The prognostic value of the presence of mutations at the codons 12, 13, 61 of K-ras oncogene in colorectal cancer.
The predictive and prognostic value of the c-K-ras mutation is still unequivocal despite extensive and intensive studies. Investigation of the occurrence of mutations in 88 colorectal cancer patients' specimens using the polymerase chain reaction (PCR) is reported: age: 61.9 years (27-80), gender: 48 male, 42 female, Dukes' stages: 43 at B, 35 at C, 10 at D, primary of tumour: 52 colon, 36 rectal adenocarcinoma. Mutation of one of the three ras-codons was detectable in the 54 cases, more frequently at the Dukes' stage C (p < 0.05). The ras-mutation correlated to a more elevated death-rate in the Dukes' B and C stages (p < 0.01). Mean survival time and time to progression were significantly longer at the Dukes' stage B if mutation was not detected (p < 0.01). The genetic alteration occurred significantly more frequently at tumours of the right-side colon, than the left side (p < 0.02) or rectum (p < 0.05). However, in the age group of 41-50 years, it was more significantly identified in the cases of rectal cancer (p < 0.01). At the age of 51-60 years mutations were detected in men at a higher rate (p < 0.05). The mutation of the codon 13 appeared more frequently in the cases of local recurrences (p < 0.05). The occurrence of the ras-oncogene is a sign of an extremely malignant potential of tumour. This fact manifested itself in the time to progression and mean survival time of patients at the same clinical or pathological stage. The higher frequency of genetic alterations at the proximal colon may be the reason for more unfavourable prognosis of the disease localised to this site. Reconstructing the molecular events, the presence of the ras mutation proved to be an important element for prognosis of the disease and should be a basis of potentially individualised therapeutic intervention.
MI Central Hospital, 2nd Department of Internal Medicine-Oncology, Budapest, Hungary.
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G
Pajkos
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Kiss
J
J
Sándor
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I
Ember
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Kisházi
D014408:Biomarkers, Tumor / Q000235:genetics*; D003062:Codon; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D005260:Female; D011905:Genes, ras; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D003062:Codon; D005819:Genetic Markers