Muller Susan, Su Ling, Tighiouart Mourad, Saba Nabil, Zhang Hongzheng, Shin Dong M, Chen Zhuo Georgia
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Cancer. 2008 Jul 1;113(1):97-107. doi: 10.1002/cncr.23557.
The authors investigated whether coexpression and localization of E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) had predictive and/or prognostic correlations with lymph node metastasis and/or survival in patients with squamous cell carcinoma of the head and neck (SCCHN).
Immunohistochemistry (IHC) of archival tissue was performed to measure expression of EGFR and E-cad in surgical specimens of SCCHN (n = 143) that included primary tumors (PTs) with positive lymph nodes (Tu+Met) and their paired lymph node metastases (LnMet), PTs with negative lymph nodes (Tu(-Met)), and benign tissue biopsies as normal controls. IHC staining was quantified as a weighted index and as the ratio of membrane to cytoplasmic staining. Correlative expression between EGFR and E-cad also was examined in SCCHN cell lines by immunoblotting and immunofluorescence analyses.
Three distinct expression patterns of EGFR and E-cad were observed. Membrane localization of E-cad was significantly lower in the Tu+Met group than in the Tu(-Met) group (P = .01) and was associated inversely with lymph node status (P = .009). Wilcoxon analysis of the combined markers demonstrated that expression and/or membrane localization of EGFR and E-cad were correlated with disease-free survival and overall survival in patients with SCCHN. The study of SCCHN cell lines demonstrated that cells with positive but low EGFR expression and with negative E-cad expression were relatively resistant to the EGFR tyrosine kinase inhibitor erlotinib.
The current study suggested that examining not only the expression but also the localization of EGFR and E-cad simultaneously may have clinical relevance in predicting lymph node metastasis, patient survival, and response to EGFR-targeted therapy in patients with SCCHN.
作者研究了E-钙黏蛋白（E-cad）和表皮生长因子受体（EGFR）的共表达及定位与头颈部鳞状细胞癌（SCCHN）患者淋巴结转移和/或生存之间是否存在预测性和/或预后相关性。
对存档组织进行免疫组织化学（IHC）检测，以测量SCCHN手术标本（n = 143）中EGFR和E-cad的表达，这些标本包括伴有阳性淋巴结的原发性肿瘤（PTs）（肿瘤伴转移，Tu+Met）及其配对的淋巴结转移灶（LnMet）、伴有阴性淋巴结的PTs（肿瘤无转移，Tu(-Met)），以及作为正常对照的良性组织活检标本。IHC染色定量为加权指数以及膜染色与胞质染色的比值。还通过免疫印迹和免疫荧光分析在SCCHN细胞系中检测EGFR和E-cad之间的相关表达。
观察到EGFR和E-cad三种不同的表达模式。E-cad的膜定位在Tu+Met组显著低于Tu(-Met)组（P = 0.01），并且与淋巴结状态呈负相关（P = 0.009）。对联合标志物的Wilcoxon分析表明，EGFR和E-cad的表达和/或膜定位与SCCHN患者的无病生存期和总生存期相关。对SCCHN细胞系的研究表明，EGFR表达阳性但水平低且E-cad表达阴性的细胞对EGFR酪氨酸激酶抑制剂厄洛替尼相对耐药。
当前研究表明，同时检测EGFR和E-cad的表达及定位可能在预测SCCHN患者的淋巴结转移、患者生存以及对EGFR靶向治疗的反应方面具有临床意义。
