Allelic loss of chromosome 18q and prognosis in colorectal cancer.
BACKGROUND
Colorectal cancer occurs in approximately 150,000 people each year in the United States. Prognostic assessment influences the treatment of patients with colorectal cancer, including decisions about adjuvant therapy. We evaluated chromosome 18q allelic loss, a genetic event associated with tumor progression, as a prognostic marker for this disease.


METHODS
We developed procedures to examine the status of chromosome 18q with microsatellite markers and DNA from formalin-fixed, paraffin-embedded tumors. Allelic loss of chromosome 18q was assessed in 145 consecutively resected stage II or III colorectal carcinomas.


RESULTS
Among patients with stage II disease, the five-year survival rate was 93 percent in those whose tumor had no evidence of allelic loss of chromosome 18q and 54 percent in those with allelic loss; among patients with stage III disease, survival was 52 and 38 percent, respectively. The overall estimated hazard ratio for death in patients whose tumor had chromosome 18q allelic loss was 2.83 (P = 0.008) according to univariate analysis. Furthermore, chromosome 18q allelic loss remained a strong predictive factor (hazard ratio for death, 2.46; 95 percent confidence interval, 1.06 to 5.71; P = 0.036) after adjustment for all other evaluated factors, including tumor differentiation, vein invasion, and TNM stage.


CONCLUSIONS
The status of chromosome 18q has strong prognostic value in patients with stage II colorectal cancer. The prognosis in patients with stage II cancer and chromosome 18q allelic loss is similar to that in patients with stage III cancer, who are thought to benefit from adjuvant therapy. In contrast, patients with stage II disease who do not have chromosome 18q allelic loss in their tumor have a survival rate similar to that of patients with stage I disease and may not require additional therapy.
Jen
J
J
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196.
Kim
H
H
Piantadosi
S
S
Liu
Z F
ZF
Levitt
R C
RC
Sistonen
P
P
Kinzler
K W
KW
Vogelstein
B
B
Hamilton
S R
SR
D000368:Aged; D000483:Alleles; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000302:isolation & purification; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000302:isolation & purification*; D004276:DNA, Satellite; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D012091:Repetitive Sequences, Nucleic Acid; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D004276:DNA, Satellite