The Correlation between the Expression of E-cadherin, VEGF-C, VEGF-D and the Real Extent of Lymph Node Metastases using Cytokeratin 18 in Early Gastric Cancer

ABSTRACT

PURPOSE: VEGF-C and VEGF-D are angiogenetic factors, and abnormal expression of E-cadherin hasa role in the progression of gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of E-cadherin, VEGF-C and VEGF-D with the presence of lymph node metastases (LNM) using cytokeratin 18 in early gastric cancer (EGC). MATERIALS AND METHODS: Immunohistochemical staining for E-cadherin, VEGF-C and VEGF-D was performed in 49 EGC patients from March 1997 to December 2002. To evaluate the real extent of LNM, 1,562 lymph nodes from 49 patients were re-examined with the use of cytokeratin 18. RESULTS: Eleven (0.7%) LNM were newly found in 12.2% (n=6) of patients. The real LNM rate was 3.6% in mucosal invasive (m) cancer and 38.1% in submucosal invasive (sm). Stage migration was seen in three patients (6.1%). Abnormal expression of E-cadherin was detected in 36.7% of the patients and expression of VEGF-C and VEGF-D was detected in 16.3% and 36.7% of the patients, respectively. Abnormal expression of E-cadherin was significantly correlated with tumor differentiation (P=0.0103) and Lauren classification (P<0.0001). There was no positive relationship of VEGF-C and VEGF-D expression with the clinicopathological findings for EGC including LNM. However, the frequency of lymph node metastases was significantly higher in patients that demonstrated abnormal expression of E-cadherin with positive immunoreactivity of VEGF-C or VEGF-D (P=0.031). CONCLUSION: In present study, we could not demonstrate a relationship between the presence of LNM and expression of VEGF-C and VEGF-D in EGC. However, VEGF-C or VEGF-D expression, in addition to the abnormal expression of E-cadherin, was correlated with the real extent of LNM in EGC.