BC 03. CXCR4/CXCL12 and CCL2 Is a Promising Predictive Marker for Survival after Hepatic Resection for Colorectal Liver Metastases


H. Yoshida, N. Sakai, H. Kohno, H. Shimizu, M. Ohtsuka, Y. Yoshitomi, M. Miyazaki

Chair(s): Mustafa Cikirikcioglu, Frank Dor, René Tolba, David J. Hackam, Cliff Shearman, Modise Koto

13:50 - 14:00h at Erszebet Room (A)

Categories: ESSR Best Clinical Research Paper, Surgical Oncology

Session: ESSR Best Clinical Research Paper


Invited discussant: Osman Yuksel, Attila Szijártó, Lázár György, Gokhan Yagci, Mihály Boros, Thomas Hubert


Background
Liver metastases often occur in patients with colorectal cancer. The chemokine network such as interaction between CXCR4 and CXCL12 and CCL2 plays a role in the induction of organ-specific metastases. The present study examined CXCR4/CXCL12 axis and CCL2 in colorectal liver metastases (CRLM).

Material and Methods
We identified 92 CRLM patients whose tumors were evaluated by CXCR4, CXCL12 and CCL2 immunohistochemistry. Immunoreactivity for CXCR4 was semi-quantified by assessing staining intensity. CXCL12/CCL2 immunoreactivity was semi-quantified by assessing the staining intensity and ratios (%) of positively stained cells. Clinicopathological data of these patients were examined. Overall survival rates were evaluated by the Kaplan-Meier method. The expression profile in the colorectal cancer cell line was determined by fluorescence microscopy.

Result
The cytoplasmic CXCR4 expression was greater in 36 patients than that indicated by CXCR4 staining intensity of hepatocytes. The CXCL12 was also expressed in hepatocytes surrounding the tumors at high and low levels in 68 (74%) and 24 (26%). High levels of nuclear CXCR4 expression were seen in 23 patients, correlated with CXCL12 expression in hepatocytes. The nuclear CXCR4 expression in the cancer cell line increased after exposure to CXCL12. CCL2 expression was correlated with microvessel density. Higher levels of nuclear CXCR4, the increased CXCL12 expression in hepatocytes, and lower CCL2 expression were significantly better prognostic factors for overall and hepatic disease-free survival.

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.