Saito Yuki, Ushiku Tetsuo, Omura Go, Yasuhara Kazuo, Yoshida Masafumi, Takahashi Wataru, Ando Mizuo, Fukayama Masashi, Yamasoba Tatsuya
Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
ORL J Otorhinolaryngol Relat Spec. 2016;78(6):334-343. doi: 10.1159/000455901. Epub 2017 Feb 8.
The clinical significance of the Epstein-Barr virus (EBV) status and p16 expression was unknown in nasopharyngeal carcinoma (NPC).
We retrospectively studied our pathology database for 13 years to determine the prevalence of EBV and p16 expression and their association with prognosis in cases of NPC. We performed immunohistochemistry for the p16 protein and in situ hybridization (ISH) for EBV-encoded small RNAs and human papillomavirus (HPV) DNA.
Of the 43 patients with NPC, 27 (63%), 6 (14%), and 10 (23%) cases were EBV positive, EBV negative with keratinization, and EBV negative without keratinization, respectively. No cases were HPV positive by ISH. Among the 21 EBV-positive tumours that were tested for p16, only 2 tumours were p16 positive. The keratinization-positive group included only males, typically >60 years of age (5 of 6) and with T4 tumours (3 of 6). In contrast, the EBV-positive cohort tended to be younger (<60 years, 13 of 27) and have progressive N-stage tumours (N2-3, 14 of 27). The keratinization and EBV-negative cohort included predominantly males (9 of 10) who were likely p16 negative (4 of 10) and smokers (7 of 10). Multivariate analysis confirmed that keratinization was an independent prognostic factor for progression-free survival.
In areas, such as Japan, that are nonendemic for both EBV and HPV, the causality of NPC appears to be more heterogeneous.
在鼻咽癌(NPC)中,爱泼斯坦-巴尔病毒(EBV)状态和p16表达的临床意义尚不清楚。
我们回顾性研究了13年的病理数据库,以确定NPC病例中EBV和p16表达的发生率及其与预后的关系。我们对p16蛋白进行了免疫组织化学检测,并对EBV编码的小RNA和人乳头瘤病毒(HPV)DNA进行了原位杂交(ISH)检测。
43例NPC患者中,EBV阳性、EBV阴性伴角化、EBV阴性不伴角化的病例分别为27例(63%)、6例(14%)和10例(23%)。ISH检测均未发现HPV阳性病例。在检测p16的21例EBV阳性肿瘤中,只有2例p16阳性。角化阳性组仅包括男性,通常年龄>60岁(6例中的5例),且为T4期肿瘤(6例中的3例)。相比之下,EBV阳性队列往往更年轻(<60岁,27例中的13例),且有进展期N分期肿瘤(N2-3,27例中的14例)。角化和EBV阴性队列主要包括男性(10例中的9例),他们可能p16阴性(10例中的4例)且为吸烟者(10例中的7例)。多变量分析证实,角化是无进展生存期的独立预后因素。
在日本等EBV和HPV均为非地方性流行的地区,NPC的病因似乎更为异质性。