Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 14, 2011; 17(26): 3109-3116
Published online Jul 14, 2011. doi: 10.3748/wjg.v17.i26.3109
Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases
Claudia Rubie, Vilma Oliveira Frick, Pirus Ghadjar, Mathias Wagner, Christoph Justinger, Stefan Graeber, Jens Sperling, Otto Kollmar, Martin K Schilling
Claudia Rubie, Vilma Oliveira Frick, Christoph Justinger, Jens Sperling, Otto Kollmar, Martin K Schilling, Department of General, Visceral, Vascular and Paediatric Surgery, University of the Saarland, 66421 Homburg/Saar, Germany
Pirus Ghadjar, Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, 3010 Bern, Switzerland
Mathias Wagner, Institute of Pathology, University of the Saarland, 66421 Homburg/Saar, Germany
Stefan Graeber, Institute of Medical Biometrics, Epidemiology, and Medical Informatics (IMBEI), University of the Saarland, 66421 Homburg/Saar, Germany
Author contributions: Rubie C and Frick VO contributed equally to this work. Rubie C contributed to study concept and design, and drafting of the manuscript; Frick VO was involved in acquisition of data, analysis and interpretation of data; Wagner M provided technical support; Justinger C, Sperling J and Kollmar O provided material support; Graeber S performed statistical analysis; Ghadjar P and Schilling MK critically revised the manuscript for important intellectual content and provided material support.
Correspondence to: Claudia Rubie, PhD, Department of General, Visceral, Vascular and Paediatric Surgery, University of the Saarland, Chirurgische Klinik, Gebäude 57, 66421 Homburg/Saar, Germany. ca.labor@uks.eu
Telephone: +49-6841-1647869 Fax: +49-6841-1647944
Received: October 21, 2010
Revised: December 17, 2010
Accepted: December 24, 2010
Published online: July 14, 2011
Abstract

AIM: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer (CRC) patients.

METHODS: Using Real Time-PCR, enzyme-linked immunosorbent assay, Western Blots and immunohistochemistry, we have analyzed the expression of CCL20, CCR6 and proliferation marker Ki-67 in colorectal liver metastasis (CRLM) specimens from stage IV CRC patients who received preoperative FOLFOX chemotherapy (n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery (n = 29).

RESULTS: Of the 53 patients who received FOLFOX, time to liver surgery was ≤ 1 mo in 14 patients, ≤ 1 year in 22 patients and > 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery (P < 0.001) in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy.

CONCLUSION: This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.

Keywords: FOLFOX chemotherapy, CCL20/CCR6 expression, Colorectal liver metastases, Proliferation