Clinicopathological significance of E-cadherin, VEGF, and MMPs in gastric cancer

Abstract

E-cadherin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs) are important molecules involved in tumor metastasis. In this study, we examined the expressions of E-cadherin, VEGF, MMP-1, MMP-2, and microvessel density (MVD), as well as microlymphatic vessel density (MLVD) in 200 cases of gastric cancer tissues, and determined the relationship between these parameters and the clinicopathological features and patient survival. Protein expressions, MVD, and MLVD were detected by immunohistochemistry. The correlation between the expression levels of these molecules and the clinicopathological features was analyzed. Patient survival was estimated by Kaplan and Meier analysis. Compared to normal gastric mucosa, expression of E-cadherin was reduced in 78% of gastric cancer tissues and 44.6% of adjacent non-cancerous gastric tissues. VEGF was positive in 81.5% of gastric cancer tissues, 35.7% of adjacent non-cancerous gastric tissues, and 10% of normal gastric mucosa. MMP-1 was positive in 80.5% of gastric cancer tissues, 69.6% of adjacent non-cancerous gastric tissues, and 20% of normal gastric mucosa. Reduced expression of E-cadherin was closely correlated with poor tumor differentiation and a deeper tumor invasion. Increased expressions of VEGF and MMP-1 were closely linked with poor differentiation and Lauren classification. Increased expression of MMP-2 was closely correlated with more lymph node metastasis, a deeper invasion, and a larger tumor size. More MVD was observed in VEGF-positive tissues than in VEGF negative tissues. Therefore, abnormal expressions of E-cadherin, VEGF, MMP-1, and MMP-2 are widely present in gastric cancer tissues. Abnormal expressions of E-cadherin, VEGF, and MMP-2 may represent the early molecular changes in the development of gastric cancer. Positive expression of E-cadherin and negative expression of VEGF and MMP-2 are correlated with a better patient survival.

Overexpression of HOXA10 promotes gastric cancer cells proliferation and HOXA10+/CD44+ is potential prognostic biomarker for gastric cancer

“…Apparently, early diagnosis of its recurrence and metastasis is the biggest challenge in improving the survival of patients with GC. Several potential prognostic biomarkers like CD44 (Chen et al, 2014), HER2 (Gravalos and Jimeno, 2008), P53 (Goncalves et al, 2011), and E-cadherin (Zhou et al, 2010) have been identified. Especially, CD44 expression is associated with lymph node metastasis (LNM), distant metastasis, TNM stage, and poor prognosis of GC (Chen et al, 2014), as CD44 is a cell surface glycoprotein receptor for hyaluronan acid involved in cell adhesion, migration and metastasis of GC cells (Winder et al, 2011).…”

An abnormally high expression of ISL-1 represents a potential prognostic factor in gastric cancer

“…Despite the fact that most cases of early stage gastric carcinoma can be cured by surgical resection, metastasis contributes to the high rate of mortality in gastric carcinoma [7]. Although numerous immunohistochemical markers such as human epidermal growth factor receptor 2, matrix metallopeptidase-2, and epithelium cadherin have been recognized as biomarkers in other types of cancer, these markers are not commonly used to assess biological behavior and prognosis in gastric cancer because of low levels of sensitivity and specificity [8][9][10][11][12][13]. Therefore, there is an urgent need to identify novel prognostic and predictive biomarkers to improve the diagnosis and clinical management of patients with gastric cancer, which in turn may help to develop more effective treatment strategies.…”

Molecular targeted therapies in advanced gastric cancer: does tumor histology matter?

“…Many first-line phase II trials have evaluated cetuximab in combination with various chemotherapy regimens [Pinto et al 2007[Pinto et al , 2009Woell et al 2008;Han et al 2009;Kanzler et al 2009;Kim et al 2009;Lordick et al 2010;Moehler et al 2010] showing an ORR in the range of 40-60%, time to progression 5.5-8 months, and OS 9.5-16 months. However, preliminary results of a randomized phase II study showed no clinically significant benefit when cetuximab was added to docetaxel plus oxaliplatin [Richards et al 2011] [Stein et al 2007;Tebbutt et al 2008;Li et al 2010].…”