K-ras mutations and prognosis in large-bowel carcinomas.
BACKGROUND
Colorectal carcinogenesis is regarded as a multistep process involving several genetic alterations, with mutation in the K-ras gene in about half of the tumours. We aimed at clarifying the role of this genetic alteration related to survival and clinicopathologic variables.


METHODS
One hundred large-bowel carcinomas operated on between 1978 and 1982 were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene, using enriched polymerase chain reaction amplification, restriction fragment length polymorphism analysis, and direct sequencing.


RESULTS
Forty mutations were found (40%): 31 in codon 12 and 9 in codon 13, 7 different types. There was no relationship between tumours with and without K-ras mutations with regard to Dukes' stages, age or sex of the patient, tumour localization, histologic grade, DNA ploidy pattern, HLA-DR staining pattern, or survival. Samples from 5 different localizations in 7 carcinomas showed identical K-ras mutation pattern, as did 19 recurrences/ metastases originating from 11 carcinomas.


CONCLUSIONS
When present, the primary tumour shows homogeneous distribution of K-ras mutation, and the mutation follows the carcinoma in the secondary deposit, regardless of lymphogenous or hematogenous spread. The presence of K-ras mutation does not seem to have prognostic significance for the patient, and the precise nucleotide change is furthermore not predictive of tumour behaviour.
Andersen
S N
SN
Institute of Forensic Medicine, National Hospital, University of Oslo, Norway.
Løvig
T
T
Breivik
J
J
Lund
E
E
Gaudernack
G
G
Meling
G I
GI
Rognum
T O
TO
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009367:Neoplasm Staging; D017354:Point Mutation; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis