Distinctive E-cadherin and epidermal growth factor receptor expression in metastatic and nonmetastatic head and neck squamous cell carcinoma - Predictive and prognostic correlation
Distinctive E-cadherin and epidermal growth factor receptor expression in metastatic and nonmetastatic head and neck squamous cell carcinoma - Predictive and prognostic correlation
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DOI：
10.1002/cncr.23557
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发表时间：
2008-07-01
期刊：
影响因子：
6.2
通讯作者：
(Georgia) Chen, Zhuo
中科院分区：
文献类型：
--
作者：
Muller, Susan;Su, Ling;(Georgia) Chen, Zhuo
背景资料。方法采用免疫组织化学(IHC)法检测143例头颈部鳞状细胞癌手术标本中E-钙粘蛋白(E-cad)和表皮生长因子受体(EGFR)的表达情况，包括原发灶(PTS)淋巴结阳性(Tu(+Met))及其配对淋巴结转移(LnMet)，良性组织活检作为正常对照。IHC染色作为加权指标和细胞膜/胞浆染色的比率进行量化。免疫印迹和免疫荧光分析检测了EGFR和E-cad在SCCHN细胞中的表达相关性。Tu(+Met)组E-cad的膜定位明显低于Tu(-Met)组(P=0.01)，且与淋巴结状况呈负相关(P=0.009)。联合市场的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细胞株的研究表明，EGFR表达阳性但低表达的细胞和E-cad表达阴性的细胞对EGFR酪氨酸激酶抑制剂erlotinib相对耐药。结论本研究提示，同时检测EGFR和E-cad的表达和定位可能对预测SCCHN患者的淋巴结转移、患者生存和EGFR靶向治疗的疗效具有临床意义。
BACKGROUND. 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).METHODS. 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.RESULTS. 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 markets 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.CONCLUSIONS. 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.