Microsatellite instability did not predict individual survival of unselected patients with colorectal cancer.
BACKGROUND
High microsatellite instability (MSI-H) occurs in about 15% of colorectal cancers (CRC) and clinical as well as pathological features differ from tumours exhibiting low microsatellite instability (MSI-L) or microsatellite stability (MSS). Conflicting data exists about the relevance of MSI in predicting the prognosis and benefit of 5-fluorouracil (5-FU) based chemotherapy in patients with CRC. We investigated the usefulness of MSI as a predictor of distinct clinical attributes influencing recurrence rate and disease-free survival (DFS) subject to the use of adjuvant or palliative chemotherapy with 5-FU in stage II- stage IV CRC.


METHODS
We collected data and tumours of 416 consecutive stage I to IV CRC patients from 2000 to 2002, and followed them for a median time of 33 months. Microsatellite loci recommended by the National Cancer Institute were analysed. Cox proportional hazard modelling was used to compare clinical data and survival as well as associations for MSI and 5-FU treatment status of patients with MSI-H, MSI-L or MSS CRC.


RESULTS
We identified 52 MSI-H (13%), 21 MSI-L (5%) and 343 MSS (82%) tumours. CRC with MSI-H tended to have a decreased likelihood of metastasising to regional lymph nodes (p=0.055), whilst age of diagnosis and tumour location did not differ. In an analysis that did not take into account the use of chemotherapy, univariate and multivariate analyses failed to show a difference between MSI-H and MSS groups with respect to disease-free and overall survival. Furthermore, survival under application of 5-FU did not correlate with MSI status.


CONCLUSIONS
No clear influence of MSI status on overall survival and response to 5-FU chemotherapy was found.
Lamberti
C
C
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. christof.lamberti@ukb.uni-bonn.de
Lundin
S
S
Bogdanow
M
M
Pagenstecher
C
C
Friedrichs
N
N
Büttner
R
R
Sauerbruch
T
T
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil