Takano I, Tamura S, Yamanaka N
Department of Otolaryngology, Wakayama Medical College.
Nihon Jibiinkoka Gakkai Kaiho. 1997 May;100(5):524-33. doi: 10.3950/jibiinkoka.100.524.
We investigated the p53 expression and the presence of HPV DNA in 90 patients with squamous cell carcinomas (SCCs) of the head and neck and the relation to clinicopathological parameters and patients' prognosis. Immunohistochemical analysis of p53 protein was conducted by using monoclonal anti-p53 antibody, clone 1801 and clone 240. The relationship between the overexpression of p53 and the duration of survival of patients was analyzed. The polymerase chain reaction (PCR) was carried out with consensus primers capable of detecting HPV16, 18, 31, 33, 52b and 58. In situ hybridization was performed in the mesopharyngeal carcinoma to confirm the presence of HPV genomes in cancer cells with a wide-spectrum cDNA probe capable of detecting HPV6, 11, 16, 18, 30, 31, 33, 35, 45, 51, 52. Forty-five tissue samples (50%) were immunohistochemically positive for p53. T-category, N-category, primary site of tumor, clinical stage and tumor differentiation did not correlate with p53 expression. Our finding that p53 overexpression occurred in 50% of head and neck tumor samples is similar to the frequency of p53 overexpression reported for both lung and esophageal cancer. The common risk factor is the same in these neoplasms, and therefore it is not surprising to find a similar percentage of p53 overexpression. The prevalence of metastasis was higher in the patients with p53-positive staining than in those with p53-negative staining (p < 0.10). Analysis of cumulative survival rates of patients by the Kaplan-Meier method showed a close correlation between p53 expression and survival time. The survival differences according to p53 immunostaining were significant (p 0.05). Our results indicate that p53 immunohistochemical evaluation may be useful as one of the new prognostic parameters in head and neck cancer patients. The HPV genomes were detected in 9 of 90 patients (10.0%); 8 of 9 patients with mesopharyngeal cancer and one with maxillary cancer, namely, 29.6% of mesopharyngeal cancers and 6.7% of maxillary cancer contained HPV DNA sequences. Seven of 8 patients had SCCs of tonsil origin. Almost all of the HPV infections in our study occurred in patients with mesopharyngeal cancer, and it has been suggested that this anatomic subsite may be more frequently infected by HPV than other sites within the head and neck region. Among the 27 patients with mesopharyngeal cancer, HPV DNA-positive patients experienced a higher incidence of complete remission than HPV DNA-negative patients (87.5% vs. 26.3%, p < 0.05).
我们研究了90例头颈部鳞状细胞癌(SCC)患者中p53的表达及人乳头瘤病毒(HPV)DNA的存在情况,并分析了其与临床病理参数及患者预后的关系。采用克隆号为1801和240的单克隆抗p53抗体对p53蛋白进行免疫组织化学分析。分析p53过表达与患者生存时间的关系。采用能检测HPV16、18、31、33、52b和58的共有引物进行聚合酶链反应(PCR)。在中咽癌中进行原位杂交,用能检测HPV6、11、16、18、30、31、33、35、45、51、52的广谱cDNA探针确认癌细胞中HPV基因组的存在。45份组织样本(50%)p53免疫组织化学检测呈阳性。T分期、N分期、肿瘤原发部位、临床分期及肿瘤分化程度与p53表达均无相关性。我们发现50%的头颈部肿瘤样本中存在p53过表达,这一频率与报道的肺癌和食管癌中p53过表达频率相似。这些肿瘤的常见危险因素相同,因此p53过表达比例相似并不奇怪。p53染色阳性患者的转移发生率高于p53染色阴性患者(p<0.10)。采用Kaplan-Meier法分析患者的累积生存率,结果显示p53表达与生存时间密切相关。根据p53免疫染色的生存差异具有统计学意义(p<0.05)。我们的结果表明,p53免疫组织化学评估可作为头颈部癌患者新的预后参数之一。90例患者中有9例(10.0%)检测到HPV基因组;9例中咽癌患者中有8例,上颌癌患者中有1例,即29.6%的中咽癌和6.7%的上颌癌含有HPV DNA序列。8例患者中有7例为扁桃体来源的SCC。我们研究中几乎所有的HPV感染都发生在中咽癌患者中,有人提出该解剖亚部位可能比头颈部其他部位更易被HPV感染。在27例中咽癌患者中,HPV DNA阳性患者的完全缓解率高于HPV DNA阴性患者(87.5%对26.3%,p<0.05)。