Microsatellite instability as a prognostic factor in resected colorectal cancer liver metastases.
BACKGROUND
Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are currently recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Untreated CRC hepatic metastases are incurable and are associated with a median survival of 4 to 12 months. Conversely, surgical resection in selected patients results in a 20% to 50% cure rate. The aim of this study was to investigate the prognostic importance of MSI-H in patients undergoing resection of hepatic CRC metastases.


METHODS
DNA was extracted from paraffin-embedded, resected metastatic CRC liver lesions and corresponding normal liver parenchyma from 190 patients. MSI-H status was determined by polymerase chain reaction-based evaluation of the noncoding mononucleotide repeats BAT-25 and BAT-26.


RESULTS
MSI was detected in tumors from 5 (2.7%) of the 190 CRC patients. All MSI-H tumors were in patients with node-positive CRC primary tumors. The median survival after hepatic resection of MSI-H and non-MSI-H tumors was 67 and 61 months, respectively (P = .9).


CONCLUSIONS
These data suggest that MSI-H is not a common feature in resected CRC liver metastases and do not suggest a role for MSI in stratifying good versus poor prognosis in these patients.
Haddad
Riad
R
Sunnybrook and Women's Health Sciences Centre, T-Wing, Room T2-057, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
Ogilvie
Robert T
RT
Croitoru
Marina
M
Muniz
Victoria
V
Gryfe
Robert
R
Pollet
Aaron
A
Shanmugathasan
Preshanthini
P
Fitzgerald
Timothy
T
Law
Calvin H L
CH
Hanna
Sherif S
SS
Jothy
Serge
S
Redston
Mark
M
Gallinger
Steven
S
Smith
Andrew J
AJ
D000368:Aged; D043171:Chromosomal Instability / Q000235:genetics*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis