CXCR4 Expression in Gastric Cancer and Bone Marrow: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells, and Patients Survival

Dmitry Osinsky,Sergej Merentsev,Lesya Mamontova,Larissa Bubnovskaya,Lilya Gumenyuk,Irina Ganusevich,Sergej Osinsky,Antonina Kovelskaya

doi:10.1155/2015/980214

Abstract

Aim. The analysis of the association of CXCR4 expression in gastric cancer (GC) and bone marrow (BM) with clinical characteristics. Patients and Methods. 65 patients with GC were investigated. Immunohistochemistry, immunocytochemistry, NMR-spectroscopy, and zymography were used. Results. CXCR4 was expressed in 78.5% of GC specimens and correlated with tumor hypoxia (P<0.05), VEGF expression (P<0.01), and gelatinases activity (P<0.05). CXCR4-positive cells in GC were detected in 80% of patients with disseminated tumor cells (DTCs). Overall survival (OS) of patients with CXCR4-positive tumors was poorer than that of patients with CXCR4-negative tumors (P=0.037). The CXCR4-positive cells in BM were found in 46% of all patients and in 56% of patients with DTCs. CXCR4 expression in BM was not associated with OS. Risk of unfavourable outcome is increased in patients with CXCR4-positive tumors (P<0.05). CXCR4 expression in BM was positively associated with DTCs, especially in patients with M0 category. Risk of unfavourable outcome is increased in patients with M0 category and with both CXCR4-positive BM and DTCs (P=0.03). Conclusions. CXCR4 expression in tumor was positively correlated with hypoxia level and VEGF expression in tumor as well as OS. CXCR4 expression in BM is associated with DTCs.

Highlights

CXCR4 is a chemokine receptor specific for stromal-derived factor-1 (SDF-1 called CXCL12) with potent chemotactic activity for lymphocytes
CXCR4-positive cells were found in 78.5% of gastric cancer patients and 21.5% of patients were negative for CXCR4
We have not found the strong association between CXCR4 expression in tumor and clinicopathological characteristics, it may be paid attention to the more number of adenocarcinomas, tumors with grade G3 as well as with nodal involvement and M1 category in the cases with CXCR4-positive tumors

Summary

Introduction

CXCR4 is a chemokine receptor specific for stromal-derived factor-1 (SDF-1 called CXCL12) with potent chemotactic activity for lymphocytes. Andre et al [14] have shown that CXCR4 expression was not associated with clinical characteristics of breast cancer, and it was not prognostic factor for overall survival, but significantly higher risk for bone metastasis in patients with CXCR4-positive tumors which was observed. Lee et al [16] have shown that strong CXCR4 expression was significantly associated with lymph node metastases and higher stages III/IV and further tended to be correlated with a reduced 5-year survival rate. Patients with nuclear CXCR4 expression have a better overall survival, cytoplasmic pattern of CXCR4 expression tends to be associated with a shorter overall survival than nuclear staining In this context it has to be noted that Spano et al [26] have indicated strong nuclear staining of CXCR4 in 29.8% of patients with early stage nonsmall-cell lung cancer and a significantly better outcome in this case. Preliminary results of our study were recently presented in abstract form

Patients and Methods

Results

Discussion