Journal of Cancer Research and Clinical Oncology, 2011, Vol.137(7), pp.1139-1145
Byline: Carl C. Schimanski (1), Markus Moehler (1), Ines Gockel (2), Tim Zimmermann (1), Hauke Lang (2), Peter R. Galle (1), Martin R. Berger (3) Keywords: CCR5; Chemokine receptor; Colorectal cancer; Liver metastases; Molecular metastases; Micrometastases; Tumor cells Abstract: Background Molecular metastases are precursors of postoperative recurrence, detected by molecular-biological tools. Chemokines and their receptors contribute to dissemination and local immune recognition. A strong expression of the chemokine receptor CCR5 is associated with non-metastatic colorectal cancer and increased CD8+ T-cell infiltration. The aim of this study was to analyze whether CCR5 expression correlates with the presence of hepatic molecular metastases (MM). Methods Ninety-three patients undergoing elective surgery for colorectal cancer were assessed. The K-ras mutation status was defined by PCR--RFLP, and the CCR5 expression status was analyzed by CCR5-specific reverse transcription (RT-PCR) analysis. Liver biopsy samples had been intra-operatively taken to screen for MM. MM were detected by K-ras-specific PCR--RFLP and nested CK20/GCC RT-PCR. Prevalence of MM was correlated with CCR5 expression status. Results Human colorectal cancer harboured K-ras mutations in 53% (codon 12: 47% codon 13: 6%) of cases. Among K-ras mutants, MM were detected in 27--53% of patients, dependent on the technique applied (K-ras-specific PCR--RFLP assay vs. nested CK20/GCC RT-PCR approach (P = 0.004)). CCR5 expression of K-ras mutants ranged from absent (23/49: 47%), weak (17/49: 35%), intermediate (4/49: 8%) to strong (5/49: 10%). MM were found in 30% of CCR5 negative and in 23% of CCR5 positive cancer patients by the K-ras-specific PCR--RFLP assay. The nested CK20/GCC RT-PCR assay detected MM in 87% of CCR5 negative and in 27% of CCR5 positive colorectal cancer patients (P = 0.00002). Conclusion Thus, CCR5 expression of the primary cancer might be a valuable biomarker indicating the absence of hepatic molecular metastases. Author Affiliation: (1) Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101, Mainz, Germany (2) Department of general and abdominal surgery, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101, Mainz, Germany (3) German Cancer Research Center, INF 280, 69120, Heidelberg, Germany Article History: Registration Date: 22/03/2011 Received Date: 24/08/2010 Accepted Date: 22/03/2011 Online Date: 06/04/2011 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00432-011-0980-6) contains supplementary material, which is available to authorized users.
CCR5 ; Chemokine receptor ; Colorectal cancer ; Liver metastases ; Molecular metastases ; Micrometastases ; Tumor cells
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