Dis Colon Rectum  2001 Apr;44(4):549-57 

Prognostic value of K-ras mutations and allelic imbalance on chromosome 18q in
patients with resected colorectal cancer.

Font A, Abad A, Monzo M, Sanchez JJ, Guillot M, Manzano JL, Pinol M, Ojanguren
I, Rosell R.

Laboratory of Molecular Biology of Cancer, Hospital Germans Trias i Pujol,
Badalona, Spain.

PURPOSE: We designed this study to assess the frequency of K-ras mutations in
patients with resected colorectal tumors and their association with survival. A
second objective was to analyze the prognostic value of different K-ras
genotypes. In a subgroup of patients we also investigated the presence of
allelic imbalance on chromosome 18q and its relationship to clinical outcome.
METHODS: One hundred fourteen colorectal tumors resected between 1983 and 1986
were analyzed to detect K-ras point mutations at codons 12, 13, and 61 by
polymerase chain reaction followed by allele specific oligonucleotide
hybridization. A subgroup of 77 tumors was further screened to detect loss of
heterozygosity on chromosome 18q using three polymorphic microsatellite markers
(D18S67, D18S474 and D18S58). RESULTS: K-ras mutations were detected in 29
percent (33/114) of patients. K-ras mutations correlated with age and
preoperative carcinoembryonic antigen levels, and there was some indication that
they may be linked to poor survival, especially in Stage II tumors, where a
subgroup of patients with aspartic and serine mutations showed significantly
reduced survival (P = 0.03) compared with K-ras-negative patients. 18q loss of
heterozygosity was present in 39 percent (25/63) of tumors. A multivariate
analysis of Stage II tumors showed that 18q loss of heterozygosity was
significantly associated with a worse prognosis (P = 0.006). A significant
decrease in survival was identified in ten patients harboring both genetic
alterations (K-i mutations and 18q loss of heterozygosity; P = 0.02).
CONCLUSIONS: In colorectal tumors, K-ras mutations and 18q loss of
heterozygosity are two genetic markers which may identify patients with more
aggressive behavior, mainly in Stage II tumors. These findings warrant further
research, because they can be useful in customizing adjuvant chemotherapy.

PMID: 11330582 [PubMed - indexed for MEDLINE]