Reduced E-Cadherin Expression Is Associated with Increased Lymph Node Metastasis and Unfavorable Prognosis in Non-small Cell Lung Cancer

Abstract

E-cadherin is a calcium-dependent, epithelial cell adhesion molecule whose reduced expression has been associated with tumor dedifferentiation and increased lymph node metastasis in clinical studies involving several carcinomas. In this study, 111 patients who had previously undergone complete resection and systematic mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) were studied retrospectively. In the primary tumor, as well as in the lymph node metastases, E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1; Takara, Otsu, Japan). There was a significant inverse correlation between E-cadherin expression and lymph node stage (Pearson correlation coefficient -0.52, p = 0.0001) as well as tumor differentiation (Pearson correlation coefficient -0.27, p = 0.005). Moreover, Kaplan and Meier survival estimates showed a significant correlation between E-cadherin expression and patient survival in log rank testing (p = 0.006). In the patient group with the highest proportion of E-cadherin positive tumor cells, 60% of the patients were still estimated to be alive at 36 mo, versus 32% of the patients in the group classified as showing negative E-cadherin expression. Our findings provide clinical evidence that reduced E-cadherin expression is associated with tumor dedifferentiation, increased lymphogenous metastasis and poor survival. It seems therefore that E-cadherin expression might be an important prognostic factor in NSCLC.

Clinical application of biological markers for treatments of resectable non-small-cell lung cancers

“…In addition, VEGF-C expression, another member of the VEGF family and reported to induce lymphangiogenesis (Skobe et al, 2001), was also associated with the prognosis of stage I patients, as reported previously (Kajita et al, 2001;Arinaga et al, 2003). Furthermore, previous clinical studies have shown that reduced expressions of several metastatic suppressor genes, including E-cadherin (Sulzer et al, 1998;Liu et al, 2001), MRP-1/CD9, and KAI1/CD82 , are also associated with nodal metastases and a poor prognosis of patients with stage I NSCLCs. Although there were a few wide CIs for the hazard ratios in Table 4, these results might be partly because of factors like differing follow-up.…”

“…For example, the activation of oncogenes or the inactivation of tumour suppressor genes, such as K-ras mutation and p53 mutation, could initially cause malignant progression . In addition, reduced expressions of metastatic suppressor genes, such as E-cadherin (Sulzer et al, 1998;Liu et al, 2001), MRP-1/CD9, and KAI1/CD82 , could induce tumour cells with high metastatic potential. In addition, tumour angiogenesis, affected by various angiogenetic factors such as the VEGF family (Dvorak et al, 1995), is associated with not only tumour growth but also tumour metastasis (Folkman, 1995).…”

“…Owing to developments in molecular biology, many clinical studies on molecular markers associated with tumour biological behaviour have been performed in human cancers, and these molecular markers, including oncogenes, tumour suppressor genes , metastatic suppressor genes Sulzer et al, 1998), and angiogenetic factors (Imoto et al, 1998;Masuya et al, 2001), could be prognostic factors for NSCLC patients. Therefore, to improve the treatment of NSCLC patients, it is important to decide the optimal therapeutic strategy for them according to the tumour biology.…”

“…VEGF-A and VEGF-C are members of the VEGF family associated with angiogenesis or lymphangiogenesis (Dvorak et al, 1995;Skobe et al, 2001). E-cadherin is one of the metastatic suppressor genes (Mbalaviele et al, 1996;Sulzer et al, 1998).…”

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

“…Epithelial cell adhesion molecule is an epithelial differentiation marker, which is frequently expressed on normal epithelial cells (Winter et al, 2003). Loss of Ep-CAM expression is therefore a likely consequence of tumour cell de-differentiation, as for instance is seen for the epithelial differentiation antigen E-cadherin (Sulzer et al, 1998). On the other hand, overexpression or maintenance of Ep-CAM expression on tumour cells relative to normal epithelia may then be an indication that its presence confers a benefit to tumour cells.…”