Involvement of K-RAS mutations and amino acid substitutions in the survival of metastatic colorectal cancer patients.
The efficacy of epidermal growth factor-targeting therapies has been found to be limited in tumors with the wild-type K-RAS gene, suggesting a predictive value of K-RAS gene analysis in tumoral response. However, the prognostic value of K-RAS is controversial. This study included patients diagnosed with metastatic colorectal cancer. The presence of K-RAS mutations was analyzed, and the tumors positive for a K-RAS mutation were further analyzed to identify the mutation type. Similarly, the following clinical and pathological variables were also collected. The study was composed of 53.3 % of patients with wild-type K-RAS and 46.7 % of patients with mutated K-RAS (mutated codon 12 was the most frequent). With a mean follow-up of 15 months (range, 1-45), the median survival of patients with wild-type K-RAS was 31.6 months. The median survival was 24.8 months for patients with K-RAS mutated in codon 12 and 17.8 months for patients with mutated codon 13 (p = 0.37). In a univariate analysis, K-RAS was associated with stage IV at diagnosis (p < 0.005). When K-RAS was mutated, a lower overall survival was observed in cases of G → A transition compared with G → T transversion (19.5 vs. 24.2 months, respectively; p = 0.47). When the amino acid change resulted in an acidic substitution, survival was lower, but it increased when the substitution resulted in a polar or nonpolar amino acid (19.5 vs. 23.2 vs. 24.4 months, p = 0.79). The type of K-RAS mutation or amino acid changes may have prognostic implications in metastatic colon cancer patients. Further research is needed in patients treated in prospective controlled trials.
Oncology Department, Hospital Costa del Sol, Autovia A-7, Km 187, 29603 Marbella, Spain. elperu@hcs.es
Elisabeth
E
Pérez-Ruiz
A
A
Rueda
T
T
Pereda
J
J
Alcaide
D
D
Bautista
F
F
Rivas-Ruiz
R
R
Villatoro
D
D
Pérez
M
M
Redondo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins