Radiation Oncology Department, Oncology Hospital, Centro Medico Nacional Siglo XXI (IMSS), Mexico, D.F., Mexico.
Pathology Department, National Cancer Institute of Mexico (INCan), Mexico, D.F., Mexico.
Arch Med Res. 2014 Apr;45(3):229-36. doi: 10.1016/j.arcmed.2014.02.002. Epub 2014 Mar 4.
Although the latent membrane protein type 1 (LMP1) is frequently expressed in Epstein-Barr virus (EBV) malignancies, its contribution to the pathogenesis of nasopharyngeal carcinoma (NPC) is not fully defined. LMP1 functions as a viral mimic of the TNFR family member engaging a number of signaling pathways that induce morphological and phenotypic alterations. This study aimed to investigate the LMP1 expression and EBV infection in relation to clinical outcome and survival in a series of Mexican NPC patients. We also studied expression of p16 and p53 proteins.
We analyzed in 25 tumor specimens the expression of LMP1, p16 and p53 by immunohistochemistry (IHC) and EBV presence by IHC/in situ hybridization. Differences in clinical outcome and survival in relation to protein expression were correlated through χ(2) statistics and Kaplan-Meier survival curves.
Our results showed a rate of 92% (23/25) of EBV infection. The expressions of LMP-1, p16 and p53 proteins were 40.0, 44.0 and 40.0%, respectively. LMP-1 immunoexpression was more common in older patients (>50 vs. <50 years old, p = 0.02) and with parapharyngeal space invasion (p = 0.02). The presence of metastatic disease at diagnosis (p = 0.03), distant recurrence disease (p = 0.006) and shorter distance recurrence-free survival (p = 0.05) was associated with lack of p16.
In our series, EBV infection rates are particularly high for nonendemic NPC, although without a statistically significant difference in overall survival, LMP1 and p16 expression was correlated with poorer clinical prognosis. Probably, LMP1 and p16 detection identify a worse clinical prognosis in NPC patient subgroup.
尽管潜伏膜蛋白 1(LMP1)在 Epstein-Barr 病毒(EBV)恶性肿瘤中经常表达,但它对鼻咽癌(NPC)发病机制的贡献尚未完全确定。LMP1 作为 TNFR 家族成员的病毒模拟物发挥作用,涉及许多诱导形态和表型改变的信号通路。本研究旨在调查一系列墨西哥 NPC 患者中 LMP1 表达和 EBV 感染与临床结果和生存的关系。我们还研究了 p16 和 p53 蛋白的表达。
我们通过免疫组织化学(IHC)分析了 25 个肿瘤标本中 LMP1、p16 和 p53 的表达,并通过 IHC/原位杂交分析了 EBV 的存在。通过 χ(2)统计和 Kaplan-Meier 生存曲线,比较了蛋白表达与临床结果和生存的差异。
我们的结果显示 EBV 感染率为 92%(23/25)。LMP-1、p16 和 p53 蛋白的表达率分别为 40.0%、44.0%和 40.0%。LMP-1 免疫表达在年龄较大的患者(>50 岁与<50 岁,p = 0.02)和咽旁间隙侵犯(p = 0.02)中更为常见。诊断时存在转移性疾病(p = 0.03)、远处复发疾病(p = 0.006)和较短的远处无复发生存(p = 0.05)与缺乏 p16 相关。
在我们的系列中,非地方性 NPC 的 EBV 感染率特别高,尽管总体生存率无统计学差异,但 LMP1 和 p16 的表达与较差的临床预后相关。可能,LMP1 和 p16 的检测可识别 NPC 患者亚组的不良临床预后。