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

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.

• Authors: Carl C Schimanski, Markus Moehler, Ines Gockel, Tim Zimmermann, Hauke Lang, Peter R Galle, Martin R Berger
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 137 Issue 7 Pg. 1139-45 (Jul 2011) ISSN: 1432-1335 [Electronic] Germany
• PMID: 21468700 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• DNA, Neoplasm
• KRAS protein, human
• Keratin-20
• Proto-Oncogene Proteins
• RNA, Messenger
• RNA, Neoplasm
• Receptors, CCR5
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Aged
• Biomarkers, Tumor (genetics)
• Colorectal Neoplasms (genetics, pathology)
• DNA, Neoplasm (genetics)
• Female
• Humans
• Keratin-20 (genetics)
• Liver Neoplasms (genetics, secondary)
• Male
• Middle Aged
• Mutation (genetics)
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Prognosis
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins p21(ras)
• RNA, Messenger (genetics)
• RNA, Neoplasm (genetics)
• Receptors, CCR5 (genetics)
• ras Proteins (genetics)