Microsatellite instability and DNA ploidy in colorectal cancer: potential implications for patients undergoing systematic surveillance after resection.
BACKGROUND
Appropriate stratification tools for targeted surveillance after resection for colorectal cancer (CRC) are lacking. The objective of the current study was to investigate the effect of microsatellite instability (MSI) and DNA ploidy on surveillance after surgery.


METHODS
The authors evaluated 186 consecutive, population-based patients with stage I through III CRC who underwent surgery with curative intent and who entered a systematic surveillance program. MSI was analyzed with polymerase chain reaction for 5 known quasimonomorphic markers (BAT-26, BAT-25, NR-21, NR-24, and NR-27), and DNA ploidy was analyzed with automated cytometry. Recurrence, recurrence-free survival (RFS), and disease-specific survival (DSS) were evaluated by univariate and multivariate statistical tests.


RESULTS
Patients with MSI (20%) were significantly younger than patients without MSI (median age, 61 years vs 67 years; P=.016). Proximal location (adjusted odds ratio [AOR], 5.4; 95% confidence interval [95% CI], 2.1-14.1 [P=.001]), large tumor size (>or=5 cm: AOR, 3.5; 95% CI, 1.3-9.6 [P=.015]), and poor tumor differentiation (AOR, 6.6; 95% CI, 2-21.8 [P=.002]) were associated with MSI. MSI conveyed an increased risk for locoregional recurrence (OR, 2.9; 95% CI, 1.2-7 [P=.016]), with a trend toward a shorter time to recurrence (P=.060). Neither MSI status nor DNA ploidy predicted distant metastasis, RFS, or DSS. Lymph node status was the best predictor of distant spread (AOR, 3.9; 95% CI, 2-7.9 [P<.001]) and DSS (hazard ratio, 4.9; 95% CI, 2.6-9 [P<.001]).


CONCLUSIONS
Patients who had microsatellite instable tumors were at increased risk for locoregional recurrence, whereas lymph node status was the best predictor of distant metastasis. Clinical surveillance and choice of modality (ie, endoscopy vs radiologic imaging) may be improved when patients are stratified according to these cancer features.
Søreide
Kjetil
K
Department of General and Gastroenterological Surgery, Stavanger University Hospital, Stavanger, Norway. ksoreide@mac.com
Slewa
Aida
A
Stokkeland
Pål J
PJ
van Diermen
Bianca
B
Janssen
Emiel A M
EA
Søreide
Jon Arne
JA
Baak
Jan P A
JP
Kørner
Hartwig
H
D000368:Aged; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011003:Ploidies; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor