title: Prognostic value of disseminated colorectal tumor cells in the liver: results of follow-up examinations.
abstract: OBJECTIVE
  Dissemination of tumor cells is an initial step in metastatic disease. Detection of disseminated tumor cells (DTC) in blood, bone marrow and lymph nodes has been associated with reduced disease-free survival, but to date there are no data for hepatic DTC. We investigated the prognostic relevance of hepatic DTC that are present in patients with colorectal cancer (CRC) at the time of surgery.
  
  
  METHODS
  In 121 patients with CRC clinically diagnosed for liver metastasis by ultrasound, CT, and exploration during surgery DNA from liver biopsy specimens obtained during surgery was examined by a PCR-RFLP assay for K-ras mutations as a marker for DTC. At the time of surgery 54 of the 121 were mutated in K-ras codons 12 or 13. After a median follow-up of 405 days all survivors were reevaluated by ultrasound/CT.
  
  
  RESULTS
  Patients with a K-ras mutation in their primary tumor had a significantly lower probability of survival and higher risk of harboring a synchronous second colorectal carcinoma than patients with a K-ras wild-type tumor. Based on specimens taken intraoperatively DTC were found in the liver of 14 of 54 patients (26%). At follow-up only 10 of 40 patients (25%) with DTC-free liver had died of their disease but 9 of the 14 patients with hepatic DTC. Among the 14 patients with hepatic DTC 10 (71%) had developed new liver metastasis, compared to 12 of 40 (30%) in those without hepatic DTC.
  
  
  CONCLUSIONS
  Hepatic DTC in colorectal cancer patients is associated with reduced overall survival and increased risk of hepatic metastasis development. Further studies are necessary to corroborate our results since the number of patients studied is still limited.
authors.affiliation: Department of Surgery, Municipal Hospital Nürnberg Nord, Nuremberg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Linnemann
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Schimanski
authors.forename: Christoph
authors.initials: C
authors.lastname: Gebhardt
authors.forename: Martin R
authors.initials: MR
authors.lastname: Berger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000401:mortality* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon