Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer.
OBJECTIVE
The survival of stage II colorectal cancer (CRC) patients is approximately 70% at 5 years. Identification of the patient subgroup at high risk for tumour recurrence and death would allow more informed use of chemotherapy for this stage of disease. Several clinical and pathological factors have been reported to associate with worse survival. In the present study we investigated the prognostic significance of two major genetic alterations in CRC: microsatellite instability (MSI+) and the type of Ki-RAS mutation.


METHODS
PCR-based molecular techniques were used to screen for MSI+ and Ki-RAS mutation in 396 stage II CRC patients with an average follow-up time of 75 months. Clinicopathological information was obtained by retrospective review of pathology reports.


RESULTS
Prominent vascular invasion was identified in 19% of cases and was found to be an independent prognostic factor for poor outcome (relative risk = 2.08, 95% confidence interval: 1.22-3.57, p = 0.008). The MSI+ phenotype was found in 23% of proximal tumours and Ki-RAS mutations in 38% of the overall series. Neither MSI+ nor the type of Ki-RAS mutation showed prognostic significance in this cohort of stage II CRC.


CONCLUSIONS
MSI+ and Ki-RAS mutation type are not useful markers for the identification of high-risk stage II CRC patients. Further prospective and/or cohort studies are required to determine whether these molecular changes have predictive value for survival benefit from 5-fluorouracil-based adjuvant chemotherapy.
Wang
Cathy
C
School of Surgery and Pathology, University of Western Australia, Nedlands 6907, Australia.
van Rijnsoever
Marius
M
Grieu
Fabienne
F
Bydder
Sean
S
Elsaleh
Hsny
H
Joseph
David
D
Harvey
Jennet
J
Iacopetta
Barry
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013997:Time Factors
D000970:Antineoplastic Agents