Prognostic significance of allelic lost at chromosome 18q21 for stage II colorectal cancer.
OBJECTIVE
Allelic loss of a portion of chromosome 18q and lack of expression of deleted in colorectal cancer (DCC) protein has been reported as an adverse prognostic indicator for stage II (i.e., Dukes' B2) colorectal cancer. Our aim was to assess whether the DCC gene locus was responsible.


METHODS
We amplified five DNA microsatellite markers located on chromosome 18q21 surrounding or within the DCC gene locus, including a DCC intragenic (TA)n microsatellite, from DNA microdissected and isolated from paraffin-embedded, formalin-fixed specimens of 70 patients with stage II colorectal cancer. Epidemiological and survival data were blinded from the microsatellite analysis to avoid bias.


RESULTS
The average follow-up time was 63.3 months for all patients. Eleven patients died of colorectal cancer by the end of the study. Loss of heterozygosity of 18q21 was present in 30 of 70 (43%) tumors. After adjustment for all other evaluated factors, 18q21 allelic loss was not a predictor of survival (hazard ratio, 1.17; 95% confidence interval, 0.27-5.10; P = 0.84).


CONCLUSIONS
Loss of heterozygosity of 18q21 does not seem to predict a survival disadvantage in stage II colorectal cancer in our patient population, and its proposed use as a prognosticator of survival or chemotherapy stratification marker for stage II tumors is not substantiated.
Carethers
J M
JM
Department of Medicine, University of California, San Diego, USA. jcarethers@ucsd.edu
Hawn
M T
MT
Greenson
J K
JK
Hitchcock
C L
CL
Boland
C R
CR
D000368:Aged; D000483:Alleles; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
D004273:DNA, Neoplasm