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

Abstract

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 avidinbiotin complex method and monoclonal antibodies against E-cad and EGFR. Unequivocal membrane staining in 410% 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 ( þ ), 53 (45%) were negative (À); 23 cases of the negative group had only cytoplasmic staining. For EGRF, 43 cases (34%) were ( þ ), and 83 (66%) were (À). There was no significant association between E-cad or EGFR, and any of the clinicopathologic variables except for an association between EGFR( þ ) and SCC histologic type. Both negative and cytoplasmic staining of E-cad correlated with shorter patient survival with P ¼ 0.008 and 0.002, respectively. EGFR expression did not correlate with patient survival; however, patients with E-cad(À)/EGFR( þ ) phenotype had poorer survival than those with E-cad( þ )/EGFR(À) (P ¼ 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(À)/EGFR( þ ) 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.

Prognostic and Clinicopathological Significance of Downregulated E-Cadherin Expression in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

“…22 studies investigated the impact of E-cadherin expression on overall survival (OS) [14]–[21], [23], [25]–[29], [31]–[36], and most of them assessed the clinicopathological parameters at the same time [14]–[20], [25], [29], [31], [33], [35]. Among these 22 studies, 17 studies evaluated patients in Asian [14]–[17], [19], [20], [23], [25], [26], [29], [31]–[36], five studies evaluated patients in Caucasian [18], [21], [27], [28], [30]. The percentage of reduced E-cadherin expression was more than 50% in 12 studies [15], [19], [20], [26]–[30], [32], [36], while 10 studies showed percentage of reduced E-cadherin expression was less than 50% [14], [16]–[18], [21], [23], [25], [33]–[35].…”

Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line

“…EMT, as defined by the combined loss of E-cadherin and the induction of mesenchymal markers (e.g., vimentin), has been reported to be correlated with a poor prognosis for NSCLC patients [37,38]. Some studies showed that the mesenchymal phenotype was more resistant to erlotinib than the epithelial phenotype, suggesting a potential role for EMT as a determinant of sensitivity to erlotinib [25,26].…”

Paradigm of kinase-driven pathway downstream of epidermal growth factor receptor/Akt in human lung carcinomas

“…In our study, such a trend was not found (data not shown); however, a correlation between Akt activation and nodal metastasis was found when NSCLC cases were viewed as a whole. As a possible underlying mechanism, Akt is known to reduce E-cadherin expression in NSCLC [29]. Because this correlation was not observed within each histological type, we next examined mTOR, as a candidate mediator of metastasis and found a correlation between high p-mTOR and nodal metastasis in SCC.…”