P-0007 - Integrin expression in gastric cancer impacting tumor progression and treatment

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Gastric Cancer
Translational Research
Presenter Mareile Joka
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors M. Joka1, C. Ilmberger2, K. Pietsch3, J. Werner1, B. Mayer1
  • 1LMU University Clinic Munich Department of Surgery, Munich/DE
  • 2Spherotec GmbH, Martinsried/DE
  • 3LMU Munich, Munich/DE

Abstract

Introduction

Metastatic spread of cancer cells is a key event in tumor progression. Identification of the metastasis-driving biomarkers is important in the development of new therapeutic strategies. Integrins are a family of transmembrane glycoprotein receptors that mediate cell-matrix and cell-cell interaction. They are involved in many pathological conditions such as inflammation and tumor progression. This study evaluated the expression of integrins as a prognostic and predictive factor in primary and metastatic gastric cancer.

Methods

Between 2011 till 2013, 94 patients with gastric cancer were immunohistochemically analyzed for integrin expression. Namely, COLR (α2ß1), VitR (α5ß3), LamininR (α6ß1), FibR (α5ß1), VLA4R (α4ß1) were stained in primary gastric tumors and their synchronous metastases (regional lymph nodes n = 32, liver n = 14, peritoneum n = 17). Integrin expression pattern was correlated with clinical and pathological parameters using univariate and multivariate analyses.

Results

Correlation of the different integrin expression pattern on mucosal cells proved a high co-expression of COLR and VitR (p = 0.009). Compared to the corresponding benign gastric mucosa, strong levels (≥50% positive cancer cells) of COLR and LamininR expression were observed on primary tumor cells. Contrary, FibR showed decreased levels (≤50% positive cancer cells) in primary gastric cancer. The expression of COLR on primary tumor cells showed a positive correlation with the R2 stage (p = 0.039), the tumor diameter (p = 0.019) and the pN2 stage (p = 0.039). Strong COLR expression was found in both primary and metastatic tumors. LamininR showed an upregulated expression in distant metastasis (liver, peritoneum) compared to the corresponding primary tumors. LamininR expression significantly correlated with WHO type of adenocarcinoma (p = 0.001) and the intestinal tumor type (p = 0.001). Strong FibR expression was found in the endothelial cells in liver and peritoneal metastases. VLA4 showed no significant correlation in the expression of primary or metastatic tumors.

Conclusion

COLR, LamininR and VitR are involved in the metastatic process. Treatment options in advanced gastric cancer are limited and often associated with side effects resulting in treatment non-adherence. Thus, specific inhibition of metastasis driving integrins with antibodies or small molecules might represent a promising treatment tool in metastatic gastric cancer.