Hospital, Newcastle Upon Tyne, UK.
Int J Radiat Oncol Biol Phys. 1996 Jan 15;34(2):323-32. doi: 10.1016/0360-3016(95)02108-6.
P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy.
Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors.
Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p << 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02).
The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.
p53基因突变是人类癌症中常见的基因变化,并且有大量证据表明p53状态可能决定肿瘤对治疗的反应。本研究旨在调查接受根治性放疗的头颈癌患者中p53蛋白积累(过表达)与预后不良之间是否存在任何相关性。
对1989 - 1990年确诊并接受根治性放疗的79名头颈癌患者进行回顾性研究。使用针对人p53蛋白的小鼠单克隆抗体(D0 - 7)通过免疫组织化学染色(IHC)研究存档材料中的石蜡切片。对可能的预后因素进行局部区域肿瘤控制和患者生存的单因素和多因素分析。
42名(53%)患者的肿瘤免疫组织化学染色呈阳性。53%的喉癌、64%的口咽癌和43%的口腔癌显示p53过表达。所有伴有血管、淋巴管和/或肌膜浸润的肿瘤标本均显示p53过表达。低分化肿瘤中肿瘤染色细胞核的比例高于高分化和中分化肿瘤(p < 0.05),但与患者总体或无病5年精算生存率无关。肿瘤有p53免疫染色的患者与无免疫染色的患者在5年精算生存率和无病生存率方面无差异(分别为59%对65%和57%对51%)。TNM肿瘤分期是最显著的预后因素,早期5年精算生存率为87%,晚期为14%(p << 0.0001)。免疫染色与吸烟史之间存在显著相关性(p = 0.02)。
数据表明,在一组头颈癌中通过免疫组织化学染色检测到的p53积累并不能预测患者的不良生存或无病生存。多因素统计分析表明TNM肿瘤分期是唯一显著的预后因素。p53积累与吸烟之间存在显著关联。