Am J Gastroenterol  2000 Oct;95(10):2953-7 

Impact of KRAS and TP53 mutations on survival in patients with left- and
right-sided Dukes' C colon cancer.

Bleeker WA, Hayes VM, Karrenbeld A, Hofstra RM, Hermans J, Buys CC, Plukker JT.

Department of Surgery, Medical Genetics and Pathology, University Hospital
Groningen, The Netherlands.

OBJECTIVE: It has been suggested that KRAS and TP53 mutated tumors might
influence the phenotypic behavior of left- and right-sided colon tumors. We
investigated the incidence of these mutations in left- and right-sided colon
tumors and their possible influence on survival in a homogeneous group of
patients with Dukes' C colon cancers. METHODS: The primary tumors of 55 patients
with a sporadic Dukes' C colon cancer, all treated with adjuvant chemotherapy
were analyzed for the presence of KRAS and TP53 mutations. Mutation detection of
the KRAS and TP53 genes was performed on paraffin-embedded tumor material, using
denaturating gradient gel electrophoresis. The 5-yr survival rates of KRAS and
TP53 mutated tumors were analyzed regarding right-sided tumors (defined as
tumors up to the splenic flexure) and left-sided tumors (defined as tumors from
the splenic flexure to the rectosigmoid peritoneal reflection). RESULTS: KRAS
mutations occurred more frequently in the right colon compared to the left colon
(R = 38% (10/26); L = 10% (3/29); chi2 test: p = 0.014). KRAS mutations did not
influence survival in patients with right-sided colon tumors. Patients with KRAS
mutation-negative tumors in the right colon, however, had a significantly worse
survival than patients with left-sided KRAS mutation-negative tumors (5-yr
survival; R: 34% vs L: 65%, log-rank test: p = 0.007). TP53 mutations of a
possible causative nature were found in 24 tumors (44%). Neither the incidence
(R = 42% (11/26); L = 45% (13/29)) nor the survival of TP53 mutated tumors
differed significantly between left- and right-sided tumors. Furthermore,
survival of patients with TP53 mutation-negative tumors did not differ
significantly between left- and right-sided tumors. CONCLUSIONS: There seems to
be no difference in survival rate between patients with KRAS mutated and KRAS
negative Dukes' C colon tumors; however, KRAS mutations are more frequently
found in the right colon compared to the left colon. TP53 mutations do not have
predominance for either side of the colon, and there are no differences in
survival in patients with left-sided versus right-sided tumors. Patients with
KRAS-nonmutated tumors in the right colon did have a worse survival compared to
those with such tumors in the left colon. This suggests that other genetic
factors may play a role in tumor genesis in this subgroup of patients.

PMID: 11051374 [PubMed - indexed for MEDLINE]