Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive human colorectal cancer

Background: Molecular metastases are precursors of postoperative recurrence. 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 analyse if CCR5 expression correlates with the presence hepatic molecular metastases (MM).

Methods: 93 patients undergoing elective surgery for colorectal cancer were assessed. The K-ras mutation status was defined by PCR-RFLP, the CCR5 expression status was analysed 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.