title: 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).
  
  
  CONCLUSIONS
  Thus, CCR5 expression of the primary cancer might be a valuable biomarker indicating the absence of hepatic molecular metastases.
authors.affiliation: Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101, Mainz, Germany. schimanski@1-med.klinik.uni-mainz.de
authors.forename: Carl C
authors.initials: CC
authors.lastname: Schimanski
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.forename: Ines
authors.initials: I
authors.lastname: Gockel
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Martin R
authors.initials: MR
authors.lastname: Berger
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D053554:Keratin-20 / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D053554:Keratin-20; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019713:Receptors, CCR5; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins