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[头颈部鳞状上皮癌中的p53突变与HPV感染。长期随访]

[p53 mutations and HPV infections in squamous epithelial carcinomas of the head-neck region. Long-term follow-up].

作者信息

Riethdorf S, Friedrich R E, Sühwold J, Ostwald C, Barten M, Gogacz P, Gundlach K K, Schlechte H, Becker J, Bregenzer T, Riethdorf L, Löning T

机构信息

Abteilung für Oralchirurgie und zahnärztliche Röntgenologie, Zentrum für Zahnmedizin, Universitätsklinikum Charité, Berlin.

出版信息

Mund Kiefer Gesichtschir. 1998 Jan;2(1):30-4. doi: 10.1007/s100060050024.

Abstract

Mutations of the p53 gene are the most commonly observed genetic alterations in malignant tumors and are often associated with a loss of the tumor suppressor function of the p53 protein. We have analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations and 92 of them additionally for human papillomavirus (HPV) infection in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Using the method of polymerase chain reaction (PCR)/temperature gradient gel electrophoresis (TGGE), mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed missense mutations in most cases (15/20). Frequency of p53 gene mutations was not related to the tumor stage, the grade of differentiation, the presence of lymph node metastases, or the smoking history of the patients. With the help of a highly sensitive PCR/hybridization assay, an infection with the high-risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99 patients with a range of 2-112 months. No correlation of overall survival on the presence of p53 gene mutations or HPV infection could be observed. The absence of statistically significant correlations between p53 gene mutations and progressive disease, however, does not exclude its putative relevance in early phases of tumor development.

摘要

p53基因的突变是恶性肿瘤中最常见的基因改变,并且常常与p53蛋白的肿瘤抑制功能丧失相关。我们分析了110例头颈部鳞状细胞癌(HNSCC)患者的标本以检测p53基因突变,其中92例还检测了人乳头瘤病毒(HPV)感染情况,以便通过与临床随访数据比较来评估这些因素的预后意义。采用聚合酶链反应(PCR)/温度梯度凝胶电泳(TGGE)方法,在48个肿瘤(44%)中发现了p53基因第5至8外显子的突变。测序显示大多数病例(15/20)存在错义突变。p53基因突变频率与肿瘤分期、分化程度、淋巴结转移情况或患者吸烟史无关。借助高灵敏度的PCR/杂交检测法,在92个肿瘤标本中的39个(42%)检测到了高危型HPV 16和18感染。从99例患者获得了随访数据,随访时间为两个月至112个月。未观察到p53基因突变或HPV感染与总生存率存在相关性。然而,p53基因突变与疾病进展之间缺乏统计学显著相关性并不排除其在肿瘤发生早期阶段的假定相关性。

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