Prognostic role of Ebstein-Barr virus latent membrane protein-1 and Interleukin-10 expression in patients with nasopharyngeal carcinoma
Prognostic role of Ebstein-Barr virus latent membrane protein-1 and Interleukin-10 expression in patients with nasopharyngeal carcinoma
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DOI：
10.1081/cnv-200026386
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发表时间：
2004-01-01
影响因子：
2.4
通讯作者：
Atahan, IL
中科院分区：
文献类型：
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作者：
Özyar, E;Ayhan, A;Atahan, IL
目的：目的探讨EB病毒潜伏膜蛋白-1（LMP-1）和白细胞介素-10（IL-10）在鼻咽癌（NPC）中的表达及其与预后的关系。材料与方法：1993年至1999年，166例非转移性鼻咽癌患者在我科接受治疗。采用免疫组化方法检测了74例（男53例，女21例）乳腺癌石蜡包埋组织中LMP-1和IL-10的表达。进行了详细的组织病理学分析，包括细胞凋亡和淋巴细胞浸润的程度，并根据世界卫生组织（WHO）的分类对所有患者进行了重新分类。使用所有临床和病理预后因素进行单变量、多变量和logistic回归分析。所有患者均接受放疗+/-化疗。随访时间范围为12至80个月（中位数：32）。结果：病理诊断为WHO-I级1例（1.3%），WHO-II级15例（20.2%），WHO-III级58例（79.5%）。IL-10阳性表达38例（51%），LMP-1阳性表达44例（61%）。27例（36.4%）患者同时检测到IL-10和LMP-1。与LMP-1阳性患者相比，无LMP-1表达的患者的NO疾病显著更多（65%对35%，p = 0.01）。Logistic回归分析显示，晚期淋巴结受累是影响IL-10表达的主要参数（p = 0.03）。全组的3年总生存率（OS）、局部无复发生存率（LRRFS）和无远处转移生存率（DMFS）分别为67.8%、84.4%和74.3%。在单变量分析中，WHO-III患者的LRRFS显著较低，晚期淋巴结疾病和IL-10阴性患者的DMFS显著较低，WHO-III患者的OS显著较低。多因素分析显示，WHO-III和T2患者与较低的OS显著相关，N3患者与较低的DMFS显著相关。结论：我们观察到高比率（61%）的EB病毒（LMP-1阳性）和NPC的关联在我们的患者。发现LMP-1阳性肿瘤更易于侵袭淋巴结。IL-10表达阴性的患者有更晚期的N病。在多变量分析中，我们没有发现IL-10和EBV LMP-1对生存的预后显著作用。
Purpose: We aimed to investigate Ebstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) and Interleukine-10 (IL-10) expression in nasopharyngeal carcinoma (NPC) patients and to evaluate their prognostic significance. Material and Methods: Between 1993 and 1999, 166 patients were treated with the diagnosis of nonmetastatic NPC at our department. The expression of LMP-1 and IL-10 was investigated by using an immunohistochemical approach in 74 (53 male, 21 female) patients whose paraffin embedded tissue samples were available. A detailed histopathological analysis including degree of apoptosis and lymphocyte infiltration was made and all patients were reclassified according to the World Health Organization (WHO) classification. Univariate, multivariate, and logistic regression analyses were performed using all clinical and pathological prognostic factors. All patients were treated with radiotherapy +/-chemotherapy. Follow-up ranged between 12 and 80 months (median: 32). Results: The histopathological diagnosis was WHO-I in 1 (1.3%), WHO-II in 15 (20.2%), and WHO-III in 58 (79.5%) patients. There were 38 (51%) patients with IL-10 expression and 44 (61%) patients with LMP-1 expression. Twenty-seven (36.4%) patients were found to be both IL-10 and LMP-1 positive. There were significantly more NO disease in patients without LMP-1 expression compared to LMP-1 positive patients (65% vs. 35%, p = 0.01). The logistic regression analysis showed advanced nodal involvement to be the major parameter affecting the expression of IL-10 (p = 0.03). Three-year overall survival (OS), locoregional relapse free survival (LRRFS), and distant metastasis free survival (DMFS) rates were 67.8%, 84.4%, and 74.3%, respectively, for the whole group. On univariate analysis, LRRFS was significantly lower in WHO-III patients, DMFS was significantly lower in advanced nodal disease and IL-10 negative patients, and OS was significantly lower in WHO-III patients. Multivariate analysis showed that WHO-III and T2 patients were significantly associated with lower OS and N3 patients were significantly associated with lower DMFS. Conclusion: We observed a high rate (61%) of EBV (LMP-1 positive) and NPC association in our patients. LMP-1 positive tumors were found to be more prone to invade lymph nodes. Patients with negative IL-10 expression had more advanced N disease. We did not find a prognostic significant role of IL-10 and EBV LMP-1 on survival in multivariate analysis.