Counting alleles to predict recurrence of early-stage colorectal cancers.
BACKGROUND
Chromosome imbalances occur in many cancers and represent important biological properties of tumours. However, measurements of such imbalances are difficult. We used a new, quantitative approach to investigate the prognostic value of chromosome imbalances in early-stage colorectal cancers.


METHODS
We studied 180 patients with no evidence of lymph-node or distant metastases at the time of surgery. DNA from paraffin-embedded tumours was tested for imbalances of chromosome 8p and 18q by digital SNP (single-nucleotide polymorphism)-a technique in which each allele in a sample is directly counted. Surviving patients had median follow-up of 68 months, and disease recurrence was used as the clinical endpoint.


RESULTS
Tumours were divided into three groups: "L" tumours (n=93) had allelic imbalances of chromosomes 8p and 18q, "L/R" tumours (n=60) had allelic imbalances of either chromosome 8p or 18q but not both, and "R" tumours (n=27) retained allelic balance for both chromosomes. 5-year disease-free survival was 100% (95% CI 80-100) for patients with R tumours, 74% (61-87) for patients with L/R tumours, and 58% (47-69) for those with L tumours. These differences were significant (p<0.0001) and were independent of other variables--eg, Duke's stage A tumours of class L were much more likely to recur than Duke's stage B tumours of class R (p=0.002).


CONCLUSIONS
In patients without metastasis, allelic imbalance is a better predictor of prognosis than histopathological stage.
Zhou
Wei
W
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Goodman
Steven N
SN
Galizia
Gennaro
G
Lieto
Eva
E
Ferraraccio
Francesca
F
Pignatelli
Carlo
C
Purdie
Colin A
CA
Piris
Juan
J
Morris
Robert
R
Harrison
David J
DJ
Paty
Philip B
PB
Culliford
Al
A
Romans
Katharine E
KE
Montgomery
Elizabeth A
EA
Choti
Michael A
MA
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
D000368:Aged; D022981:Allelic Imbalance; D002887:Chromosomes, Human, Pair 18; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015996:Survival Rate
D005819:Genetic Markers