Gouveris Panagiotis, Weinberger Paul M, Psyrri Amanda
Division of Hematology Oncology, Department of Internal Medicine, Yale University, New Haven, CT, USA.
Methods Mol Biol. 2010;632:239-50. doi: 10.1007/978-1-60761-663-4_15.
HPV-positive oropharyngeal squamous cell carcinomas (OSCC) represent a distinct disease entity from traditional OSCC. We hypothesized that for HPV DNA-positive cases, p16 expression status differentiates the biologically relevant ones.We determined HPV16DNA viral load in a cohort of 79 oropharyngeal squamous cell cancers by real-time polymerase chain reaction (PCR). We used cervical cancer as a disease model for HPV-initiated epithelial cancer. In cervical cancer, p53 and Rb expression is reduced, while p16 expression is increased. We used TMA technology to facilitate interrogation of this cohort for p53, Rb, and p16 protein expression using a quantitative, in situ method of protein analysis (AQUA analysis). Our results indeed delineate three biologically and clinically distinct types of oropharyngeal squamous cell cancers based on HPV-DNA determination and p16 expression status: one class of HPV-negative/p16-nonexpressing (HPV-negative), one class of HPV-positive/p16-nonexpressing (HPV-inactive), and one class of HPV positive/p16-expressing (HPV-active) oropharyngeal tumors. We demonstrated that only the HPV-active tumors share a similar molecular phenotype to cervical cancers, and are the ones associated with favorable prognosis.
人乳头瘤病毒(HPV)阳性的口咽鳞状细胞癌(OSCC)是一种有别于传统OSCC的独特疾病实体。我们推测,对于HPV DNA阳性病例,p16表达状态可区分具有生物学相关性的病例。我们通过实时聚合酶链反应(PCR)测定了79例口咽鳞状细胞癌患者队列中的HPV16 DNA病毒载量。我们将宫颈癌作为HPV引发的上皮癌的疾病模型。在宫颈癌中,p53和Rb表达降低,而p16表达增加。我们使用组织微阵列(TMA)技术,通过定量原位蛋白质分析方法(AQUA分析)对该队列进行p53、Rb和p16蛋白表达检测。我们的结果确实根据HPV-DNA测定和p16表达状态,划分出三种生物学和临床特征均不同的口咽鳞状细胞癌类型:一类是HPV阴性/p16不表达(HPV阴性),一类是HPV阳性/p16不表达(HPV无活性),还有一类是HPV阳性/p16表达(HPV有活性)的口咽肿瘤。我们证明,只有HPV有活性的肿瘤与宫颈癌具有相似的分子表型,且与良好预后相关。