Expression Pattern of CXCR4/CXCL12 Is Related to Survival after Hepatic Resection for Colorectal Liver Metastases

Abstract

Introduction: The chemokine network such as interaction between CXCR4 and CXCL12 plays a role in the induction of organ-specific metastases. The present study evaluated CXCR4/CXCL12 expression pattern in colorectal liver metastases (CRLM) and determined whether the expression patterns affect tumor progression. Methods: We examined pattern of CXCR4 and CXCL12 immunohistochemistry in 92 CRLM patients. CXCL12/CD133 immunoreactivity was also evaluated. The median follow-up time of these patients was 38 months. Clinicopathological data of these patients were evaluated. Overall survival rates were evaluated by the Kaplan-Meier method. The expression profile of CXCR4 in the colorectal cancer cell line was determined by fluorescence microscopy. Results: The cytoplasmic CXCR4 expression was greater in 36 patients than that indicated by CXCR4 staining intensity of hepatocytes. CXCL12 was also expressed in hepatocytes surrounding the tumors at high and low levels in 68 (74%) and 24 (26%), respectively. High levels of nuclear CXCR4 expression were observed in 23 patients which significantly correlated with CXCL12 expression in hepatocytes. The nuclear CXCR4 expression in the cancer cell line increased after exposure to CXCL12. The univariate and multivariate analyses demonstrated that high levels of nuclear CXCR4 and the increased CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CRLM. Conclusion: The CXCR4 expression in CRLM together with the upregulation of CXCL12 in hepatocytes may help to predict the clinical outcomes of patients with CRLM after hepatic resection and to determine whether adjuvant chemotherapy may be required.