title: Brain metastases from colorectal cancer: risk factors, incidence, and the possible role of chemokines.
abstract: BACKGROUND
  Brain metastases from colorectal cancer (CRC) are uncommon. There has been relatively little published on the host and tumor factors that might lead to this clinical scenario. We reviewed all cases of brain metastases from CRC at Dartmouth-Hitchcock Medical Center over a more than 20-year period to establish incidence and to identify patient and cancer characteristics which were associated with their development.
  
  
  METHODS
  We present a retrospective review of 39 confirmed cases of brain metastases from CRC diagnosed between 1984 and 2006. Immunohistochemical staining for CXCR4 was performed on all available brain metastasis biopsy specimens.
  
  
  RESULTS
  The incidence of brain metastases from CRC was 2.3%. Left-sided primary colon tumors predominated. The majority of patients had pulmonary metastases at the time brain metastases were identified, and those with preexisting pulmonary metastases had progression of that disease. All patients were symptomatic from brain metastases, and the cerebellum was the most common area of brain involvement. Immunohistochemical analysis confirmed strong expression of CXCR4 in all brain metastases sampled.
  
  
  CONCLUSIONS
  The incidence of brain metastases from CRC is low. Primary tumor in the left colon, long-standing pulmonary metastases, especially those with recent progression, and CXCR4 expression by tumor cells are all associated with increased risk of brain metastases. Increased survival among patients with metastatic CRC will likely result in an increased incidence of brain metastases. Further characterization of the role of tumor and host factors might yield better insight into the development, and potentially the prevention, of this devastating situation.
authors.affiliation: Department of Internal Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Mongan
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Fadul
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Cole
authors.forename: Bassem I
authors.initials: BI
authors.lastname: Zaki
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Ripple
authors.forename: Tor D
authors.initials: TD
authors.lastname: Tosteson
authors.forename: J Marc
authors.initials: JM
authors.lastname: Pipas
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D002528:Cerebellar Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000473:pathology / Q000556:secondary; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009513:New Hampshire / Q000453:epidemiology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4