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Erschienen in:
01.07.2011 | Original Paper
Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive human colorectal cancer
Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2011
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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.