Genetic tumor markers with prognostic impact in Dukes' stages B and C colorectal cancer patients.
OBJECTIVE
To examine several genetic changes in primary colorectal carcinomas (CRCs) from patients with 10 years of follow-up and associate the findings with clinicopathologic variables.


METHODS
DNA from 220 CRCs were analyzed for allelic imbalances at 12 loci on chromosome arms 1p, 14q, 17p, 18q, and 20q, and the microsatellite instability (MSI) status was determined. The clinical significance of the tumor protein 53 (TP53) mutations was re-evaluated.


RESULTS
Patients with tumors containing 17p or 18q deletions had shorter survival than those without these alterations (P =.021, P =.008, respectively). This was also significant for the Dukes' B group (P =.025, P =.010, respectively). Furthermore, patients with tumors showing losses of both chromosome arms revealed an even poorer disease outcome than those with either 17p or 18q loss. Patients with low increase in 20q copy number in their tumors had longer survival compared with those without changes (P =.009) or those with a high increase of copy number (P =.037). This was also evident for the Dukes' C group (P =.018, P =.030, respectively). MSI was seemingly a beneficial marker for survival (P =.071). A significant association between mutations affecting the L3 zinc-binding domain of TP53 and survival was confirmed in this cohort after 10 years of follow-up, and also was found to apply for patients in the Dukes' B group. Several associations were found among genetic and pathologic data.


CONCLUSIONS
The present study indicates that 17p, 18q, and 20q genotypes, and TP53 mutation status add information in the subclassification of Dukes' B and C patients and may have impact on the choice of treatment.
Diep
Chieu B
CB
Department of Genetics, Institute for Cancer Research, Oslo, Norway.
Thorstensen
Lin
L
Meling
Gunn Iren
GI
Skovlund
Eva
E
Rognum
Torleiv O
TO
Lothe
Ragnhild A
RA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers; D016159:Tumor Suppressor Protein p53