Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry
Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry
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DOI：
10.1038/modpathol.3800041
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发表时间：
2004-04-01
期刊：
影响因子：
7.5
通讯作者：
Tan, DF
中科院分区：
文献类型：
--
作者：
Deeb, G;Wang, JM;Tan, DF
E-钙粘蛋白（E-cad）和表皮生长因子受体（EGFR）是重要的细胞粘附和信号通路介质。本研究旨在评估它们在肺腺癌（AdC）和鳞状细胞癌（SCC）中的表达及其与临床病理变量的关联。使用高密度组织微阵列总共研究了 130 例可切除肺癌（I-IIIA 期）。使用 Beecher 系统将每个案例中的两到三个核心排列成三个块。使用抗生物素蛋白-生物素复合物方法和针对 E-cad 和 EGFR 的单克隆抗体进行免疫组织化学分析。 > 10% 的肿瘤细胞中明确的膜染色被认为是 E-cad 和 EGFR 的阳性表达。根据临床病理变量（年龄、性别、吸烟状况、体能状态、体重减轻、组织学、分级、分期和淋巴结受累）和患者生存率分析标志物表达和共表达。分别有 118、126 和 115 例病例可完全评估 E-cad、EGFR 和两种标志物。 E-cad阳性（+）65例（55%），阴性（-）53例（45%）；阴性组23例仅胞浆染色。对于 EGRF，43 例（34%）为（+），83 例（66%）为（-）。除 EGFR(+) 与 SCC 组织学类型之间的关联外，E-cad 或 EGFR 与任何临床病理学变量之间均无显着关联。 E-cad 阴性染色和细胞质染色均与患者生存期缩短相关，P 分别为 0.008 和 0.002。 EGFR 表达与患者生存率无关；然而，E-cad(-)/EGFR(+)表型患者的生存率低于E-cad(+)/EGFR(-)患者(P=0.026)。我们的研究表明，肺 AdC 和 SCC 可以根据 E-cad 和 EGFR 的表达进行分层，其中 E-cad(-)/EGFR(+) 表达的疾病结果更差。此外，E-cad 的细胞质表达可能代表该蛋白与致瘤性相关的定位改变。
E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) are important cell adhesion and signaling pathway mediators. This study aimed to assess their expression in lung adenocarcinoma (AdC) and squamous cell carcinoma (SCC) and their association with clinicopathologic variables. In all, 130 resectable lung cancers (stages I-IIIA) were studied using a high-density tissue microarray. Two to three cores from each case were arrayed into three blocks using a Beecher system. Immunohistochemistry was performed using an avidin-biotin complex method and monoclonal antibodies against E-cad and EGFR. Unequivocal membrane staining in > 10% of tumor cells was considered as a positive expression of E-cad and EGFR. Markers expression and coexpression were analyzed against clinicopathologic variables (age, gender, smoking status, performance status, weight loss, histology, grade, stage, and lymph node involvement) and patient survival. There were 118, 126, and 115 cases that were fully assessable for E-cad, EGFR, and both markers, respectively. For E-cad, 65 cases (55%) were positive (+), 53 (45%) were negative (-); 23 cases of the negative group had only cytoplasmic staining. For EGRF, 43 cases (34%) were (+), and 83 (66%) were (-). There was no significant association between E-cad or EGFR, and any of the clinicopathologic variables except for an association between EGFR(+) and SCC histologic type. Both negative and cytoplasmic staining of E-cad correlated with shorter patient survival with P=0.008 and 0.002, respectively. EGFR expression did not correlate with patient survival; however, patients with E-cad(-)/EGFR(+) phenotype had poorer survival than those with E-cad(+)/EGFR(-) (P=0.026). Our study suggests that lung AdC and SCC may be stratified based on expression of E-cad and EGFR with the E-cad(-)/EGFR(+) expression having a worse disease outcome. Moreover, the cytoplasmic expression of E-cad may represent an altered localization of this protein in association with tumorigenicity.