title: Role of oncogenic pathways and KRAS/BRAF mutations in the behavior of colon adenocarcinoma in renal transplant patients.
abstract: BACKGROUND
  The behavior and mechanisms of colorectal carcinoma in solid organ transplantation have not been well characterized. Our aim was to determine the clinical and molecular phenotypes of colorectal carcinoma in kidney transplant recipients and compare with those in the nonimmunosuppressed population. For the first time, we analyzed the impact of KRAS and BRAF mutations in kidney transplantation.
  
  
  METHODS
  Kidney transplant recipients with colorectal carcinoma were diagnosed and followed up from 1992 to 2007. Twelve patients fulfilled inclusion criteria and were matched with the general population with colorectal cancer. To assess the possible mechanisms involved in the clinical behavior of colorectal carcinoma, we compared the tumoral expression by immunohistochemical analysis of molecule markers of mammalian target of rapamycin (mTOR) pathway, angiogenesis and proliferation, and the role of activating mutations in KRAS and BRAF genes.
  
  
  RESULTS
  Colorectal carcinoma was more prevalent and exhibited a trend for worse prognosis in transplant patients. Although the mTOR pathway was activated in both populations, activation was lower in transplant patients because of relatively higher phosphatase and tensin homolog expression in the former. Angiogenesis was activated in colorectal carcinoma in both groups. KRAS mutations were found in transplant recipients treated with calcineurin inhibitors and with high expression of phosphatase and tensin homolog.
  
  
  CONCLUSIONS
  The activation of oncogenic pathways could be responsible for the clinical behavior of posttransplant colorectal carcinoma. The mutation status of the KRAS gene is likely involved in mTOR pathway and to be a prognosis marker for colorectal cancer in kidney transplantation.
authors.affiliation: Renal Transplant Unit, Department of Nephrology and Renal Transplant, Hospital Clinic, Barcelona, Spain. irevuelt@clinic.ub.es
authors.forename: Ignacio
authors.initials: I
authors.lastname: Revuelta
authors.forename: Daniel
authors.initials: D
authors.lastname: Moya-Rull
authors.forename: Adriana
authors.initials: A
authors.lastname: García-Herrera
authors.forename: Jordi
authors.initials: J
authors.lastname: Rovira
authors.forename: Francisco
authors.initials: F
authors.lastname: Ayala de la Peña
authors.forename: Antonio
authors.initials: A
authors.lastname: Misiego
authors.forename: Flavia
authors.initials: F
authors.lastname: Guzmán
authors.forename: Federico
authors.initials: F
authors.lastname: Oppenheimer
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000737:chemistry / Q000235:genetics* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis; D010641:Phenotype; D015995:Prevalence; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D058570:TOR Serine-Threonine Kinases / Q000032:analysis; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D007166:Immunosuppressive Agents; C117307:KRAS protein, human; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C546842:MTOR protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins