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Chemokine Receptor CCR6 Expression Level and Liver Metastases in Colorectal Cancer

Pirus Ghadjar, Sarah Ellen Coupland, Il-Kang Na, Michel Noutsias, Anne Letsch, Andrea Stroux, Sandra Bauer, Heinz J. Buhr, Eckhard Thiel, Carmen Scheibenbogen, Ulrich Keilholz

From the Departments of Hematology, Medical Oncology, and Transfusion Medicine, Pathology, Cardiology and Pneumonology, and Surgery, Institute for Medical Informatics, Biometry, and Clinical Epidemiology, Charité, Campus Benjamin Franklin, Berlin, Germany.

Address reprint requests to Ulrich Keilholz, MD, Charité, Campus Benjamin Franklin, Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Hindenburgdamm 30, 12200 Berlin, Germany; e-mail: ulrich.keilholz{at}charite.de

PURPOSE: The liver is the primary organ of metastasis in colorectal cancer (CRC). Chemokine receptor CCR6 is expressed on a subset of T cells and is associated with their migration into the liver. This study was performed to analyze a possible association between CCR6 expressed by primary CRC and liver metastases.

PATIENTS AND METHODS: CCR6 expression levels were evaluated by immunohistology in 64 CRC primary tumor specimens. Twenty-four of 64 patients had synchronous liver metastases. Evaluation of immunostaining was performed semiquantitatively by visual assessment and quantitatively by digital image analysis (DIA). Multiple logistic regression analysis was performed to assess relevant parameters for liver metastases.

RESULTS: CCR6 expression was verified in all 64 primary tumor specimens with considerable variations in intensity; 21 tumors (33%) demonstrated weak CCR6 staining, 32 (50%) demonstrated intermediate staining, and 11 (17%) demonstrated strong staining. Quantitative assessment by DIA showed an up to 5-log difference in CCR6 values. CCR6 staining was significantly stronger in tumor cells compared with adjacent colon epithelial cells (P < .0005). Multiple logistic regression analysis, controlling for age, sex, tumor stage, nodal status, pathologic grade, and preoperative carcinoembryonic antigen levels, revealed that CCR6 staining in the primary tumor was independently associated with the presence of liver metastases (odds ratio = 2.1; P = .002).

CONCLUSION: The association between expression level of CCR6 in primary CRC and synchronous liver metastases suggests that CCR6 and its ligand may be involved in the metastatic spread to the liver. Therefore, CCR6 may be a potential target for specific therapeutic interventions.

Supported by a grant from the Charité.

P.G. and S.E.C. share first authorship; C.S. and U.K. share senior authorship.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Chemokine Receptor CCR6 Expression in Colorectal Liver Metastasis
  Claudia Rubie, Vilma Oliveira-Frick, Bettina Rau, Martin Schilling, and Mathias Wagner
  JCO 2006 24: 5173-5174 [Full Text]

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