The association between elevated EphB4 expression, smoking status, and advanced-stage disease in patients with head and neck squamous cell carcinoma

The association between elevated EphB4 expression, smoking status, and advanced-stage disease in patients with head and neck squamous cell carcinoma
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DOI:
10.1001/archotol.132.10.1053
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发表时间:
2006-10-01
影响因子:
--
通讯作者:
Gill, Parkash S.
Gill, Parkash S.
中科院分区:
其他
文献类型:
--
作者:
Sinha, Uttam K.;Mazhar, Kashif;Gill, Parkash S.

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目的:检测头颈鳞状细胞癌(HNSCC)患者肿瘤组织、周围正常组织和转移淋巴结中EphB4的表达,并评估其与疾病分期和吸烟的关系。设计:回顾性研究。地点:南加州大学-大学医院、南加州大学洛杉矶县医学中心、南加州大学洛杉矶分校耳鼻喉科-头颈外科。患者:48名不同分期的患者HNSCC(I-IV)的患者被纳入本研究。分期依据美国癌症联合委员会的分期系统。主要指标:通过免疫组化、Western blot、实时聚合酶链反应评估肿瘤组织、周围正常组织和转移淋巴结中EphB4的表达情况。然后根据疾病分期和吸烟状况比较患者之间EphB4的表达情况。结果:HNSCC患者的所有肿瘤标本和转移淋巴结中均检测到EphB4表达,但转移淋巴结中表达水平较高。与初发疾病患者(I 或 II 期)相比,晚期疾病患者(III 期或 IV 期)以及吸烟者与非吸烟者相比,晚期疾病患者(III 期或 IV 期)的平均 EphB4 蛋白表达和 EphB4 基因扩增均具有统计学上显着较高的差异。结论:EphB4 过度表达与晚期 HNSCC 以及吸烟患者相关。这些数据首次证明了 EphB4 与 HNSCC 疾病晚期和吸烟之间的关联,因此为针对 EphB4 进行 HNSCC 治疗提供了强有力的理由。
Objective: To examine the expression of EphB4 in tumor tissue, surrounding normal tissue, and metastatic lymph node in patients with head and neck squamous cell carcinoma ( HNSCC) and to evaluate its association with disease stage and smoking.Design: A retrospective study.Setting: University of Southern California - University Hospital, University of Southern California and Los Angeles County Medical Center, and Department of Otolaryngology - Head and Neck Surgery, University of Southern California, Los Angeles.Patients: Forty- eight patients with different stages of HNSCC ( I- IV) were enrolled into this study. Staging was based on the staging system of the American Joint Committee on Cancer.Main Outcome Measures: EphB4 expression in tumor tissue, surrounding normal tissue, and metastatic lymph node was evaluated by immunohistochemical analysis, Western blot, and real- time polymerase chain reaction. EphB4 expression was then compared between patients based on disease stage and smoking status.Results: EphB4 expression was detected in all tumor specimens and metastatic lymph nodes of patients with HNSCC, but expression levels were higher in the metastatic lymph nodes. There was a statistically significantly higher mean EphB4 protein expression and EphB4 gene amplification in patients with advanced disease ( stage III or IV) vs patients with initial disease ( stage I or II) and in smokers vs nonsmokers.Conclusions: Overexpression of EphB4 is associated with advanced stages of HNSCC as well as with patients who smoke. These data are the first to demonstrate the association of EphB4 with advanced stages of disease and smoking in HNSCC and hence provide a strong rationale for targeting EphB4 for HNSCC therapies.