title: KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis.
abstract: BACKGROUND
  KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status.
  
  
  RESULTS
  KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006).
  
  
  CONCLUSIONS
  Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung.
authors.affiliation: Department of Medical Oncology, La Paz University Hospital, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Cejas
authors.forename: Miriam
authors.initials: M
authors.lastname: López-Gómez
authors.forename: Cristina
authors.initials: C
authors.lastname: Aguayo
authors.forename: Rosario
authors.initials: R
authors.lastname: Madero
authors.forename: Javier
authors.initials: J
authors.lastname: de Castro Carpeño
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Belda-Iniesta
authors.forename: Jorge
authors.initials: J
authors.lastname: Barriuso
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno García
authors.forename: Javier
authors.initials: J
authors.lastname: Larrauri
authors.forename: Rocío
authors.initials: R
authors.lastname: López
authors.forename: Enrique
authors.initials: E
authors.lastname: Casado
authors.forename: Manuel
authors.initials: M
authors.lastname: Gonzalez-Barón
authors.forename: Jaime
authors.initials: J
authors.lastname: Feliu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins